Aurinia’s Lupkynis for Lupus; FDA Fast Track Designation for Toripalimab; Wren Therapeutics’ Financing; Merck’s Covid-19 Vaccine Program End

Hot on the heels, Aurinia launches its drug in the Lupus market after GSK

Aurinia Pharmaceuticals has recently got the USFDA approval for its Lupkynis (voclosporin) in combination with a background immunosuppressive therapy regimen to treat adult patients with active Lupus nephritis (LN). Lupkynis is the first oral therapy to receive FDA nod for Lupus nephritis, a condition that causes inflammation of kidneys. It is one of the most common and serious complications of the autoimmune disease systemic lupus erythematosus (SLE). 

Lupus has been a challenging condition to treat for decades with only a limited number of therapeutic options. However, Aurinia is not the only player offering the cure. A month ago, GlaxoSmithKline earned the approval for its Benlysta, intravenous and subcutaneous option for Lupus, and became the first-ever therapy to get an approval for the indication. 

Although GSK has had an upper hand at the early launch of the drug, Aurinia has reported a significantly improved renal response rate of 40.8% versus 22.5% in the control arm while Benlysta’s difference with control was smaller (43% vs 32%). Furthermore, the company does not shy away from saying that its drug works rapidly and its oral RoA is another added benefit that makes it stand tall in the Lupus nephritis market. 

FDA Fast Track Designation to Toripalimab for Mucosal Melanoma

The USFDA granted Fast Track Designation to Junshi BiosciencesToripalimab for the first-line treatment of mucosal melanoma. Toripalimab is the first domestic anti-PD-1 monoclonal antibody to get commercial approval in China. 

The regulatory agency has also approved the Investigational New Drug (IND) application for a global Phase III trial of Toripalimab in combination with Axitinib versus Pembrolizumab for the first-line treatment of patients with advanced mucosal melanoma (Combination Clinical Trial). The trial investigated more than fifteen indications sponsored by over thirty pharmaceutical companies conducted globally, including in China and the United States. 

In 2018, Toripalimab had already obtained conditional approval from the National Medical Products Administration (the “NMPA”) for the second-line treatment of unresectable or metastatic melanoma. Further, it was included in the Guidelines of Chinese Society of Clinical Oncology (CSCO) for the Diagnosis and Treatment of Melanoma in 2019 and 2020 respectively. It also has received two supplemental New Drug Applications (NDAs) for the third-line treatment of recurrent/metastatic nasopharyngeal carcinoma and the second-line treatment of metastatic urothelial carcinoma were accepted by the NMPA in April and May 2020, respectively.

Wren Therapeutics Announces Financing of £12.4 Million 

Wren Therapeutics has announced the closing of a £12.4 million (c. $17.0 million) financing raising the total capital to approximately £33 million (c. $45 million). The financing was led by existing shareholder The Baupost Group, along with the participation from existing investors including LifeForce Capital and new investors including Schooner Capital and Industry Ventures.

The company plans to use the proceeds to accelerate two of its leading small-molecule programs towards the clinical development for the potential treatment of Alzheimer’s disease and various synucleinopathies including Parkinson’s disease

Merck Makes a Quick Exit in the COVID-19 Vaccine Development Fight 

The pharma goliath, Merck has decided to discontinue the development of its two experimental Covid-19 vaccines after the results from early trial gave some lacklustre results. Merck has taken a different approach from its rivals namely Pfizer, Moderna and Johnson & Johnson who were also in the domain developing vaccines against COVID-19

Merck had undertaken two programs, V590, which is based on the borrowed technology from Merck’s Ebola inoculation, whereas the second one, V591, is based on a measles vaccine used in Europe. However, both failed to cut the mustard this time and proved to be a blot in the company’s long history of successful vaccine development. 

Merck was a late-entrant in the development of the COVID-19 vaccine. The company had finished the recruitment of the first participants for early-stage safety studies at the time when its rivals were gearing up for presenting and demonstrating the efficacy of their candidates in late-stage trials. And the weak results took everyone by surprise. However, early or say quick fails are not as bad as the failure in the end-stage trials as they help the company to recover sooner from the grief and loss. 

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Biohaven’s Troriluzole Failure; Daiichi/ AZ’s Enhertu; Fujifilm & Manufacturing Spree; J&J’s Darzalex Faspro

Biohaven’s Troriluzole Dwindles Again In Alzheimer’s After Anxiety 

Biohaven Pharmaceuticals had put too much faith in its third-generation prodrug, Troriluzole. The company has tested the efficacy of the drug in more than one indication, including generalized anxiety disorder (GAD), obsessive-compulsive disorder, spinocerebellar ataxia and Alzheimer’s disease (AD). However, it seems the drug continues to disappoint the company one after another.

After the drug failed to produce better outcomes in anxiety, failed to meet primary outcomes in OCD, the company announced that their chemical entity that modulates glutamate, the most abundant excitatory neurotransmitter in the human body, has even flunked in Phase 2/3 clinical trial as a symptomatic treatment in mild-to-moderate Alzheimer’s disease (AD). 

Thus, the company has decided to wrap up the trials for AD. This is not something new in the Alzheimer’s disease market. Despite the availability of scientific evidence, extensive R&D, and investment of huge amounts, no new drug has managed to walk the carpets. Several have failed and abandoned with the plight and the cost of the disease seemingly growing with each year passing. 

A Sweet Year For Daiichi/ AZ As Enhertu Gets FDA Approval For Gastric Cancer

The U.S. Food and Drug Administration has given the nod to Daiichi Sankyo’s and AstraZeneca’s Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

Enhertu is an antibody-drug conjugate (ADC) that comprises a humanized anti-HER2 IgG1 monoclonal antibody. The approval is based on the positive results from the randomised Phase 2 trial conducted in Japan and South Korea. 

With the approval, Enhertu has become the first HER2-directed medicine approved in a decade for patients with HER2-positive metastatic gastric cancer. It is already approved for adults with unresectable or metastatic HER2-positive breast cancer who have had two or more previous anti-HER2-based treatments in the metastatic setting.  The company has future plans to pursue the trials for the drug across a broad range of HER2 targetable cancers.

Fujifilm Increases Legroom In Cell And Gene Therapy, Plans For New Manufacturing Facility  

Fujifilm and the Center for Advanced Biological Innovation and Manufacturing (CABIM) has secured USD 76 million in financing and also signed a lease for a 40,000 square-foot site in Watertown, Massachusetts at The Arsenal on the Charles, owned and operated by Alexandria Real Estate Equities. 

CABIM, the industry-academia research and development consortium, is a joint effort of Fujifilm, Harvard University, Massachusetts Institute of Technology, Cytiva (formerly part of GE Healthcare Life Sciences), and Alexandria Real Estate Equities, Inc. CABIM plans to help make new therapeutics, medicines, and technologies accessible to patients and strengthen Greater Boston’s position as the world’s life science capital. The plan is to build eight clean rooms, with a configuration to produce both cell and viral vector products within the physical space. 

Fujifilm is trying everything to build its position in the cell and gene therapy domain even stronger. With its CDMO arm, Fujifilm Diosynth Biotechnologies exploring more in-depth into the domain, and showing a shited interest in its viral vector capabilities for Covid-19 vaccines, will procure GMP2 contract process development and manufacturing services as part of its role in the new manufacturing and innovation centre.

J&J’s Darzalex Faspro Receives FDA’s Blessings For Amyloidosis

Janssen has announced that its Darzalex Faspro has received the USFDA approval for adults with newly diagnosed light chain amyloidosis. The drug was originally developed by Genmab in 2012 and was in-licensed to Janssen. 

Darzalex Faspro is a combination of daratumumab and hyaluronidase-fihj, a subcutaneous formulation of daratumumab. It is the only CD38-directed antibody that has got approval for subcutaneous injection for multiple myeloma, and now it has been given the nod for AL amyloidosis. The drug is approved in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) and is the first and only FDA-approved therapy for patients with this indication. 

AL amyloidosis affects over 4000 people each year in the US, and about 30% of patients with AL amyloidosis die in the first year after diagnosis. Today’s approval is nothing less than a breakthrough in the AL amyloidosis market. 

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Could Lilly’s donanemab readout in Alzheimer’s boost Biogen’s prospects?

When Eli Lilly reported results for donanemab in Alzheimer’s disease earlier this week it was hailed as a rare win for the amyloid hypothesis, although there’s no shortage of candidates that have failed despite positive mid-stage trial results.

Some analysts have intimated that given the small size of the study at just over 270 patients, rival amyloid drug developers Biogen and Eisai could claim the biggest benefit from the data in positive sentiment ahead of an FDA decision later this year.

Goldman Sachs analyst Terence Flynn said the result was a “positive surprise” after Lilly revealed top-line data from the TRAILBLAZER-ALZ study showing that donanemab slowed cognitive decline by a third in people with early Alzheimer’s and completely resolved the amyloid beta plaques that are a hallmark of the disease.

Flynn also said the data was an “incremental positive” for Biogen, whose Eisai-partnered aducanumab is already filed for approval and awaiting an FDA decision by 7 March, as it lends further weight to the amyloid beta hypothesis of Alzheimer’s.

Biogen is nearest to market with aducanumab but a positive verdict from the US regulator is far from assured. In November, an FDA advisory committee voted ten to one against approval, saying the clinical data backing the drug was inconclusive, but that came on the back of a positive assessment by the FDA’s own reviewer.

Wolfe analyst Tim Anderson said in a research note issued ahead of the donanemab readout that the FDA could be influenced by the donanemab data and – if positive – that would raise the chances of a greenlight for aducanumab.

There’s an alternative view however that donanemab’s data might actually harm aducanumab’s prospects. Analysts at Jefferies told Barron’s this week that the FDA may have been minded to approve Biogen and Eisai’s drug because there were no other late-stage candidates in play, but Lilly’s drug could change that perception.

Donanemab is unlike most other amyloid-targeting drugs – including aducanumab – because it targets a pyroglutamated form of amyloid beta called N3pG that is found only in amyloid plaques and according to some research can stimulate misfolding of proteins.

Lilly’s hypothesis – as yet unproven – is that clearing those plaques has a direct association with cognitive benefits.

Lilly says TRAILBLAZER-ALZ met its primary endpoint, slowing decline on the Integrated Alzheimer’s Disease Rating Scale in the donanemab group by 32% compared to placebo, with trends towards improvement on secondary endpoints that didn’t hit statistical significance.

On safety, around 27% of the treatment arm showed ARIA-E – an inflammatory reactions also seen with other amyloid-targeting antibodies – but there’s little other data available yet.

Lilly started a 500-patient phase 2 trial called TRAILBLAZER-ALZ-2 last June that it suggests could serve as a confirmatory pivotal study and potentially support regulatory filings – dramatically shortening the development timeline for the drug. That’s due to read out in next year or later.

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How Care Coordination Technology Addresses Social Isolation in Seniors

How Care Coordination Technology Addresses Social Isolation in Seniors
Jenifer Leaf Jaeger, MD, MPH, Senior Medical Director, HealthEC

Senior isolation is a health risk that affects at least a quarter of seniors over 65. It has become recognized over the past decade as a risk factor for poor aging outcomes including cognitive decline, depression, anxiety, Alzheimer’s disease, obesity, hypertension, heart disease, impaired immune function, and even death.

Physical limitations, lack of transportation, and inadequate health literacy, among other social determinants of health (SDOH), further impair access to medical and mental health treatment and preventive care for older adults. These factors combine to increase the impact of chronic comorbidities and acute issues in our nation’s senior population.

COVID-19 exacerbates the negative impacts of social isolation. The consequent need for social distancing and reduced use of the healthcare system due to the risk of potential SARS-CoV-2 exposure are both important factors for seniors. Without timely medical attention, a minor illness or injury quickly deteriorates into a life-threatening situation. And without case management, chronic medical conditions worsen. 

Among Medicare beneficiaries alone, social isolation is the source of $6.7 billion in additional healthcare costs annually. Preventing and addressing loneliness and social isolation are critically important goals for healthcare systems, communities, and national policy.

Organizations across the healthcare spectrum are taking a more holistic view of patients and the approaches used to connect the most vulnerable populations to the healthcare and community resources they need. To support that effort, technology is now available to facilitate analysis of the socioeconomic and environmental circumstances that adversely affect patient health and mitigate the negative impacts of social isolation. 

Addressing Chronic Health Issues and SDOH 

When we think about addressing chronic health issues and SDOH in older adults, it is usually after the fact, not focused on prevention. By the time a person has reached 65 years of age, they may already be suffering from the long-term effects of chronic diseases such as diabetes, hypertension or heart disease. Access points to healthcare for older adults are often in the setting of post-acute care with limited attention to SDOH. The focus is almost wholly limited to the treatment and management of complications versus preventive measures.  

Preventive outreach for older adults begins by focusing on health disparities and targeting patients at the highest risk. Attention must shift to care quality, utilization, and health outcomes through better care coordination and stronger data analytics. Population health management technology is the vehicle to drive this change. 

Bimodal Outreach: Prevention and Follow-Up Interventions

Preventive care includes the identification of high-risk individuals. Once identified, essential steps of contact, outreach, assessment, determination, referral, and follow-up must occur. Actions are performed seamlessly within an organization’s workflows, with automated interventions and triggered alerts. And to establish a true community health record, available healthcare and community resources must be integrated to support these actions. 

Social Support and Outreach through Technology 

Though older adults are moving toward more digitally connected lives, many still face unique barriers to using and adopting new technologies. So how can we use technology to address the issues?

Provide education and training to improve health literacy and access, knowledge of care resources, and access points. Many hospitals and health systems offer day programs that teach seniors how to use a smartphone or tablet to access information and engage in preventive services. For example, connecting home monitoring devices such as digital blood pressure reading helps to keep people out of the ED. 

Use population health and data analytics to identify high-risk patients. Determining which patients are at higher risk requires stratification at specific levels. According to the Centers for Disease Control and Prevention, COVID-19 hospitalizations rise with age, from approximately 12 per 100,000 people among those 65 to 74 years old, to 17 per 100,000 for those over 85. And those who recover often have difficulty returning to the same level of physical and mental ability. Predictive analytics tools can target various risk factors including:

– Recent ED visits or hospitalizations

– Presence of multiple chronic conditions

– Depression 

– Food insecurity, housing instability, lack of transportation, and other SDOH 

– Frailty indices such as fall risk

With the capability to identify the top 10% or the top 1% of patients at highest risk, care management becomes more efficient and effective using integrated care coordination platforms to assist staff in conducting outreach and assessments. Efforts to support care coordination workflows are essential, especially with staffing cutbacks, COVID restrictions, and related factors. 

Optimal Use of Care Coordination Tools

Training and education of the healthcare workforce is necessary to maximize the utility of care coordination tools. Users must understand all the capabilities and how to make the most of them. Care coordination technology simplifies workflows, allowing care managers to: 

– Risk-stratify patient populations, identify gaps in care, and develop customized care coordination strategies by taking a holistic view of patient care. 

– Target high-cost, high-risk patients for intervention and ensure that each patient receives the right level of care, at the right time and in the right setting.

– Emphasize prevention, patient self-management, continuity of care and communication between primary care providers, specialists and patients.

This approach helps to identify the resources needed to create community connections that older adults require. Data alone is insufficient. The most effective solution requires a combination of data analytics to identify patients at highest risk, business intelligence to generate interventions and alerts, and care management workflows to support outreach and interventions. 


About Dr. Jenifer Leaf Jaeger 

Dr. Jenifer Leaf Jaeger serves as the Senior Medical Director for HealthEC, a Best in KLAS population health and data analytics company. Jenifer provides clinical oversight to HealthEC’s population health management programs, now with a major focus on COVID-19. She functions at the intersection of healthcare policy, clinical care, and data analytics, translating knowledge into actionable insights for healthcare organizations to improve patient care and health outcomes at a reduced cost.

Prior to HealthEC, Jenifer served as Director, Infectious Disease Bureau and Population Health for the Boston Public Health Commission. She has previously held executive-level and advisory positions at the Massachusetts Department of Public Health, New York City Department of Health and Mental Hygiene, Centers for Disease Control and Prevention, as well as academic positions at Harvard Medical School, Boston University School of Medicine, and the Warren Alpert Medical School of Brown University.


FDA panel unimpressed with data for Alzheimer’s drug aducanumab

The FDA may have been minded to approve Biogen and Eisai’s Alzheimer’s candidate aducanumab, but its clinical advisors have little doubt that the evidence for the drug is lacking.

The much-anticipated advisory committee meeting held on Friday to discuss the marketing application for aducanumab proved to be a fractious affair, with both the companies’ data – and some of the FDA’s interpretation of it – under fire by panellists.

After hours of debate, the verdict from the experts was pretty unequivocal – 10 panellists voted against the main study supporting the drug, with just one saying they were uncertain about the data. Not one was convinced that the clinical trial results proved that the drug was effective.

The resounding rejection of the clinical data submitted in support of the marketing application for aducanumab came after the FDA published briefing documents that indicated the agency’s clinical reviewer was in favour of approval, calling the results “persuasive” despite a fairly damning assessment by the agency’s statistical expert in an appendix.

Aducanumab is vying to become the first Alzheimer’s drug designed to tackle an underlying cause of the disease, and the first new treatment for the neurodegenerative disease in almost two decades.

The FDA has been working closely with Biogen on the application and could still decide to approve the drug despite its experts’ reservations. That said, the balance of the votes makes that outcome unlikely – despite impassioned testimony during the virtual meeting by patient organizations.

The agency is due to make a decision by 7 March, and a review is also underway at the European Medicines Agency (EMA). Analysts have predicted it could become a multibillion-dollar blockbuster if approved, although at the moment that looks unlikely without another clinical trial.

An approval could also be seen as vindication for the hypothesis that tackling the amyloid plaques that are seen in the brains of people with the disease helps to slow the onset of symptoms. Many people had given up on the hypothesis after dozens of failed studies involving anti-amyloid drugs.

Biogen ran two identically-designed phase 3 studies of aducanumab – EMERGE (Study 302) and ENGAGE (Study 301) – to try to demonstrate that the anti-amyloid antibody could slow down the loss of cognitive function in people with mild cognitive impairment due to Alzheimer’s.

Last year, it called a halt to the studies after a futility analysis found it unlikely that aducanumab would show an effect on cognitive decline, but a few months later said that EMERGE was positive after all, and would form the basis of a marketing application with a phase 1b extension study – called PRIME – used as supportive evidence.

After a positive discussion of the results from Billy Dunn, acting director of the FDA’s office of neuroscience, the panel voted on three aspects of the data set.

In the first, they came down 8 to 1, with 2 uncertain, that the EMERGE trial could not be viewed on its own as providing strong evidence supporting aducanumab’s efficacy without taking into account the negative ENGAGE data.

They then voted 7 against and 4 uncertain on a question asking whether PRIME provide supportive evidence of the effectiveness of aducanumab in Alzheimer’s, before rejecting the premise that EMERGE could serve as primary evidence supporting the efficacy of the antibody.

Overall, the conclusion was that a negative interpretation of the data is just as likely as the positive one put forward by the trial sponsors, with one suggesting Biogen had shot first, and painted a bullseye later.

Biogen issued a short statement after the meeting in which CEO Michel Vounatsos said: “We appreciated the opportunity to share our data with the advisory committee, and we will continue to work with the FDA as it completes its review of our application.”

Trading in the biotech’s stock was halted ahead of the advisory committee meeting, but looks likely to be under considerable pressure when it resumes as it has been fluctuating wildly in reflection of the fortunes of aducanumab.

Biogen has a lot riding on aducanumab, as its pipeline has suffered recent setbacks including the failure of multiple sclerosis candidate opicinumab and a gene therapy for spinal muscular atrophy (SMA) at a time when big selling SMA drug Spinraza (nusinersen) is facing increased competition.

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Trials and tribulations in Biogen’s Alzheimer’s drug reviews

Regulatory reviews of Biogen’s Alzheimer’s drug aducanumab are now ongoing on both sides of the Atlantic, but debate is still ongoing about whether the data behind the drug is strong enough to support approval.

The EMA has just kicked off its review of the anti-amyloid therapy, following in the footsteps of the FDA in the US which has been looking at the drug since August, but a new analysis of the mixed phase 3 data for aducanumab argues that an additional trial should be carried out.

The paper in the journal Alzheimer’s & Dementia, led by Mayo Clinic neurologist David Knopman, says that efficacy of aducanumab “as a treatment for the cognitive dysfunction in Alzheimer’s disease cannot be proven by clinical trials with divergent outcomes.”

Meanwhile, the paper also notes that Knopman has been excluded from an FDA advisory committee meeting due to discuss the data on Friday, ahead of a decision on the marketing application due in March.

The expert – who was an investigator in the phase 3 trials of Biogen’s drug – told Reuters he was recused from the panel because of his involvement in conducting clinical trials of aducanumab.

Aducanumab – which Biogen is developing with Japanese drugmaker Eisai – was all but abandoned in 2019 after the partners decided that two phase 3 trials of the drug were unlikely to show an effect on cognitive decline in Alzheimer’s.

Shares in Biogen were hit hard, as investors lost hope that aducanumab might be rescue the almost defunct amyloid hypothesis of Alzheimer’s disease, which holds that blocking the formation of amyloid plaques in the brain could delay the onset of dementia.

Just a few months later however they said a fresh look at the results of the EMERGE and ENGAGE studies had revealed that the initial futility analysis was “incorrect.” In fact, the drug reduced clinical decline in patients with early, a chance was put down to more exposure to a higher dose in additional patient follow-up.

Some patients showed statistically significant improvements on symptoms like memory, orientation, and language, as well as being able to carry out day-to-day tasks more easily.

There’s a lot riding on the FDA and EMA reviews. If approved, aducanumab will become the first therapy to reduce the clinical decline of Alzheimer’s and to change the course of the disease, says Biogen. It would also be the first amyloid-targeting drug to reach the market, after dozens of others have failed in clinical development.

Meanwhile, aducanumab is the big hope in Biogen’s late-stage pipeline, which otherwise is looking fairly thin, at a time when the biotech is facing the loss of patent protection for its blockbuster multiple sclerosis therapy Tecfidera (dimethyl fumarate).

Knopman and fellow authors argue in the Alzheimer’s & Dementia paper that Biogen’s interpretation of data in the two trials might not be correct.

They write that they have found alternative explanations for the apparent drug benefits unrelated to the treatment, and say that while there is evidence that aducanumab was working on amyloid and other biomarkers like tau protein as expected, “no evidence was presented to correlate biomarker changes to cognitive benefits.”

They also say there were differences in the placebo responses between the two studies, which could have contributed to the divergent results.

“Our analysis supports the conduct of a third, definitive phase 3 trial with high‐dose aducanumab [that is] optimally designed and adequately powered to prove efficacy,” they conclude.

The FDA has not commented on the reasons for Knopman’s exclusion from the advisory committee meeting publicly, but in these cases there is usually a conflict of interest.

Along with his involvement in EMERGE and ENGAGE, Knopman also serves on a data safety monitoring board for a tau drug for Alzheimer’s developed by Biogen, and is an investigator in a trial sponsored by Eli Lilly and the University of Southern California.

He also performs unpaid consultancy work for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences, according to the paper’s conflict of interest statement.

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Topical Lemon Balm Lotion for Alzheimer’s

Improving cognitive performance with aromatherapy in young, healthy volunteers is one thing, but how about where it really matters? As I discuss in my video Best Aromatherapy Herb for Alzheimer’s, a group of Japanese researchers had a pie-in-the-sky notion that certain smells could lead to “nerve rebirth” in Alzheimer’s patients. Twenty years ago, even simply raising such a possibility as a hypothetical was heretical. Everybody knew that the loss of neurons is irreversible. In other words, dead nerve cells are not replaced, an important factor in neurodegenerative diseases. That’s what I was taught and what everyone was taught, until 1998.

Patients with advanced cancer volunteered to be injected with a special dye that’s incorporated into the DNA of new cells. On autopsy, researchers then went hunting for nerve cells that lit up in the brains. And, as you can see at 1:14 in my video, there they were: new nerve cells in the brain that didn’t exist just days or months before, demonstrating “that cell genesis occurs in human brains and that the human brain retains the potential for self-renewal throughout life”—something in which we can take comfort.

It still doesn’t mean smells can help, though. An aromatherapy regimen of rosemary, lemon, lavender, and orange essential oils was attempted for a month. At 1:43 in my video, you can see the trajectory of the subjects’ cognitive function and their ability to form abstract ideas starting six weeks before the treatment. Prior to the aromatherapy regimen, there was a rather steady decline, which was reversed after the aromatherapy. The researchers concluded that aromatherapy may be efficacious and “have some potential for improving cognitive function, especially in AD [Alzheimer’s disease] patients”—all, of course, without any apparent side effects.

What about severe dementia? We always hear about the cognitive deficits, but more than half of patients with dementia experience behavioral or psychiatric symptoms. Thorazine-type antipsychotic drugs are often prescribed, even though they appear to be particularly dangerous in the elderly. “Antipsychotic medication may be viewed as an easier option than non pharmacological alternatives,” such as aromatherapy. Another study examined the effect of rubbing a lemon balm-infused lotion on the arms and face of patients twice daily by caregiving staff, compared with lotion without the scent. “During the 4 weeks, significant improvements were seen” in agitation, shouting, screaming, and physical aggression, as were improved quality of life indicators, with patients less socially withdrawn and more engaged in constructive activities, compared to the unscented control. This is important because antipsychotics cause patients to become more withdrawn and less engaged. They are like a chemical restraint. The drugs can reduce agitation, too. So, aromatherapy with lemon balm “is safe, well tolerated, and highly efficacious, with additional benefits on key quality of life parameters.”

These findings clearly indicate the need for longer-term multicenter trials,” but we never had any, until…never. We still don’t have any. This study was conducted in 2002, and there have been no follow-ups. Is that a surprise? Who’s going to fund such a study: Big Balm?

I’ve produced one other video on lemon balm: Reducing Radiation Damage with Ginger and Lemon Balm. We grow lemon balm in our garden. It makes a delicious tea. Give it a try!


For more on the potential (and limitations) of aromatherapy, check out:

It’s better, of course, to prevent dementia in the first place. Learn more:

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations:

Biogen to get speedy FDA review for Alzheimer’s drug despite not using voucher to request it

Dementia or brain damage and injury as a mental health and neurology medical symbol with a thinking human organ made of crumpled paper torn in pieces as a creative concept for alzheimer disease.

Biogen and Eisai said the FDA had accepted and given priority review to their application for aducanumab. The drug will undergo an advisory committee meeting at an undisclosed date. Biogen’s stock rose 10%, but analysts had mixed opinions.

Roche doubles down on tau for Alzheimer’s, licensing UCB drug for $120m

Roche already has one Alzheimer’s candidate in its pipeline targeting tau, but has added a second via a deal with Belgian drugmaker UCB worth up to $2 billion.

The Swiss pharma group is paying $120 million upfront for exclusive global rights to UCB0107, an anti-tau antibody that is in a phase 1 trial in another disease – progressive supranuclear palsy (PSP) – but hasn’t yet started clinical development in Alzheimer’s.

UCB is retaining rights to UCB0107 in PSP, and will fund development of the drug through proof-of-concept studies in Alzheimer’s. At that point, Roche can either follow through with the license or return rights.

The drug becomes a backup to Roche’s semorinemab (RG6100), which is licensed from AC Immune and has already started two phase 2 trials in Alzheimer’s patients. One in early-stage (prodromal) patients – called TAURIEL – is due to generate results this year, and a second in patients with moderate symptoms is due to readout in 2021.

Tau is a protein that is found in cells of the central nervous system and is involved in the assembly and stabilisation of neuronal microtubules – channels used to transport substances to different parts of the nerve cell.

In Alzheimer’s the protein goes haywire, forming tangles that have been linked to cell damage and neuronal death. Tau tangles are one of the characteristic hallmarks of Alzheimer’s visible in the brain, along with amyloid plaques.

Most of the efforts of the pharma industry on funding Alzheimer’s therapies has focused on amyloid, with almost universally negative results. Some candidates remain in development, including Roche’s own crenezumab and gantenerumab, which remain in development despite negative trials.

Biogen and Eisai have already filed for approval of their amyloid-targeting antibody aducanumab, and while some analysts see the evidence for the drug as somewhat shaky, it has a chance of becoming the first disease-modifying drug to be approved for the disease.

Dozens of amyloid drugs have failed at the clinical testing stage, and as a result some drugmakers have turned their attention to tau protein as another possible therapeutic target for Alzheimer’s.

Along with Roche and UCB, other companies are working on tau. Furthest ahead is TauRx, which has a tau aggregation inhibitor called LMTX in a phase 2/3 trial (LUCIDITY) with results due in 2021 or 2022, although that drug failed to show a benefit over placebo in a phase 3 trial reported in 2016.

AbbVie has ABBV-8E12 in mid-stage testing, as does Biogen with its BIIB092 plus two other recently licensed drugs from Ionis and Sangamo. Meanwhile, Eli Lilly, AC Immune, Johnson & Johnson, Merck & Co, Anavex and Axon Neurosciences have other anti-tau drugs in early-stage clinical testing.

Roche’s head of pharma partnering, James Sabry, said the deal with UCB will “help expand our efforts on tau.”

He added: “Our commitment remains strong on exploring multiple approaches with the hope that our research and development, including this collaboration with UCB, will lead to a disease-modifying medicine that could positively impact millions of people with Alzheimer’s disease.”

UCB meanwhile says it plans to start a phase 3 trial of UCB0107 in PSP in the second quarter of next year.

PSP is a rare and progressive neurodegenerative condition that can cause problems with balance, movement, vision, speech and swallowing that also features a build-up of toxic tau in the brain.

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Roche and UCB Collaborate to Develop UCB0107 for Alzheimer’s Disease

Shots:

  • UCB to receive $120M and is eligible to receive $2B as cost reimbursement, development, and commercial milestones as well as royalties on sales of the therapies, if Roche proceeds the clinical development. Roche to get an exclusive license to develop and commercialize UCB0107 for AD
  • UCB to fund and perform a POC study in AD and, upon the availability of the results of that study while Roche has the right to progress with the development or return full rights back to UCB
  • UCB0107 is an IgG4 mAb targeting a central Tau epitope, being developed to block/reduce the spread of Tau pathology. UCB continues to develop UCB0107 in PSP, with anticipated initiation of P-III study in Q2’21

Click here ­to­ read full press release/ article | Ref: PRNewswire | Image: PharmaShots




Current Health, Dexcom Partner to Deliver Continuous, Remote Glucose Monitoring

Current Health, Dexcom Partner to Deliver Continuous, Remote Glucose Monitoring

What You Should Know:

– Current Health has partnered with Dexcom to add continuous
glucose monitoring (CGM) capabilities to its remote patient monitoring (RPM)
platform – enhancing care and improving outcomes for diabetics.

– Dexcom CGM data will transmit directly into the Current
Health wearable and platform for review by the care management and clinical
teams, improving post-discharge and chronic care of diabetes patients outside
the hospital.

– Through this partnership, Current Health is now able to
offer a complete view of patients’ health indicators, no matter where that
patient is located – a critical need as keeping patients out of the hospital is
even more important than ever with the COVID-19 pandemic. With these insights,
healthcare providers are able to proactively address issues associated with
diabetes and provide the best possible care.


 Current Health today
announced it has partnered with Dexcom to
add continuous glucose monitoring (CGM) capabilities to Current Health’s AI-powered remote patient
monitoring (RPM)
platform. By continuously monitoring patients’ glucose
levels – largely considered the fifth vital sign – the Current Health platform
will empower health systems to secure actionable and comprehensive insights
into overall patient health, resulting in improved patient outcomes and
decreased healthcare costs.

Integration Details

As part of the integration, Dexcom CGM data will transmit
directly into the Current Health wearable and platform for review by the care
management and clinical teams, improving post-discharge and chronic care of
diabetes patients outside the hospital. Dexcom and Current Health is supplied
pre-configured and ready to go out of the box with a setup time of less than 5
minutes, the patient applies Dexcom and the Current Health wearable, so
continuous vitals and continuous glucose are immediately available for review
by the care management or clinical team. The integration will be an optional
add-on for patients using the Current Health wearable, offered first to
patients with diabetes. The integration will become widely available later this
year.

COVID-19 Underscores Need for Continuous Glucose Monitoring

With an estimated 463 million people across the globe
– or one out of every 11 adults – suffering from diabetes, health systems need
insight into patients’ whole health – including glucose levels – to best manage
at-risk patients. With people with diabetes particularly vulnerable to a
variety of illnesses, including cardiovascular disease, nerve damage and
Alzheimer’s disease – not to mention COVID-19 
healthcare providers need to be able to continuously monitor glucose levels to
ensure they can proactively address issues associated with diabetes and provide
the best possible care.

“Our focus has always been on delivering the best care to people with diabetes through continuous glucose monitoring,” said Matt Dolan, senior vice president and general manager of new markets at Dexcom. “By integrating our leading CGM system into Current Health’s RPM platform, we can expand the clinical utility of our technology and also offer a more comprehensive view into a patient’s whole health. These factors together mean that more patients will get the best care possible.”


Biogen, Eisai complete submission of controversial Alzheimer’s drug. The ball is in FDA’s court now.

Dementia or brain damage and injury as a mental health and neurology medical symbol with a thinking human organ made of crumpled paper torn in pieces as a creative concept for alzheimer disease.

The FDA has 60 days to decide whether or not to accept the application. An analyst wrote that the agency accepting it with a priority or standard review may signal whether the agency is seriously considering approval or has continued reservations about the amyloid beta-targeting drug’s clinical benefit.

High Blood Pressure May Lead to Low Brain Volume

Having hypertension in midlife (ages 40 through 60) is associated with elevated risk of cognitive impairment and Alzheimer’s dementia later in life, even more so than having the so-called Alzheimer’s gene.

“It is clear that cerebral vascular disease”—that is, hardening of the arteries inside our brain—“and cognitive decline travel hand in hand,” something I’ve addressed before. “However, the independent association of AD [Alzheimer’s disease] with multiple AVD [atherosclerotic vascular disease] risk factors suggests that cholesterol is not the sole culprit in dementia.”

As I discuss in my video Higher Blood Pressure May Lead to Brain Shrinkage, one of the most consistent findings is that elevated levels of blood pressure in midlife, ages 40 through 60, is associated with elevated risk of cognitive impairment and Alzheimer’s dementia later in life—in fact, even more so than having the so-called Alzheimer’s gene.

“The normal arterial tree”—all the blood vessels in the brain—“is…designed as both a conduit and cushion.” But when the artery walls become stiffened, the pressure from the pulse every time our heart pumps blood up into our brain can damage small vessels in our brain. This can cause “microbleeds” in our brain, which are frequently found in people with high blood pressure, even if they were never diagnosed with a stroke.

These microbleeds may be “one of the important factors that cause cognitive impairments,” “perhaps not surprising[ly],” because on autopsy, “microbleeds may be associated with [brain] tissue necrosis,” meaning brain tissue death.

And speaking of tissue death, high blood pressure is also associated with so-called lacunar infarcts, from the Latin word lacuna, meaning hole. These holes in our brain appear when little arteries get clogged in the brain and result in the death of a little round region of the brain. Up to a quarter of the elderly have these little mini-strokes, and most don’t even know it, so-called silent infarcts. But “no black holes in the brain are benign.” As you can see at 2:12 in my video, it’s as though your brain has been hole-punched.

“Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed.” What’s more, they can double the risk of dementia. That’s one of the ways high blood pressure is linked to dementia.

There’s so much damage that high blood pressure levels can “lead to brain volume reduction,” literally a shrinkage of our brain, “specifically in the hippocampus,” the memory center of the brain. This helps explain how high blood pressure can be involved in the development of Alzheimer’s disease.

As you can see at 3:02 in my video, we can actually visualize the little arteries in the back of our eyes using an ophthalmoscope, providing “a noninvasive window” to study the health of our intracranial arteries, the little vessels inside our head. Researchers “found a significant association” between visualized arterial disease and brain shrinkage on MRI. However, because that was a cross-sectional study, just a snapshot in time, you can’t prove cause and effect. What’s needed is a prospective study, following people over time. And that’s just what the researchers did. Over a ten-year period, those with visual signs of arterial disease were twice as likely to suffer a significant loss of brain tissue volume over time.


What can we do about high blood pressure? A lot! See, for example:

What else can we do to forestall cognitive decline or dementia? I referenced my video Alzheimer’s and Atherosclerosis of the Brain earlier, and here are other videos that offer information on treatment and prevention:

 

In health,

Michael Greger, M.D.

PS: If you haven’t yet, you can subscribe to my free videos here and watch my live presentations: