Building early relationships: a gamechanger for pioneering rare disease treatment

Advocacy groups play a crucial role in both driving access to innovative treatment and services and educating patients and caregivers on novel breakthroughs.

On average, it takes more than four years to receive an accurate diagnosis of a rare disease.1 This diagnostic odyssey has pushed patients and caregivers online to self-diagnose and learn more about their symptoms. Patients and their loved ones wish to give a name to their symptoms and to attempt to derive sense from a long and often conflicting diagnostic journey and identify potential treatments or options for themselves.

The internet has emerged as an important tool in supporting patients and physicians through the management of rare diseases. Patient Advocacy Groups such as Genetic Alliance (UK) and National Organisation for Rare Diseases (US) have a large online presence and offer support to patients, friends, families, and treating physicians.2,3

Patient Advocacy groups do not just publish website content, but many disease specific groups also have a sizeable social media following. Many patients and family members join closed groups through Facebook and other social media platforms to connect with other patients from all over the world, for example the Keratoconus Facebook group has over 23.4K members from all over the globe.

Dedicated channels like the subreddit R/Haemophilia connect patients and combat the sense of isolation that can be common to sufferers of a rare disease. During the COVID-19 pandemic, these forums have become vital lifelines for patients and their caregivers, who are often shielding to protect themselves or their loved ones from the virus.4Ultimately, this has led to tight-knit and vocal rare disease communities who are motivated and have the potential to shape policy and encourage innovation.

One group excelling in this space is the Genetic Alliance. The group is working with the government department Public Health England to shape the future of care for rare disease patients in the UK. Their work ranges from developing new services in partnership with the National Health Service (NHS) to working with the All Party Parliamentary Group on Rare, Genetic and Undiagnosed Conditions, and the Department of Health on the UK Strategy for Rare Diseases.2

Advocacy groups like the Genetic Alliance have become a supporting voice for rare disease patients and play a crucial role in both driving access to innovative treatment and services and educating patients and caregivers on novel breakthroughs.2

Why is engaging with the community important? And when should this take place?

Listening to the community early on is vital for deeply understanding the patients and their caregivers, as well as healthcare professionals and other stakeholders they interact with on their diagnosis and treatment journey.5,6

Armed with these insights, life sciences companies can develop patient-centric solutions that will lead to more successful products. Taking an engaged approach has clear benefits, including improved trial retention and development of PROs that can support market-entry and market access. Importantly, you can ensure product and service messages are relevant to patients and add value, driving competitive advantage in increasingly crowded landscapes.

One mistake many life science organizations make is waiting until it’s too late to really start listening to both patient and scientific communities. However, we have found that working with these groups during the design of the clinical trial is far more beneficial. By building trust early on, the patients will feel part of the solution from the outset, and communities may begin to work alongside pharma to support the acceptance and approval of new products.

According to one study by The Economist Intelligence Unit Committee, therapies with a patient-centric trial design were 41% more likely to be added to the payer formulary because drugs that used this approach were 90% more likely to be launched than those that were not. The study also showed taking a patient-centric approach to drug development had a significant impact on the likelihood of launch success across oncology, neurology, and of course, rare disease.7

Therapies with a patient-centric trial design were 41% more likely to be added to the payer formulary.

However, life sciences companies do not just need to engage the patients early on. Gaining input from key opinion leaders (KOLs) is also highly beneficial to the drug development process. Identifying a KOL steering committee both increases engagement and ensures the voice of the customer is considered, from R&D to commercialization. The committee, which should consist of established and up-and-coming KOLs, then becomes the golden thread uniting the medical and commercial teams in one voice and purpose.

Several digital tools are available to help uncover the influencers in each community. Digital Opinion Leader (DOL) mapping helps brands to learn about key communicators in the field online, including patient advocates, established KOLs, and rising stars. It involves conducting research to understand who these influencers are and mapping the depth of their influence in the rare disease community. 

Once the company has identified DOLs, it can connect the insights to the brand strategy. Adopting a hybrid approach, mixing online and traditional KOL engagement will help identify opportunities to shape brand perceptions in new markets where pharma companies and lean biotechs may have a limited market presence.

Read the full article here

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Pulse Infoframe Releases Registry for Patient Advocacy Groups

Launching a rare disease patient registry often requires patient advocacy groups to design a registry themselves or pay for an expensive customized solution. With the launch of Rare Central™, Pulse Infoframe offers patient advocacy groups an on-ramp to collecting real-world data, including natural history data, disease-specific data, and patient-reported outcomes. As a patient group’s needs grow and evolve over time, Rare Central’s three levels of entry offer partners the ability to scale data collection to support a wide range of research objectives as their needs become more complex.

Dr. Femida Gwadry-Sridhar, CEO of Pulse Infoframe, says, “Patient groups are experts in their disease and are at the forefront of grassroots operations. They’re best placed to co-design evidence generation solutions that are meaningful to their communities.”

Rare Central was purpose-built for patients and patient advocacy groups. It provides a cost-effective, real-world data collection solution for patient groups looking to accelerate global research into therapeutic treatments for rare diseases.

Collaboration: The Foundation of Rare Central

Alongside its support for research carried out by patients, advocacy groups, pharmaceutical companies, and academic medical centers, Rare Central also enables scientists and researchers to study deidentified data across a family of diseases with the appropriate governance structure and data sharing in place. By leveraging a shared data infrastructure, Rare Central gives researchers data that can be used to advance treatment options within and across therapeutic classes.

Because of the financial and time constraints smaller advocacy groups face when trying to establish registries, they are often excluded from the larger research picture. This makes it difficult to compete with other organizations who are campaigning for researchers and funders to help them discover life-changing treatments.

Rare Central aims to change that, because it can connect patients around the world.

“This makes it a viable option even for smaller patient groups who represent some of the rarest diseases in the world and have been historically unable to commit to a registry,” says Gwadry-Sridhar. “And as the needs of these small groups change, Rare Central is designed to change with them.”

How Rare Central Works

Rare Central is split into three tiers patient advocacy groups can move between at a pace that suits them. This allows organizations with little knowledge of registries to begin collecting quality, regulatory-grade, real-world data at a pace they can manage and then grow as they learn and as resources become available to them, without moving to a new platform.

The Starter tier is perfect for groups beginning their registry journey. It helps establish an initial patient registry on a limited budget, including a contact database, diagnostic information, quality of life surveys. It can help administrators monitor recruitment progress, and patients can track how they are doing.

The Accelerated tier is ideal for organizations supporting a broader set of patient-reported and disease-specific variables, including natural history data. Researchers can use additional tools, such as pre-defined reporting and demographic query functionality, to dive deeper into the rea-world data they have collected via Rare Central Accelerated.

The Advanced tier supports organizations with a need to combine patient-reported data with data entered by clinicians. With a broader set of variables Rare Central Advanced supports multi-site and disease-specific patient registries and natural history data. Researchers can use the information to help better target drug development and to support clinical trials.

A Decade of Experience

Gwadry-Sridhar founded Pulse Infoframe to fill a research gap that neglected millions: an inability to collect standardized, useful real-world evidence in rare disease, cancer, and chronic condition populations. Since 2011, the company has been designing solutions that accelerate rare disease research and create lasting inter-sector partnerships across the globe.

To date, Pulse Infoframe has supported the launch of 70+ registry sites and data hubs, covering more than 25 diseases, working with 10+ industry partners, and supporting the writing of 220 peer-reviewed publications.

Collecting sensitive medical data requires a platform that follows stringent regulatory guidelines. Pulse Infoframe’s solutions comply with all necessary regulations so patient advocacy groups can collect patient data securely, no matter where in the world the patients live.

Patient Advocacy Groups Have a Partner with Pulse Infoframe

Education and support are needed to make disease registries successful. When patient groups work with Pulse Infoframe, they have access to in-house experts who specialize in these areas:

  • evidence strategy and analytics
  • patient insights and engagement
  • patient-reported outcomes
  • language services
  • strategic regulatory services
  • pharmacovigilance
  • risk management

In other words, Pulse Infoframe provides patient groups’ registries the best chance of having real influence on research. Additionally, Rare Central addresses the needs of patients by providing an easy-to-use interface that simplifies the data input process. This, which has benefits for patients with motor skill issues. Lastly, and the patient dashboard allows them patients to track their condition over time.

Rare Central Also Benefits Researchers and Sponsors

For medical facilities and researchers, working with groups using Rare Central brings with it the ability to develop biomarkers and endpoints such as treatment effectiveness and symptomatic events. In addition, researchers can develop evidence to support further research and publications.

Rare Central also benefits sponsors and the wider pharmaceutical industry. For example, it can help increase recruitment for clinical trials, support identification of molecular compounds, and allow sponsors to leverage natural history as comparator arms for platform trials. Pulse Infoframe’s expert in-house teams will also provide additional support with marketing and public relations.

A Special Program for Patient Advocacy Groups and Foundations

Pulse Infoframe is currently seeking to partner with an initial group of patient advocacy groups and research foundations. The early adopters participating in the Rare Central Pioneer Program will receive waived or discounted fees for the first year along with training and support from Pulse Infoframe’s in-house experts. During this year, each group can begin building a portfolio of evidence that can attract new stakeholders and funders to support expansion.

In 2021, Pulse Infoframe heads into its second decade with a focus on expanding their real-world data collection efforts in 20 rare diseases, across four rare disease families. For more information on Rare Central and Pulse Infoframe, visit or email [email protected].

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Unpacking rare diseases in the first edition of Delta magazine

Welcome to Delta – the new Fishawack Health magazine.

We’ve chosen to focus our first edition of the magazine on a topic close to our hearts, rare diseases.

Rare diseases represent an incredibly high unmet need, not only due to the lack of therapies and the practical difficulties in diagnosis, but also in patients’ desire for better knowledge, communication, and more meaningful relationships with their healthcare professionals.

As our rare disease specialist agency Dudnyk says: “We are seeing a growing separation between healthcare professionals and patients. The impact of this great divide in understanding is negatively affecting the treatment experience—for both sides—as well as severely limiting the trajectory of specialty healthcare brands.”

The dynamic between patients and healthcare professionals, combined with the challenges of patient identification and data generation in tiny patient populations (made even more challenging in a global pandemic), means rare disease drug development and launch requires a unique business model.

In this edition of Delta, our consultants, creatives and medical communications experts explore the challenges and opportunities for life science companies operating in rare disease, including:

  • Navigating real-world evidence and why it could be a gamechanger in rare disease
  • A patient’s account of living with a rare disease in the COVID-19 pandemic
  • How to make an impact in small patient populations
  • The lessons Dan Zaksas, PhD, Senior Vice President, Director of Scientific and Medical Affairs at Dudnyk, has learned during a decade working in rare diseases
  • Why you need to build relationships with KOLs and patients much earlier than you think
  • The lasting implications of COVID-19 on the life science industry.

We hope you enjoy the first edition of Delta. If you would like to find out how we can help you solve a specific life science challenge, get in touch with [email protected]


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Real-world evidence: breaking boundaries in rare disease

The COVID-19 pandemic has added a new layer of complexity to the drug development process. Launch timelines have been delayed and clinical trials have been postponed or suspended. As a result, life sciences companies are turning to novel methods of collecting clinical data and innovative trial design.

The generation of data to show the significant benefits of a drug has always been a complex, intricate process, but essential to ensure a product’s approval, support the overall value proposition of the product, and ensure launch success.

The maze of expensive clinical trials a life science company must navigate to reach that approval stamp takes an estimated average of 6-7 years, with a success rate (from clinical testing to approval) of less than 12%.

Although the FDA has noted that the development of and access to rare disease treatments remains a top priority during the pandemic, generating data for these conditions is still highly challenging.

Traditional randomized clinical trials (RCTs) are considered the gold-standard for evidencing the efficacy and safety of a product. However, small patient populations, the high unmet need, and difficulties identifying a control group make it difficult to conduct an RCT when trialling a rare disease therapy. In cases of fatal diseases, recruiting a control arm is also considered unethical.

To solve this challenge, life sciences companies are factoring in additional considerations when generating clinical data.

Sonal Bhatia, Vice President, Medical Affairs Rare Disease at Pfizer, explains that real‑world evidence (RWE) provides a useful way of overcoming some of these challenges.

She says: “A randomized clinical trial is not always going to be a feasible way to address a research question in rare disease because there’s typically a smaller community of patients. When it comes to rare disease, you need real-world evidence.”

However, we are just starting to understand the power of RWE and many stakeholders, including payers, HTA bodies and healthcare professionals, remain unsure of how to navigate the data. As a result, there are several barriers life science companies need to overcome to benefit from RWE in clinical and commercial settings.


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Research shows gene therapies can offer cost savings potential of up to $1.8M over five years for patients with certain blood diseases

A recent analysis by Health Advances looks at two particularly burdensome hematological (or blood) diseases — beta thalassemia and hemophilia A — and finds that potential gene therapies in the pipeline could reduce per patient costs by as much as 41% and 90%, respectively, over five years. Research-based knowledge gained in recent years about the genetic foundation for these diseases has facilitated the pursuit of several promising gene therapy approaches.

bluebird bio to split into oncology and gene therapy specialists

US biotech bluebird bio has announced plans to split into two this year, with a separate oncology business spinning off as the company prepares to bring its products to market.

Under the plans the company’s rare disease drugs will remain under the aegis of bluebird with current genetic disease president Andrew Obenshain taking the reins as CEO.

Meanwhile the as-yet unnamed oncology company will spin off under the leadership of bluebird’s current chief executive Nick Leschly.

Leschly will also take the role of executive chair at bluebird, according to a company statement.

While bluebird has conducted pioneering work in gene therapy for blood disorders and in cancer cell therapy, products have been delayed by issues with filing data for the FDA.

Late last year, bluebird’s shares tanked after the FDA laid out additional manufacturing standards for its lead gene therapy product, Lentiglobin, in sickle cell anaemia that could hold up filing until late 2022.

Bluebird’s lead CAR-T cancer cell therapy idecabtagene vicleucel (ide-cel) was last year hit with an FDA refuse-to-file letter, which required additional data on chemistry, manufacturing and controls before reviewing the company’s dossier.

That made things difficult for development partner Bristol-Myers Squibb, which inherited the drug previously known as bb2121 through its acquisition of Celgene late in 2019.

The FDA is now due to make a decision on ide-cel as a treatment for multiple myeloma in late March.

Laying out the rationale for the spin-off, bluebird said that operating individually the two companies will be more effective at allocating capital.

The companies will be better equipped to deliver on goals and operations will be streamlined and simplified.

They will also be better at raising money with tailored investment theses and increased strategic flexibility.

The gene therapy firm will be focused on its most important therapies in beta-thalassemia, cerebral adrenoleukodystrophy and sickle cell disease in the US And Europe.

Zynteglo is already in beta-thalassemia in Europe, where the company will seek to expand access despite its hefty $1.8 million price tag.

On the oncology side, bluebird has also strengthened its board with the appointment of Dr Ramy Ibrahim, a high-profile leader in clinical development in immunotherapy and cell therapy.

Ibrahim is currently serving as a consultant for the Parker Institute for Cancer Immunotherapy (PICI) and built the clinical capabilities within the institute.

Ibrahim also worked as vice president and global therapeutic head for immuno-oncology at AstraZeneca and MedImmune, helping to develop the immunotherapy Yervoy (ipilimumab) at Bristol-Myers Squibb.

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Tay-Sachs and rare disease registries – the Health Heroes podcast

Episode four of Kantar Health’s Health Heroes podcast tackles pharma’s rare disease challenges, the role of patient registries and hears a moving story about the rare genetic disorder Tay-Sachs disease.

Joining me for this instalment of Health Heroes are Geneviève Bonnélye-Fesnien, global head of real-world evidence, research and consulting at Kantar Health, and Dan Lewi, co-founder of The Cure & Action for Tay-Sachs (or CATS) Foundation.

Dan’s eldest daughter Amelie was diagnosed with Tay-Sachs in 2011 at 15 months of age and he shares the emotional story of caring for her and how that led to setting up The CATS Foundation.

This episode of the podcast also looks at how the GM2 Disease Registry, managed by The CATS Foundation with support from Kantar Health, and it will help both patients and the pharma companies working on treatments for them.

The podcast finishes up with an overview from Geneviève on the current outlook for rare diseases.

The Health Heroes podcast series aims to inform and educate life sciences companies on ways for getting closer to patients to help drive improved health outcomes.

Previous episodes have covered the impact of a rare disease, learning from China’s COVID-19 experience and the coronavirus pandemic’s effect on mental health in the US.


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Operationalize: Expanded Access Programs Summit

Say Goodbye to the Worry & Uncertainty of Setting Up & Managing an Expanded Access Program

This inaugural Operationalize: Expanded Access Programs digital event is here to bring you solutions.

Dealing with a diverse and confusing global regulatory landscape, on top of an increasing number of access requests from patients, is no easy feat for people working in expanded access programs. As operational obstacles can arise at any time, from set up to close out, all stakeholders must equip themselves with the knowledge and tools to overcome these challenges.

By bringing together the world’s leading Expanded Access Programs thinkers, this exclusive platform will clarify the complex issues through end-to-end Managed Access/Compassionate Use program operationalization. Through open discussion, sharing best-practice case studies, and removing hypotheticals, this event provides an unrivalled opportunity to solve your challenges across the entire timeline.

Whether it’s Expanded Access ProgramsEarly Access,Managed AccessCompassionate UseNamed Patient Programsor even Post-Trial Access, ensure you aren’t repeating past mistakes by hearing global leaders recall their experience with a shared goal of providing you with pragmatic solutions to solve these complex hurdles.
Download the Full Event Guide to see what experts from Novartis, Stealth Bio, Santhera, Roche and Janssen will be discussing.

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Rocket Pharmaceuticals in orbit after gene therapy read-out

Shares in Rocket Pharmaceuticals have been living up to their name, shooting up following encouraging early-stage clinical trial results from a gene therapy for a serious inherited rare heart disease.

Results came from a phase 1 trial of RP-A501 for treatment of Danon Disease and sent shares up 75% on the Nasdaq to more than $56, a five-year high.

The surging stock price indicates the market’s confidence in gene therapy products after the successful launch of products such as Roche/Spark Therapeutics’ Luxturna, a gene therapy for a rare inherited eye disease.

Danon Disease is a rare X-linked disorder caused by genetic mutations in the LAMP2 gene and the therapy works by instructing the body to express a healthy copy of the LAMP2B protein in order to correct the condition.

The disease that affects boys and men more severely causes accumulation of autophagosomes – tiny structures that cause cells’ internal structures to break down – in the heart muscle and other tissues.

Together with a build-up of glycogen this can lead to severe and frequently fatal degradation of the heart muscle.

RP-A501 could be the first gene therapy for the disease and the early data showed a positive increase in cardiac protein expression.

As of November, three patients have been treated with a low dose of the therapy and two have been treated with a high dose.

An early trial readout showed two patients with LAMP2B expression that was 50% more than normal, measured nine and 12 months after treatment.

A 15%-20% increase could lead to clinically meaningful improvements in cardiac function and the trial reported a 50% decrease in a key biomarker of heart failure.

There was also a reduction in myocardial cell disarray and a visible reduction in autophagic vacuoles, a hallmark of the disease.

The company also noted stabilisation of three other measures – a heart failure biomarker known as BNP,  plus levels of transaminases and creatine kinase that also indicate skeletal and heart muscle damage.

However one patient who received the highest dose and had a degree of immunity to the adeno-associated virus used in the therapy had an immune reaction classified as a serious adverse event.

Rocket said the event was likely due to complement activation, resulting in reversible thrombocytopenia and acute kidney injury requiring a short round of haemodialysis.

The patient returned to baseline within three weeks and regained normal kidney function.

Dr Barry Greenberg, director of the Advanced Heart Failure Treatment Program at UC San Diego Health, Professor of Medicine at UC San Diego School of Medicine, and the principal investigator said: “Children with Danon Disease live with a heavy disease burden. Young boys are often severely afflicted.

“They show evidence of early onset skeletal muscle weakness and heart disease that can progress rapidly to end-stage with death occurring on the average before age 20. A heart transplant can be performed but is not curative and is associated with its own significant problems.

“The results-to-date for this first investigational gene therapy for monogenic heart failure show the potential for direct clinical benefit without emergence of unanticipated side effects of therapy.”

The company has also begun a stock offering of $175 million in shares to fund further development following the results.






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The urgent need for education and awareness about mitochondrial disease

Delayed diagnosis, misdiagnosis, and no cure or disease modifying treatments – children living with mitochondrial disease face all the issues often associated with rare diseases. It’s a problem that Michelle Bamber, whose two little girls both have the life-limiting condition, knows only too well.

Lily was a happy, contented baby, and her parents had no cause for concern until she went for her two-year check and was put on a pathway to diagnosis.

She is now 11, “healthily unhealthy”, and has just started secondary school. On the surface things are going well, but it has been a difficult journey for the family.

“Lily was a normal baby, and she met all the normal milestones,” says Michelle. “It was only when she was coming up to two that that we started to see issues that we weren’t really happy with.

“There was a delay in getting her two-year check, but when we did, she was referred to the Child Development Centre.”

Initially, they were told Lily probably had cerebral palsy, but as she continued to develop her healthcare team decided she needed further assessment. What followed was a litany of tests and invasive procedures as doctors tried to get to the bottom of her symptoms.

Michelle said: “She was walking, then she had a CT scan, and stopped walking. That obviously rung alarm bells. She had a lumbar puncture, a muscle biopsy, various scans. She had three general anaesthetics in the space of seven weeks.

“The internet told us some very disturbing things: that my child wouldn’t live past the age of five or that children don’t really live longer than two years after diagnosis”

“In August 2011, they said it was a form of mitochondrial disease, but didn’t know what one at that point. They just said it was a neurodegenerative, progressive disease, very similar to Parkinson’s.”

Lily was kept in hospital for a week where she was treated with IV vitamins, then the family were discharged with no further information.

“It was a total shock. We were just sent away from the hospital; we did not know anyone else who had it and we were very much in the dark about what was going to happen. We were on our own,” says Michelle.

“Where do you turn apart from Google? The internet told us some very disturbing things: that my child wouldn’t live past the age of five or that children don’t really live longer than two years after diagnosis.”

Priceless support

It was at this point that Michelle discovered Lily’s Foundation, a patient advocacy group established by Liz Curtis in memory of her own Lily, who died from mitochondrial disease at just eight months old.

Through the foundation, which Michelle actively fundraises for, the Bambers have met other families who are affected by mitochondrial diseases and have been able to access evidence-based information and support.

Mitochondrial disease, or ‘mito’, is an umbrella term for a group of medical disorders caused by mutations in the mitochondria, or the cell “powerhouses”, she explained.

The genetic condition affects different people in different ways, and the symptoms might include seizures, fatigue, vision and hearing loss, cognitive disabilities, respiratory problems, and poor growth. It can affect any of the body’s organs and systems, including the brain, heart, lungs, gut, liver, and skin. Crucially, there is no cure, and while work is ongoing to develop pioneering genetic therapies, the current standard of care relies heavily on symptom management.

That’s what makes the support provided by Lily’s Foundation invaluable, says Michelle, who explained that Willow, who was born in 2013, had been diagnosed at just four months in part due to the family’s new-found awareness of the signs.

“Usually, the foundation put on family weekends so all the families can come together. The kids go off and have fun with the volunteers at the kids’ clubs.

“The parents have lectures from the mitochondrial specialists and get all the latest advice and news on what’s happening in the medical world.”

Extended support

While the charity has not been able to host such events during the COVID-19 pandemic, it has been able to offer support to many more families thanks to a sudden uptick in awareness.

Back in May, the son of long-standing Coronation Street characters Leanne Battersby and Steve McDonald, Oliver, was diagnosed with mito after suffering seizures.

“That’s, obviously, creating a good bit of awareness and phone calls to the Lily Foundation have really increased. More people have been welcomed into the Lily family and are not living on their own with whatever their child’s going through anymore,” says Michelle.

She also hopes the storyline, which the charity and specialist doctors were consulted on, will help to address a lack of awareness among healthcare professionals that can often result in delayed or incorrect diagnosis.

“A lot of people report that they are having seizures and are diagnosed with having epilepsy, for example. Sometimes it can take a long time to get to that bigger picture and see that a patient has this, this, and this and that it is all because of mitochondrial issues,” Michelle explains.

Asked what parents who suspect their child has a rare disease like mito should do in this situation, Michelle said they should “trust their gut”.

“If you think there’s an issue, then keep talking to the doctors. Unfortunately, a lot of people find that they’re not listened to – they have to keep going back and keep insisting that things aren’t right,” she says.

For more information about the Lily Foundation, click here.

Cambridge Rare Disease Network Exploring Rare Diseases is produced in partnership with Cambridge Rare Disease Network (CRDN). CRDN is building a vibrant network of patients and stakeholders to share knowledge and foster innovation that leads to better diagnosis, treatment and support for those living with a rare disease.

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‘Knowledge is power’ for rare diseases and NAbs

Cure Rare Disease’s Rich Horgan discusses the importance of preclinical NAbs screening and helping rare disease patients better understand their eligibility for gene therapies.

Neutralising antibodies (NAbs) present a unique challenge to researchers looking to treat patients with AAV treatment. As AAV is a virus derived from the common cold, the immune system can easily have levels of pre-existing NAbs that will recognise and neutralise AAV, rendering it ineffective.

In serious cases, higher levels of pre-existing NAbs can even cause a dangerous immune reaction when such therapies are administered.

This is particularly pertinent in rare diseases, as a number of gene therapy products use viral delivery methods to deliver the transgene to target organs.

“NAbs are antibodies that are part of the humoral response of the adaptive immune system,” explains Rich Horgan, founder and president of Cure Rare Disease (CRD), a nonprofit biotech developing CRISPR therapeutics for Duchenne muscular dystrophy (DMD). “They defend against foreign pathogens or infectious particles, and are specific to the targeted antigen, neutralising its effect and rendering it no longer pathogenic by binding to it.

“The goal is to not have the body neutralise the therapeutic, and therein lies the issue with NAbs. For gene therapy treatments using viral delivery methods such as AAV, NAbs are an issue that we must all contend with for both initial patient dosing as well as subsequent redosing.

“Our belief is that patients should understand the challenges associated with drug development and how those challenges impact them personally… It is emotionally challenging for patients who must put their faith in the hands of pharma companies”

“Regardless of route of administration, the virus can be identified as a foreign pathogen causing the adaptive immune system to try and eliminate it through NAbs or other means.”

A further issue is that patients can, and do, develop NAbs from environmental exposure. For example, since AAV is derived from a common virus, patients can develop NAbs against AAV from common colds or other infections – and ultimately, even low levels of antibodies can prevent successful transduction of a viral-based therapeutic.

Clinical trials will screen potential patients for NAbs against the delivery vector to understand the level of NAbs present in the patient (known as the titer level) before dosing them with the experimental drug – but there is currently no standardisation for measuring NAb titer levels in a patient, and each pharma company develops their own assay for testing.

“Moreover, there is not a generally agreed upon threshold for a dose/no-dose decision,” says Horgan. “Ultimately, titer levels are related to safety, as dosing a patient who has a higher titer level (however that may be defined) is more likely to trigger an immune response to the treatment, an extreme example being the infamous case of Jesse Gelsinger.

“As additional gene therapy trials advance, it is important that bodies like the FDA begin to standardise NAb measurement assays and acceptable titer levels for inclusion in clinical trials.”

But although companies are able to screen patients in an attempt to avoid complications, only those already in line for clinical studies qualify, even though for many patients it’s critical to know this information in advance as they consider potential trials.

“To date, there hasn’t been a widely available mechanism for patients and patient families to get insight into whether or not they have a significant level of NAb activity other than through enrollment in a clinical trial,” says Horgan.

Because of this, Horgan believes there needs to be more conversations surrounding this issue, and much more education of patient communities regarding the issue of NAbs and the challenges they create towards participation in a gene therapy study.

“Our belief is that patients should understand the broad challenges associated with drug development and how those challenges may impact them personally. While drug development is technically challenging, it is even more emotionally challenging for patients and patient families who must put their faith in the hands of pharma companies to develop effective treatments for their disease.

“Given the rise of many gene therapies, especially those in the rare disease space, neutralising antibodies stand as a significant challenge to the patient community and it is critical that patients understand that a) these neutralising antibodies exist and can potentially prevent patients from participating in a gene therapy clinical trial and b) collaborative development efforts are needed to ensure that patients can get access to life-saving gene therapies if they possess a significant level of NAbs.”

As such, CRD has rolled out a new system to allow patients to get an understanding of where their neutralising antibody levels stand – knowing that these levels may change over time and that medical decisions should not be based on these results.

The system offers community access to preclinical neutralising antibodies screening. CRD enrolls patients into their research study, then sends a patient kit for local blood collection through a lab. Patients are then informed of the research results several weeks later, and are provided genetic counselling to understand and emotionally handle the results.

“We’ve gone to great lengths to provide a high level of counselling as we know, from personal experience, the results are more than data points – they are the hopes and dreams of a family counting on a potentially life-saving gene therapy,” says Horgan.

“Ultimately, we believe that patients should have knowledge of the impact of neutralising antibodies and must advocate for the advancement of technologies so that all patients may be eligible for viral-based therapeutics. Time and access are of the essence.”

Horgan says that the long-term benefits for families who choose to get screened comes from this generated knowledge.

“Knowledge is power. While the information provided does not change the reality of the situation, we hope that it encourages families to ask more questions and to advocate for the development of technologies to enable dosing with a viral-based therapeutic.

“While non-viral gene therapies will someday be possible, leading researchers believe it will be a number of years before this is realistically feasible.

“Moreover, we want to help patients avoid the immense emotional disappointment of a situation where the patient is found to be ineligible for a gene therapy study due to NAbs even though they never knew that NAbs were an issue to begin with.

“By rallying together a community, we can catalyse the development of technologies to enable dosing (and re-dosing) of advanced therapeutics so that all have access.”

About the interviewee

Rich Horgan is the founder and president of Cure Rare Disease. He has a deep passion for Duchenne muscular dystrophy (DMD) and other rare diseases. With a younger brother impacted by DMD, Rich has a strong interest in accelerating promising treatments for the disease. He has formed a collaboration with world-class researchers and clinicians to pioneer the rapid development of customised therapies for Duchenne and other rare diseases.

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How the rare disease community has developed fertile ground for progress

Amanda Barrell explores how a perfect storm of changing economics, advances in technology, and the increasing volume of the patient voice is stoking change in the rare disease space.

New models of drug development are fuelling life-changing advantages in the rare disease space, previously an economic no-go area for pharma and biotech companies.

That was among the discussion points during Fighting Rare Diseases – The Science, Economics and the Patients, a webinar hosted by o2h Group.

Chairing the event, the company’s Prashant Shah, said: “Rare disease, by definition, means it affects a fairly small number of patients. But the economics are beginning to change, the return on investment is changing, and there is a lot more interest now.

“There are more organisations coming into play and patient groups and charity groups are becoming ever more active. I think there’s more hope for those suffering from rare disease than ever before.”

The interplay between technological advances, new models of drug development, and an increase in patient centricity, has created fertile ground for progress, the panel said.

“Partnering with patient groups has really been our superpower from the beginning, because they are the experts”

Michael Binks, vice president of Rare Disease Research at Pfizer, said: “There’s been a growing awareness of the magnitude of the unmet need, that there are 7,000 identified diseases…and very few therapies available for the majority of them.

“Key factors have been the emergence of communities around some of these diseases that have driven major legislative change and ensured that regulators are more flexible.”

This shift in the regulatory environment has made developing medications for the 300-500m people affected by rare disease globally more economically feasible, said Binks, whose company is focusing on gene therapies in the rare disease space.

Shifting tide

There’s never been a better time for rare disease patients, said Tim Guilliams, CEO of AI-powered biotech company, Healx, who believes that technology such as machine learning (ML) is enabling researchers to take a new view on drug development

His company’s approach is to work with patient groups to understand unmet needs, then use ML to identify existing drugs that could tackle that need and bring them to trial.

“Drug discovery is really hard, and ML is not a magic wand. It’s really just bringing that component to the table to try to move as quickly as you can to get treatments into the clinic,” he said, adding that the method also needed the input of “amazing” pharmacologists, clinical experts, and patient advocates.

“Partnering with patient groups has really been our superpower from the beginning, because they are the experts,” he said.

Return on investment

Shah asked Binks and Guilliams if this paradigm shift in terms of patient involvement was contributing to higher returns on investment in clinical trials.

“It’s hard to put an absolute number on, because each disease has different endpoints, different number of patients that you can enrol, etc. but yes, we believe we can get the cost of clinical trials down significantly because of our model,” said Guilliams.

Binks said that working with patients early on could cut overall costs by reducing the likelihood of study failure.

“Running high-quality clinical trials is expensive. It is sometimes made more expensive by the frequency of failure because we don’t have an adequate understanding of the patient population or the disease.

“Bringing the patients and their families into the conversation early does help to define the clinical development path.”

Market research

Nicola Miller, editor-in-chief at Rare Revolution Magazine and co-founder and trustee of the Teddington Trust for those affected by Xeroderma Pigmentosum, said it made perfect business sense to involve patients in drug development early on.

For a start, she said, there is an assumption within the research community that everyone with a rare disease is seeking a curative treatment, yet many people accept their condition as part of who they are.

“We have all heard stories of where scientists have gone down a particular route, but they haven’t actually thought of engaging with the population as to what is the most debilitating part of their condition,” said Nicola.

“They could be developing something for photo sensitivity for a particular condition, for example, but generally people can cope with that, what they don’t want is a neurological decline which is going to impact their life.”

While some organisations were working well with patient groups, others appeared to be involved in more of a “box ticking operation” which doesn’t benefit anyone, she went on.

“There are huge sums of money and huge amounts of technology being ploughed into this area at the moment, so let’s make sure it’s going into the most beneficial point for the patients,” she said.

Rare future

All three panellists agreed that there was an abundance of hope on the horizon for people living with rare diseases – so long as the whole community continues to work together to overcome the challenge.

“So many things are moving in the right direction: diagnosis, possible treatments, technology, and empowerment. It’s really incredible what is happening in this space now because that just wasn’t the case 20 years ago,” said Guilliams.

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FDA approves Alnylam’s ultra-rare disease drug Oxlumo

The FDA has approved Alnylam’s gene silencing drug Oxlumo, the first treatment for primary hyperoxaluria type 1 (PH1), an ultra-rare and life-threatening genetic disorder.

Oxlumo (lumasiran) was also approved in the European Union last week, making it the third from Alnylam’s pipeline of RNA interference therapeutics to make it to market.

The approval will mean that Alnylam has a clear run at this small but potentially profitable niche market, as the nearest rival from Dicerna is further back in the pipeline.

Patients with PH1 produce far too much oxalate, a substance consumed in food and produced by the body.

This combines with calcium to cause kidney stones and deposits in the kidney, which can lead to kidney failure and the need for dialysis.

As the kidney function worsens, oxalate can build up and damage other organs including the heart, bones and eyes.

The disease is also difficult to diagnose and often takes around six years before doctors correctly identify it.

Oxlumo works by targeting hydroxyacid oxidase 1 mRNA that codes for the enzyme glycolate oxidase.

Preventing the body from producing this enzyme has the knock-on effect of reducing the synthesis of oxalate.

There was no immediate announcement from Alnylam about pricing – but it’s likely to be eye-watering given the rarity of the condition.

Alnylam’s Givlaari, FDA-approved a year ago for acute hepatic porphyria, costs $575,000 per year at full price in the US, although after discounts the figure is more likely to be in the region of $442,000 per year.

In Europe, the company said it will reach separate pricing deals with each member state as quickly as possible.

Although the company has broken new ground with its technology, it is not yet profitable and saw its losses increase in Q3 to more than $253 million, worse than last year’s Q3 loss of $208.5 million.

Alnylam is hoping that revenue will stream from its new products and payments from Novartis, which owns the rights to cholesterol lowering drug inclisiran.

Alnylam licensed inclisiran to The Medicines Company, which was bought last year by Novartis for $9.7 billion.

The Swiss pharma’s bet looks to have paid off as inclisiran is likely to be approved in Europe in the coming weeks after backing from CHMP regulators last month.

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FDA to expedite development of two Sanofi rare disease drugs

The FDA has agreed to expedite development of two rare disease drugs from Sanofi.

The most significant of the two announcements is the Priority Review for avalglucosidase alfa, a potential new therapy for Pompe disease.

The review period will be shortened from the standard ten months to six months or less, and the French pharma said the FDA will make the regulatory decision before May 18th.

These faster reviews are reserved for drugs that could be a significant improvement in safety or efficacy over standard care.

Avalglucosidase alfa is an investigational enzyme replacement therapy designed to improve the delivery of acid alpha-glucosidase (GAA) enzyme to muscle cells.

The FDA will review data from the phase 3 COMET trial in patients with late-onset Pompe disease.

Also in the file will be data from the phase 2 mini-COMET trial testing safety and efficacy in patients with infantile-onset Pompe disease previously treated with standard enzyme replacement therapy, alglucosidase alfa.

European regulators began their review of the data last month.

Pompe disease is caused by a genetic deficiency or dysfunction of the lysosomal enzyme GAA, which results in build-up of complex sugars (glycogen) in muscle cells throughout the body.

The accumulation of glycogen leads to irreversible damage to the muscles, including respiratory muscles and the diaphragm muscle supporting lung function, and other skeletal muscles that affect mobility.

In a separate announcement, Sanofi said the FDA granted Fast Track Designation for its oral investigational Bruton’s tyrosine kinase inhibitor rilzabrutinib, which is in development for immune thrombocytopenia.

Fast Track designation gives developers more support from the FDA for potentially important new drug for serious conditions and can lead to a Priority Review if clinical trial data looks promising enough.

Fast-tracked drugs can also be granted a tentative Accelerated Approval based on earlier data, with a full approval granted on the basis of information from a larger trial.

Sanofi has already begun a phase 3 trial of rilzabrutinib in the disease caused by destruction and impairment of platelet production by the immune system following supportive phase 1/2 results.

Rilzabrutinib is being investigated in a phase 3 trial for pemphigus, an immune mediated disease characterized by blisters in mucous membranes and skin. Sanofi has also begun a phase 2 study in the autoimmune condition IgG4 disease.

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Sanofi/Alnylan’s haemophilia drug hits another safety speed-bump

Sanofi’s attempt to take on Roche with a ground-breaking approach to treating haemophilia has hit a setback after the company voluntarily placed its late-stage trials of fitusiran on hold because of safety issues.

The news that phase 3 development has been put on hold was not announced by the French pharma, but in a joint statement from three haemophilia patient groups.

Sanofi’s management has highlighted fitusiran, a potential competitor to Roche’s haemophilia A drug Hemlibra, as one of the most important drugs in its pipeline.

Fitusiran is being developed for haemophilia A and B in partnership with RNA interference (RNAi) specialist Alnylam – but has already been affected by safety issues.

Alnylam temporarily halted a phase 2 trial in 2017 after a blood clot killed a patient but research resumed in late 2017 after the FDA and Alnylam agreed on new clinical risk mitigation measures.

In a joint statement the World Federation of Hemophilia, the European Haemophilia Consortium and the National Hemophilia Foundation said Sanofi had voluntary put the full development programme on hold “due to the identification of new adverse events”.

In a research note a team of analysts from Jefferies said that fitusiran is unlikely to make difference to Sanofi’s bottom line but could be a “key catalyst to invigorate belief” in the company’s drug pipeline.

According to Jefferies the trial was put on hold to allow investigations of “non-fatal thrombotic events” on 30 October.

Jefferies said it remains unknown if these events are treatment-related or reflect existing illnesses in patients.

The safety events were perhaps compounded by COVID19, which has been associated with abnormal blood clotting in some serious cases.

In the note the Jefferies team led by Peter Welford said that “a setback would likely be perceived negatively for sentiment, particularly as belief in the pipeline is beginning to be built.”

This is likely a reference to Sanofi’s success with Dupixent (dupilumab), developed in partnership with Regeneron for disease including asthma and eczema, which has helped revive the company’s fortunes since a first approval in 2017.

Alnylam’s RNAi technology uses small interfering RNA molecules to target strings of defective RNA molecules in cells, preventing them from coding disease-coding proteins.





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Calliditas plans to file rare kidney disease drug Nefecon after phase 3 success

Swedish biotech Calliditas has announced plans to file its rare disease drug Nefecon with the FDA early next year following positive results from a phase 3 clinical trial.

The company has been developing Nefecon to treat the primary IgA nephropathy, a rare disease that affects the kidney but is caused by overproduction of antibodies produced in the lining of the small intestine, for which there are no approved medications.

Approval by the FDA would give Calliditas a clear shot at the market for the disease affecting 130,000-150,000 people in the US, although US biotech Aravive has a potential competitor in mid-stage clinical development.

Calliditas said part A of the global phase 3 NeflgArd clinical trial has met its target, measuring the effect of Nefecon versus placebo in patients with the disease known as IgAN for short.

Nefecon is a formulation of the established immunology drug budesonide, which targets the Peyer’s patches that are over-active in patients with IgAN.

The antibodies produced as a result lodge in the kidneys, causing severe complications.

The trial met its primary objective of demonstrating a statistically significant reduction in urine protein creatinine ratio (UPCR) or proteinuria after nine months of treatment with 16 mg of Nefecon compared to placebo, with significant continued improvement at 12 months.

The primary endpoint analysis showed a 31% mean reduction in the 16 mg arm versus baseline, with placebo showing a 5% mean reduction versus baseline, resulting in a 27% mean reduction at 9 months of the 16 mg arm versus placebo.

The 199-patient trial also met the key secondary endpoint showing a statistically significant difference in estimated glomerular filtration rate or eGFR after 9 months of treatment with Nefecon compared with placebo.

The eGFR endpoint showed a treatment benefit of 7% versus placebo at nine months, reflecting stabilisation in the treatment arm and a 7% decline of eGFR in the placebo arm.

Collectively the efficacy data from nine months treatment with 16 mg of Nefecon indicated a significant and beneficial effect on key factors correlated to the progression to end stage renal disease (ESRD) for IgAN patients, the company said.

The results indicate that Nefecon was generally well-tolerated and were consistent with the known safety profile of Budesonide. The number of withdrawals in the trial was significantly less than what was seen in the Phase 2b NEFIGAN trial.

Calliditas plans to file for an accelerated approval based on these early results with the FDA in the first quarter of 2021.

A filing for a conditional approval with the European Medicines Agency will follow in the second half of next year.

If approved, Calliditas aims to market Nefecon for IgAN by itself in the US and through collaborations in other regions.

Both of these approvals will require confirmatory data from a larger set of patients for the drug to remain on the market permanently.

Calliditas is led by CEO Renee Aguiar-Lucander and has funded development of Nefecon following an $81m IPO in 2018.

Aguiar-Lucander said in a statement: “Calliditas has been a pioneer in IgAN for many years and we are excited to be the only company to have reported out a positive phase 3 trial in this indication. This result brings hope to thousands of patients who today have no approved treatment alternatives.”

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After two decades, NICE begins consultation on drug assessment methods

The UK’s drug cost-effectiveness body NICE has launched a public consultation, presenting the case for change about how it assesses medicines, medical devices and diagnostics.

NICE has been assessing medicines for 21 years using the Quality Adjusted Life Year (QALY) – the cost to ‘buy’ a patient a year of quality life – as its main methodology.

Big pharma was never going to be happy about the existence of a body like NICE, which is designed to drive down prices paid by the taxpayer-funded NHS, by far and away the largest payer in the UK.

While industry has begrudgingly found ways to work with NICE to get drugs to the UK market, there have been numerous occasions where manufacturers have felt short-changed by the process and in some cases seen drugs failing to get funding on technicalities.

It’s still true that most drugs are eventually funded after a NICE assessment.

But the consensus is that despite tweaks to the system over the years, reform is needed to keep apace with developments in fields such as cancer.

NICE uses the Cancer Drugs Fund to provide interim reimbursement for cancer drugs that require more survival data and allows more flexibility for drugs used at the end of life.

And the cost-effectiveness threshold of £30,000 per QALY has not moved since NICE began, meaning that manufacturers’ wiggle-room on pricing has been constantly squeezed by inflation.

NICE’s consultation will ask whether additional factors should be included in decision-making, such as the severity of a condition and how health technologies can reduce health inequalities.

It is also asking whether there should be more flexibility in rare diseases, where generating evidence is difficult.

NICE wants feedback on how it assesses highly innovative technology, or those with potentially large benefits where risks could be managed.

The consultation will cover the role of evidence gathered outside clinical trials, such as real-world evidence and how NICE could refine its approach to measuring health-related quality of life in different circumstances.

NICE’s consultation follows an internal review of its number-crunching following commitments made in the voluntary pricing scheme that the government agreed with industry last year.

Steve Bates, chief executive of the Bioindustry Association said: “The proposed changes to NICE’s methods published today send an important signal to the innovative biotech sector that the UK is serious about ensuring access to new medicines.

“We are very encouraged by the focus on removing significant barriers to access, which puts the UK on a new footing, setting the benchmark for health technology appraisals – particularly around modifiers, uncertainty and discounting. It will help ensure both that industry can continue to deliver innovative medicines and that patients can access them.”

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Ring 20: Could the rare disease get left behind by next-generation gene sequencing?

Ring Chromosome 20 Syndrome, or (R)20, is an ultra-rare form of epilepsy with a devastating impact – yet despite huge leaps forward in gene sequencing in recent years, diagnoses are going down instead of up. We spoke to Allison Watson, co-founder of Ring 20 Research and Support, about raising awareness, building the evidence base, and the importance of helping people through a pandemic despite limited funding.

Allison’s son David was just six when he started displaying the symptoms of (R)20, a genetic condition that can cause multiple, uncontrollable seizures, declines in cognition and mobility, and terrifying hallucinations.

As with many cases of (R)20, often called ring 20, David’s seizures appeared to come out of the blue.

“Unlike with many similar conditions, a child will develop normally until the seizures start to kick in,” said Allison.

“The child will often go backwards and lose abilities that they previously had. They may lose the ability to process properly or to speak. They might lose mobility and need a wheelchair. Others need help feeding.”

Ring 20 is a chromosome anomaly. Instead of being a pair that looks like two sticks, one or both arms of the 20th chromosome are joined at the ends, making them look like a ring under the microscope.

“A lack of awareness of the condition, which is known to affect at least 150 people worldwide, contributes to a diagnostic delay, said Allison, adding that children often experienced nocturnal, hallucinogenic seizures that healthcare professionals were simply not familiar with.”

The resulting seizures vary – in length, type, and severity – from person to person, but even mild forms of the disease have a huge impact on quality of life.

Typically, people have impaired awareness seizures that can last anywhere between 20 and 40 minutes. For some, this can go on for days, leaving them in hospital or even in an induced coma.

“My son, who is now 23, will have four to six non-convulsive events every day – that’s just normal.

“It’s like the lights are on but no one is home, so you have to be really careful. They could be doing something like cooking or having a bath. It really impedes their independence,” said Allison.

Non-existent treatments and diagnostic challenges

Despite the huge unmet need, ring 20 diagnosis is slow, and treatments are practically non-existent.

“Ring 20 doesn’t respond to any treatments: nothing seems to work. There are no clinical practice guidelines, meaning doctors treat on a case-by-case basis. They are effectively working blind,” said Allison, who co-founded the charity in 2014.

“Families just have to learn to live with these regular seizures and the associated comorbidities.”

A lack of awareness of the condition, which is known to affect at least 150 people worldwide, contributes to a diagnostic delay, said Allison, adding that children often experienced nocturnal, hallucinogenic seizures that healthcare professionals were simply not familiar with.

“A child may appear to awake from sleep. They may shake or shout out and can have a stiffness in their bodies or their arms. They may have a frightened expression on their face, and some describe horrific events. They see sharks swimming around their head, or fire in the room, or big black holes jumping up in front of them.

“This is often misdiagnosed and disregarded as night terrors, so this obviously denies diagnosis.”

Another, apparently contradictory, point is that the number of ring 20 diagnoses have actually declined with advances in genome sequencing, which cannot detect the presence of ring chromosomes.

Allison explained: “Human genome sequencing, exome sequencing, and even CGH array all look for additions, duplications, or something missing from the DNA. But in the majority of ring 20 cases, there is no misspelling in the chromosome.

“The way to diagnose it is to go back to the old-fashioned carrier type, to physically look at the cells under a microscope to see the rings.”

Additionally, doctors looking for a chromosome abnormality would typically send 30 cells for analysis. But the misshaped chromosomes that characterise ring 20 are only present in a certain proportion of the person’s cells.

Said Allison: “They need to be sending about 100 cells for analysis, otherwise they could miss the ring.

“We suspect that this particular disease is very underdiagnosed in people with genetic epilepsies or an undiagnosed cause for epilepsy, and we also suspect that people that do have a diagnosis may be potentially misdiagnosed.”

Raising awareness, offering support

That’s why Allison is so keen to build the evidence base and raise awareness of the condition.

As co-chair for EpiCARE, the European Reference Network for rare and complex epilepsies, she is working on projects ranging from a patient pathway map to e-learning modules for healthcare professionals.

And members of Ring 20 Research and Support have raised enough money to embark on a two-year natural history and biomarker study, as well as establish a patient registry.

“This is a fundamental building block to future research opportunities so we’re very proud of our families for getting us to this point,” she said, adding that the registry “would have been up and running by now if it wasn’t for COVID”.

The pandemic caused both a surge in demand and a drop-in financial support – a problem that has been seen across the patient support sector.

But with it being more important than ever to ensure people with ring 20 and their families get the support they need, so COVID or no-COVID, Allison and her team have no intention of scaling back their plans. In fact, they have even extended their offering to include online peer networking.

“Because our families are so disparately located, some may never get to meet another family with ring 20 at all. So, we have been having fortnightly Zoom calls. We’re connecting families from the US and Australia, the UK and Europe, even South Africa,” said Allison.

“We’re based in the UK, but we support families worldwide. We’re the only organization doing this,” said Allison.


Cambridge Rare Disease Network Exploring Rare Diseases is produced in partnership with Cambridge Rare Disease Network (CRDN). CRDN is building a vibrant network of patients and stakeholders to share knowledge and foster innovation that leads to better diagnosis, treatment and support for those living with a rare disease

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Rare diseases, repurposing and the role of AI

In the age of artificial intelligence, no trial data should be going to waste. Findacure’s Rick Thompson looks at how these technologies could bring us closer to treatments for underserved rare diseases.

The repurposing of drugs is becoming more common, especially in the field of rare diseases.  In the past, repurposing has mostly been driven by academics looking for new possibilities in generics. Now, as part of lifecycle management, pharmaceutical companies are looking more closely at drugs they have on their shelves. These might be licensed drugs that could hold potential for a patent extension, or drugs which failed efficacy trials for an intended indication.

In the quest to repurpose a drug for a rare condition, there is a need to look at any and all available data. The wealth of published scientific literature forms one crucial source of data, with the ever-expanding pool of ‘omic data forming another.

A third pool of clinical evidence is formed by trial data, which will probably only be considered through the published literature. By definition, however, trial master files represent a much richer and more detailed source of data on a drug and how it performs. Published literature tends to catalogue successful clinical trials, but value can also lie in a trial that did not lead to a positive and viable outcome: the data it produced could still provide evidence for repurposing. For instance, provided a drug has not failed a trial on safety, the side effects it caused in one population could constitute on-target effects in another.

With large datasets crucial to gaining an understanding of rare diseases and opening the door to drug development, digital technology is proving transformative. It enables careful collation and organisation of information, but the innovations of artificial intelligence (AI) are now taking things further, facilitating the effective analysis and interrogation of big data to create new treatment hypotheses.

“Patient associations are working to develop registries (some using wearable technologies or apps) and natural history studies, which means that ever-greater volumes of data are being produced”

These techniques make the production of and access to high-quality data on rare diseases the gateway to treatment identification, and so are proving more crucial than ever for organisations in pharma.

Digitised, rigorously controlled data lends itself to techniques of processing and analysis which characterise both drug discovery and drug repurposing.

Raw text can be analysed by Natural Language Processing (NLP) techniques which form connections between studies that could otherwise take thousands of hours of human time to identify.

When combined with analyses of ‘omic approaches, and an appropriate level of disease-specific knowledge from patient groups, you can create a powerful resource for the identification of new treatment hypotheses for rare diseases – and an opportunity to address severe unmet needs.

Findacure is a charity that works directly with rare disease patient groups to help them grow and professionalise. Over the last five years we have focused on the power of drug repurposing for rare genetic diseases. It is estimated that, worldwide, just 400 treatments are licensed for 7000 known rare conditions, which tend to be determined by a very specific genetic factor.

As a consequence, most patients are being left with no hope of a treatment in their lifetime. Luckily, patient associations are working to fill the void by uniting patients and driving research forward for their conditions. Many are working to develop registries (some using wearable technologies or apps) and natural history studies, which means that ever-greater volumes of data are being produced.

This drive to generate data on and interest in their condition – along with the collated knowledge of their community’s lived experience of rare disease – can prove transformative to the treatment landscape. We are now seeing patient associations involved in several collaborative efforts that are identifying drugs which, as candidates for repurposing, stand to deliver treatments to rare disease patients more quickly and cheaply.

In 2020, the pharmaceutical industry has not by any means proved immune to the disruption caused by COVID-19. But, as in other industries, the pandemic has accelerated the process of digital transformation that was already underway.

A recent survey of more than 200 life sciences professionals, conducted on behalf of digital archiving specialists Arkivum, found 70% of respondents saying that COVID-19 has triggered a change in the way clinical trials will be conducted. There can be no doubt that digital technology will play a key role in that change. The survey reports that over 90% of sponsors and CROs have already adopted an eClinical application to improve study execution and data collection in live trials.

When a trial is completed, the valuable and extensive data it has produced must be archived – an exercise crucial both to regulatory compliance and to any future efforts at repurposing. 70% of sponsors reported that they use a digital archive rather than the traditional paper-based option, and 45% of respondents cited the role that clinical trial data plays in finding new indications and formulations. Yet at the same time, 38% of sponsor organisations described their ability to access archived clinical data and records as ‘extremely or very inadequate’.

This percentage rose to 65% amongst QA, compliance, legal and regulatory professionals. Moreover, just 31% of life sciences organisations seem to run a digital archive of sufficient sophistication to ensure that data can be managed in accordance with the FAIR data principles.

These were established to further scientific study through keeping data Findable, Accessible, Interoperable and Re-usable – all key attributes when it comes to exploring the new potential of an existing drug.

In the search to repurpose drugs, readier, more reliable access to archived trial data – including trials that produced negative results – can clearly prove highly beneficial.

If data has been well stewarded before and after it reaches the archive, and if its integrity has been maintained through careful curation, it facilitates the application of AI techniques. Natural language processing can be used in conjunction with, say, analysis of ‘omic-level data and patient group insights in order to work through the problems and side effects encountered in the full spectrum of trials. This can open the way to repurposing for different populations, and to new approaches to the design of clinical trials.

The success of these endeavours will also be favoured by the availability of comprehensive rare disease registries which collate patient-level data on disease natural history while also bringing together a pool of patients who could participate in trials.

Meanwhile at the pre-competitive stage of drug development, researchers are adopting a more open, collaborative approach to data. Now is the time to enable further collaboration by increasing access to historical data and releasing its full value. Success in finding treatments for rare disease is above all the product of collaboration, as technological innovation complements and amplifies a compassionate, patient-centred approach.

In all this, it is worth remembering that the people who participate in clinical trials – especially in the field of rare disease, where recruitment of patients is a particular challenge – would appreciate knowing that their participation will have a lasting value, whatever the outcome of the trial.

Trial participants take on a burden by putting in time, effort, hope and commitment. They also put themselves at some degree of risk whenever they take an experimental drug. In the field of rare diseases, trial participants are hoping to help the next generation of patients even more than themselves.It is crucial to maximise the potential value of data they are helping the professionals to collect.

With repurposing on the table, and improved access to all trial data, we can better unlock this potential.

About the authors

Dr Rick Thompson is CEO of Findacure, a UK charity dedicated to building the rare disease community to drive research and develop treatments.

Tom Lynam is head of Marketing at Arkivum, specialists in digital preservation of valuable data in life sciences and global scientific institutions.



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Flying the flag for research in Aarskog syndrome

Delayed diagnosis, lack of awareness, and a limited evidence base – Aarskog syndrome faces all the challenges of rare diseases everywhere. But a new study hopes to kick start a revolution in understanding.

For five years, Michelle Erskine faced a succession of closed doors and disbelief as she struggled to convince someone that all was not well with her son.

Eventually, after undergoing five operations in as many years, he was seen by a Consultant Ophthalmologist with knowledge of the condition and was placed on the road to an Aarskog syndrome diagnosis.

“When I saw it in black and white, I just burst into tears,” says Michelle, founder of the Aarskog Foundation, which recently marked Aarskog Awareness Week from 29 September to 4 October.

“Up until then, I was unable to convince anyone that something was wrong. We kept going to the nurse and the GP, but we were never referred to a paediatrician. No one would listen.”

The rare, X-linked genetic condition is characterised by short stature and facial, limb and genital abnormalities and was first described in 1970.

Michelle, who had recognised similarities between her son and two of her brothers, who had never been diagnosed, set up the Facebook page that eventually evolved into the foundation 12 years ago.

“I wanted to start a conversation and give people a space where they would be listened to. But from that, I wanted to formalise things – if all we do is talk as a group then nothing will ever get done”

Together with two fellow ‘Aarskog mums’ who had started social media pages around the same time, she had soon made contact with around 100 people from four countries around the world.

“I just wanted to start a conversation and give people a space where they would be listened to, so that no other mother would feel alone again. We were talking about the characteristics of the condition, advising people on how to speak to a GP, when to get a referral, etc.,” says Michelle.

“But from that, I wanted to formalise things – if all we do is talk as a group then nothing will ever get done. As my mum used to say: ‘if you do what you’ve always done, you’ll get what you’ve always got’.”

Variable impact

The Aarskog Foundation was established in 2017 and was given charitable status the following year. The objective, Michelle says, was to ensure families like hers received the support they needed.

“I wanted to change the dynamic, I wanted to raise awareness of the condition, and I wanted to help people to get a diagnosis,” says Michelle, who has published a six-step care plan pathway, which includes when to ask for a referral to a geneticist, on the foundation’s website.

As with many rare diseases, part of the problem families come up against when seeking care is a lack of solid evidence.

It is thought that around one in 25,000 people live with the condition, but the characteristics vary from person to person.

Most experience some form of cognitive difficulty, and some develop psychosocial problems related to short stature and feelings of social isolation.

The physical impact of Aarskog is extremely wide ranging.  Michelle’s son, who is now 22, needed operations for undescended testicles and a bilateral hernia before his fifth birthday, for example.

“The challenge we have with Aarskog syndrome is that the medical literature hasn’t extensively addressed the natural history and the spectrum of symptoms,” she says. “Although the advancements in sequencing technologies have enabled the genetic confirmation of this disease, an effort to understand the genetic basis of this multitude of symptoms is still due.”

For instance, all our children are on the autistic spectrum in one form or another. Still, there is a considerable lack of literature discussing the variability and etiopathogenesis of the autism spectrum disorder in Aarskog syndrome.”

Because Aarskog is an X-linked genetic condition affecting predominantly males, women have traditionally been considered asymptomatic carriers. However, Michelle believes that around 80% of the mothers she speaks to have an inflammatory disease such as rheumatoid arthritis or ankylosing spondylitis that should be evaluated for any association with this syndrome.

“Women have traditionally been considered asymptomatic carriers – but Michelle believes that 80% of the mothers she speaks to have an inflammatory disease such that should be evaluated for any association with Aarskog syndrome”

We are not aware of so many aspects of this disease because they have not been researched adequately,” she says.

Because this disease is so rare and there is no cure yet, it is not seen as important by researchers and physicians. This is what I want to change. I want people to have a system that they can rely on and be supportive”

Natural history study

To this end, Michelle’s foundation has just started working with two medical geneticists to identify and delineate the syndrome’s novel characteristics. This human history study project will use data from the foundation’s patient registry.

This study will primarily use the data to understand the natural history of the disease phenotype so that we can help the patients and families with better care of their ailments.

At the moment, there is information about this disease, but it’s neither concise nor comprehensive in nature.”

The human history study, which is being funded by the foundation and its supporters, will feed into gene reviews, an international point-of-source for inherited disorders. The team hopes that this study’s scope will also shed light on the gene’s impact on the women who carry it in addition to an elaborative genotype-phenotype correlation.

The two research projects, Michelle says, will start to build the evidence base.

This condition causes so much pain for families. I hope the research encourages clinicians to look into this further so that they can better inform people about the condition and put people on better management pathways,” she concludes.

To contribute to the cost of the studies, click here

Cambridge Rare Disease Network Exploring Rare Diseases is produced in partnership with Cambridge Rare Disease Network (CRDN). CRDN is building a vibrant network of patients and stakeholders to share knowledge and foster innovation that leads to better diagnosis, treatment and support for those living with a rare disease

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BioMarin files achondroplasia drug after rejection for haemophilia therapy

US biotech BioMarin has hit back with a filing for a rare disease drug, after suffering what was described by analysts as a “major setback” when the FDA rejected its gene therapy for haemophilia A.

California-based BioMarin said the US filing for vosoritide in achondroplasia could lead to the first treatment for children with achondroplasia, the most common form of disproportionate short stature in humans.

This follows a European filing last week for the once daily injection of the analogue of C-type natriuretic peptide, although the company gave no details about a possible FDA decision date.

But the achondroplasia filing came the day after an unexpected FDA rejection for BioMarin’s haemophilia A gene therapy Roctavian (valoctocogene roxaparvovec), which analysts estimate will delay approval by around two years.

BioMarin previously agreed with the FDA on a data package necessary to support approval, but the company said the regulator has introduced a new recommendation for two years of safety and efficacy data.

This data could be generated by the ongoing phase 3 GENEr8-1 trial which uses annualised bleeding rate as a primary endpoint.

The company said the new recommendation was not raised at any time during development or review.

There was no FDA inspection at its manufacturing facility for Roctavian, suggesting the regulator knew a rejection in a Complete Response Letter was due.

However a team of analysts from Jefferies said that EU regulators had given the manufacturing facility a clean bill of health should the product get approval on the other side of the Atlantic.

Describing the rejection as a “major regulatory setback” a team of analysts from Jefferies led by Eun Yang said a worst-case scenario where both drugs are rejected could reduce sales by 25% compared with previous estimates.

BioMarin already markets seven rare disease drugs and has seen its PARP inhibitor Talzenna (talazoparib), developed in partnership with Pfizer’s Medivation unit, get approval in the US and Europe.

It also has three other gene therapies in its pipeline for phenylketonuria, hereditary angioedema, and hypertrophic cardiomyopathy.


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Healx uses AI to find drugs for Angelman Syndrome

The UK-based AI technology company Healx has begun a partnership with the Foundation for Angelman Syndrome Therapeutics (FAST), focusing on developing new therapies for the rare neurogenetic disorder.

The latest project will focus on quickly identifying and progressing novel treatments for Angelman syndrome, which is caused by several genetic mutations.

But the most significant is loss of function in a protein-making gene called UBE3A, which leads to complications in the nervous system and severe issues with movement, balance and speech.

There are no approved treatments – something that the Cambridge company aims to change by using patient insights during the development process.

Healx said that by working with FAST, it aims to create a “collaborative model” of drug discovery.

Dr Bruce Bloom, chief collaboration officer at Healx, said: “(Patients) are the ones driving forward research efforts to find new treatments, and have a wealth of experience and insight about what it’s actually like to live with these conditions.

“By integrating their expertise early on, and connecting to their well-developed scientific and clinical network, we have a better chance of finding critical new therapies.

“We’re really excited about working with FAST and hope to move our AI predictions towards preclinical validation in the second half of the year.”

Healx already has a collaboration with the UK’s muscular dystrophy research, support and advocacy charity Muscular Dystrophy UK.

The project will focus initially on a condition called facioscapulohumeral muscular dystrophy (FSHD), which causes muscle-weakening in the face, shoulder blades and upper arms.

In April Healx also began working with the Children’s Tumor Foundation to develop new therapies for neurofibromatosis, another rare genetic disorder affecting one in 3,000 people worldwide.

Earlier this year the company started using its technology to uncover combinations of drugs that could be used against the SARS-CoV-2 coronavirus.

The company hoped to use data to find out why mortality is higher in patients with comorbidities and problems with respiratory and cardiac systems.

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NS Pharma takes on Sarepta as FDA approves DMD drug

The FDA has approved a new therapy for the rare muscle wasting disease Duchenne muscular dystrophy (DMD) as Japan’s NS Pharma takes on Sarepta and its controversially approved rival.

NS Pharma’s Viltepso (viltolarsen) has been approved in patients who have confirmed mutation of the DMD gene that is amenable to exon 53 skipping.

The DMD gene is made up of 79 exons, and mutations in that code can result in a deficiency in dystrophin which is responsible for the muscle wasting in DMD.

Exon-skipping drugs are used to patch the mutations and allow the gene to produce partially functional dystrophin.

Viltepso can be used to treat around 8% of DMD patients and previously approved DMD drugs has not been shown to change the course of the disease.

However what it does do is help produce the dystrophin that patients with the disease are lacking.

It’s bad form to compare performance of drugs in separate clinical trials, but results suggest that Viltepso helps patients produce more dystrophin than Sarepta’s rival Vyondys 53 (golodirsen).

The FDA controversially approved Vyondys 52 late last year after a previous rejection and an appeal from Sarepta.

Viltepso was evaluated in two clinical studies with a total of 32 patients, all of whom were male and had genetically confirmed DMD.

The increase in dystrophin production was established in one of those two studies, a study that included 16 DMD patients, with 8 patients receiving Viltepso at the recommended dose. In the study, dystrophin levels increased, on average, from 0.6% of normal at baseline to 5.9% of normal at week 25.

The FDA deemed that this increase in dystrophin production is “reasonable likely” to predict a clinical benefit –something that is difficult to measure in such a small study.

As part of the accelerated approval process, the FDA requires NS Pharma to conduct a trial to confirm clinical benefit.

This ongoing study will assess whether Viltepso improves the time to stand for DMD patients with the confirmed mutation.

If the trial fails to verify clinical benefit, the FDA may begin proceedings to withdraw approval.

The most common side-effects in the two trials were upper respiratory tract infection, injection site reaction, cough and fever.

There have been no signs of liver toxicity in the 80 patients treated so far, but the FDA is warning doctors to monitor renal function as this issue has been observed in patients taking antisense oligonucleotides.



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How does HTA for orphan drugs differ across europe?

New research looks at the factors that speed up and slow down HTA appraisals for rare disease medicines across Europe.

Rare diseases drugs have always faced challenges when it comes to HTA approvals, even as governments bring in more regulatory policies that make their path through assessment easier.

Several factors make it difficult for HTA bodies often to assess orphan drugs, including a lack of robust trial data due to difficulties in finding patients, the absence of randomised controlled trials, the use of surrogate endpoints, and the lack of active drug comparators.

A new analysis from consulting firm CRA has honed in on the different challenges faced in four EU markets – England, France, Germany and Scotland – and looked at how manufacturers can increase the chances of a successful appraisal.

The research analysed more than 70 EMA-approved rare disease therapies and compared reimbursement recommendations from the regulatory bodies in each country, to see how HTA decisions potentially prolonged time to reimbursement.

The results show that HTAs for orphan drugs can vary widely across Europe, causing inconsistencies in evidence requirements and recommendations.

Rates of approval

The study reviewed all 80 European Medicines Agency (EMA) authorised drugs receiving an orphan designation between 1 January 2013 and 31 December 2019, analysing their HTA outcomes and time to reimbursement across France, Germany, England and Scotland.

A comparative analysis was then conducted on the 71 approved drugs that achieved a negotiated price in at least one of the four markets.

Germany had the highest approval rate of orphan drugs at 98% – however most of these recommendations (73%) were awarded a ‘non-quantifiable benefit’ rating, the automatic rating for an orphan drug, which shows the regulator did not see any benefit compared to comparator products (see graph 1). The authors also note that orphan drug trials with higher p values and surrogate endpoints are often accepted for assessment in the country.

A more favourable outcome from the German regulator took on average 1.4 times longer to achieve a final negotiated price (708 versus 510 days).

graph 1

Graph 1: Assessment of the HTA outcome in France, Germany, England and Scotland of all orphan drugs that obtained an EMA approval between 2013-2019. N above each bar equals the number of drugs reviewed by the respective HTA body. Source: CRA Analysis

France and England had comparable approval rates (92% and 91%, respectively); however, France reviewed almost twice the number of orphan drugs over the period of analysis (67 versus 35). Only 19% of the orphan drugs in France were awarded an Amelioration du Service Médical Rendu (ASMR) rating of V, which indicates no improvement in medical benefit. Drugs with an ASMR IV-V rating were reimbursed in 427 days, compared to 585 days for products with ASMR I-III (see Graph 2).

Graph 2

Graph 2: Comparison of the time to reimbursement (days) for EMA orphan drugs approved from 2013- 2019. Orphan drugs were reimbursed in at least one of the selected markets (N = 70). N within each bar equals the number of drugs with each outcome reviewed by the respective HTA body. Source: CRA Analysis

In England, two key mechanisms were often used to achieve approval: label restrictions or a patient access scheme (PAS).

Over one third (37%) of orphan drugs appraised by NICE only achieved approval in a positioning or population that was restricted versus the full regulatory approved label. Companies that accepted such restrictions saw faster approval time compared to no drugs with restrictions (407 versus 505 days).

Meanwhile, although introducing a PAS improved the chance of approval, the analysis suggests that it actually delays the overall appraisal time (523 versus 311 days).

Scotland had the highest rate of non-approval for orphan drugs. Thirty-three percent of drugs reviewed were not accepted, despite specific modifiers in place for rare disease products, including the incorporation of the patient voice through the country’s Patient and Clinician Engagement (PACE) meetings – which were included in 74% of orphan drug submissions between 2013-2019.

Improving HTA outcomes

The authors conclude that while the various concessions and modifiers introduced by different governments have a positive impact on minimising rejections and accelerating approval times, there are still challenges in capturing the full value of orphan drugs within the HTA process.

“Achieving more favourable outcome ratings, avoiding restrictions, or addressing uncertainty with a PAS all lead to prolonged appraisal times,” the  authors say. “Manufacturers are therefore still required to consider carefully their HTA launch strategy and complement this with additional evidence generation and engagement from a wider stakeholder group.”

The authors outline several approaches companies can take to improve the chances of success in orphan drug approvals and overcome the challenge of having limited data and evidence available.

One approach is to agree methods for ongoing real world data collection post-launch with HTA bodies.

They add that “creative” solutions to real world evidence collection could help, such as developing apps for patients and HCPs.

Meanwhile, it is also important to strive for wider engagement with the rare disease community and other stakeholders.

Listening to views from patients and HCPs can help with processes like Scotland’s PACE meetings – but more indirect forms of stakeholder engagement may also improve HTA outcomes, as the value-added services provided to these stakeholders can be leveraged during negotiations.

“For example, Galafold, an enzyme replacement therapy for Fabry’s disease, is primarily differentiated from existing treatments by providing a reduction in administrative burden,” the authors say. “Despite this, Galafold was able to achieve an ASMR IV in France, recommendation by NICE, and was accepted for restricted use in Scotland.”

They note that the perception of Galafold’s value may have been improved by the additional value-added services the manufacturer, Amicus Therapeutics, offered to a wider stakeholder group

For example, Amicus reimbursed amenability tests for patients with unknown mutations that could be referenced against Galafold’s amenability table via a physician support website. This service was accepted in the NICE evaluation as something which avoided additional resource implications for the NHS.

For more information contact the report’s authors:

Steven Kelly – [email protected]

Ioanna Stefani – [email protected]

Charlotte Poon – [email protected]

Nimisha RaJ – [email protected]

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Biogen plans trial of Spinraza in patients not responding to SMA gene therapy

Biogen is planning to trial its Spinraza spinal muscular atrophy (SMA) drug in patients who have not responded properly to Novartis’ gene therapy Zolgensma, combining the two ultra-expensive therapies to treat the rare muscle-wasting disease.

In the US, a single shot of Zolgensma (onasemnogene abeparvovec) costs $2.1 million, while Spinraza (nusinersen) costs $750,000 in its first year.

Biogen said it aims to begin a phase IV study as in a long-term follow-up study of Novartis’ drug it has been reported that some patients have been subsequently treated with Spinraza.

The phase IV RESPOND study aims to test efficacy and safety of Spinraza with a suboptimal clinical response to Zolgensma.

So far four out of 10 patients in a long-term study of Zolgensma have been subsequently treated with Spinraza, Biogen said.

Based on the planned study design, RESPOND will be a two-year, open-label study to evaluate the efficacy and safety of Spinraza in SMA patients previously treated with Zolgensma to further inform treatment decisions.

Efficacy will be assessed by change from baseline on motor function measures and additional clinical outcomes such as swallowing and caregiver burden.

Neurofilament levels, an exploratory endpoint, will also be evaluated as a marker of biological disease activity.

The primary study group aims to include 40 infants aged nine months or younger at the time of the first dose of Spinraza, who have two copies of SMN and are likely to develop type 1 disease and received Zolgensma at six months old or younger.

A second study group will include 20 children and will generate data in patients with a broader age range, up to three years old at the time of the first Spinraza dose.

After a screening period, participants will receive the approved 12 mg dose of Spinraza, which is four loading doses followed by maintenance doses every four months, over the two-year study period.

If approved by regulators the company aims to begin enroling patients in the first quarter of next year.

While Zolgensma is a gene therapy that aims to correct the genetic defect that causes the disease, Spinraza works by increasing the amount of full-length SMS protein that is critical to maintaining motor neurons.

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Pandemic hits sales at Novartis after strong launch for SMA gene therapy

The COVID-19 pandemic has bit into sales at Novartis, the big Swiss pharma said in second quarter results, after orders fell back following a period of stockpiling earlier in the year.

Figures for the quarter showed reported sales fell by 4% to $11.3 billion compared with the corresponding period last year, although favourable currency fluctuations helped to soften the impact.

Net income was a reported $1.9 billion, down 11% compared with last year’s Q2.

The company said that COVID-19 negatively affected sales in April and May, mainly because of fewer patients starting courses of medicine and reducing visits to the doctor.

Novartis added that digital technology and new ways of working are helping to keep the company running smoothly and have reduced costs.

It has a digital clinical trial management system that has allowed trials to continue despite the disruption caused by the coronavirus outbreak.

The company said measures had “limited COVID-related impacts” to trial data filing timelines.

Results also showed a strong launch for its rare diseases gene therapy, Zolgensma, which is now approved for the muscle wasting disease spinal muscular atrophy (SMA) in the US and EU.

Zolgensma is a one-off shot that corrects the underlying genetic cause of the disease and is notable for being the world’s most expensive drug at $2.1 million.

Novartis’ AveXis unit only began launches of the drug in Europe this month, a few weeks after the drug hit the market in Japan.

But sales in the US are going well, where payers are clearly finding ways to deal with the drug’s price tag.

In Q2 Zolgensma generated revenues of $205 million, and for the half year they were $375 million.

Novartis’ psoriasis drug Cosentyx continues to gain traction with sales increasing by 10% to $944m in Q2, but sales of multiple sclerosis pill Gilenya fell in a competitive market, down by 11% to $738 million.

There is also a potential threat of generic competition to Gilenya, although Novartis said its forecasts assume that there will be no US generic approved this year.

The company said that guidance has “tightened” within previously announced ranges – net sales are expected to grow mid single digit, with core operating income expected to grow low double digit.


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Inozyme plans $75m IPO as it heads for clinic with rare bone diseases drug

US biotech Inozyme Pharma is the latest to jump on to the IPO bandwagon, setting terms for a $75 million stock market launch, as the firm gears up for clinical trials of its lead drug for rare bone diseases.

Based in Boston, Massachusetts, the company plans to raise $75 million by offering 5 million shares at a price range of $14 to $16.

This is at the midpoint of the proposed range, where Inozyme Pharma could command a fully diluted market value of $332 million.

Founded in 2015, Inozyme wants to list on the Nasdaq under the symbol INZY.

Boston, Massachusetts-based Inozyme’s lead candidate is INZ-701, a soluble, genetically engineered protein designed to correct a defect in the mineralisation pathway.

The company plans to file for approval to begin clinical trials in the US and Europe in the second half of this year, followed by phase 1/2 trials.

With INZ-701, the company is targeting a variety of mineralisation disorders linked mainly to mutations in the ENPP1 and ABCC6 genes.

The drug is designed to replace the lost enzymatic function of deficient ENPP1 by restoring normal balance in pyrophosphate.

It is designed to be delivered subcutaneously and to linger in the system, leading to steady concentrations in the blood over time and making dosing possible at infrequent intervals, possibly weekly.

The COVID-19 pandemic has seen biotech stocks becoming increasingly popular with investors, allowing unlisted biotechs to raise large sums with stock market launches.

Last month Royalty Pharma set Wall Street on fire with its oversubscribed $2.2 billion IPO, selling 77 million shares.

The IPO raised around $300 million more than expected and shares surged after the debut, surging 59% on the first day of trading to close at $44.50.

As its name suggests Royalty Pharma is the largest player in the niche area of pharmaceutical royalty agreements.

The company’s revenues all come from royalty payments resulting from rights it holds to experimental or marketed drugs, either acquired from other developers or resulting from funding contributions to development programmes.

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Novel Platforms in Ocular Drug Delivery workshop discussed at Ophthalmic Drugs

SMi reports: Dr. Thakur Raghu Raj Singh from Queen’s University Belfast will lead the post conference workshop on Wednesday 25th November 2020.

SMi presents the 4th Annual Ophthalmic Drugs Conference taking place on the 23rd -24th November 2020, in London. SMi are also pleased to announce that they will be hosting a half-day post-conference workshop, Wednesday 25th November 2020 at 08.30 – 12.30.

Those who register by the 30th September will save £100 with the early bird discount:

Workshop will be on ‘Novel Platforms in Ocular Drug Delivery’. Hosted by Dr. Thakur Raghu Raj Singh, Reader in Pharmaceutics, Queen’s University Belfast.

In this workshop, challenges associated with different delivery systems and routes of administration will be explored. The benefits and challenges in the design of long-acting (LA) drug delivery systems will be analysed. In this session there will be a use tangible examples of both ocular and non-ocular LA technologies that have been successfully launched in the market. Finally, it will focus on the design space of LA technologies for small molecules vs biologics and the applicability of devices in the delivery of LA formulations.

By attending delegates will learn current unmet medical needs in the treatment of ocular diseases. They will be able to discuss current LA products on the market by analysing both ocular and non-ocular technologies. Also discuss challenges in the design of a LA ocular drug delivery technology for small vs large molecules. Attendees will be able to learn the role of devices in the delivery of LA drug delivery systems and review novel LA technologies under development.

About the workshop leader

Dr Raj Thakur is a Reader in Pharmaceutics at the School of Pharmacy (SoP), QUB and is the Founder, CTO and Director of Re-Vana Therapeutics. His research interest is in the design and physicochemical characterisation of advanced long-acting biodegradable drug delivery systems including minimally invasive medical devices for localised drug delivery. He is the Chair for Ocular Drug Delivery (OcDD) Focus Group supported by the mission of Controlled Release Society (CRS). He has authored over 160 scientific publications, including 60 full papers, 10 book chapters, five textbooks, several invited talks in national and international conferences and patents.

Interested parties can learn more about the workshop and full agenda by visiting:

Ophthalmic Drugs Conference

23rd -24th November 2020


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About SMi Group:

Established since 1993, the SMi Group is a global event-production company that specializes in Business-to-Business Conferences, Workshops, Masterclasses and online Communities. We create and deliver events in the Defence, Security, Energy, Utilities, Finance and Pharmaceutical industries. We pride ourselves on having access to the world’s most forward-thinking opinion leaders and visionaries, allowing us to bring our communities together to Learn, Engage, Share and Network. More information can be found at

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