The P-IIb study will evaluate three dose levels of ION449 (once a month, SC) vs PBO and will enroll ~108 patients aged 18-75yrs., who have LDL-C levels b/w 70-190 mg/dL and are receiving moderate/ high-intensity statin therapy
The P-I study results demonstrated dose-dependent mean reductions in circulating plasma PCSK9 and LDL-C levels of >90% and ~70% respectively
AstraZeneca granted $20M as a milestone to Ionis for the initiation of the P-II study. ION449 is antisense therapy designed to reduce blood cholesterol levels in patients with dyslipidemia by targeting PCSK9
Click here to read full press release/ article | Ref: PRNewswire | Image: The New York Times
The concept of targeted protein degradation presents revolutionary drug development opportunities and is anticipated to bring about a paradigm shift in modern healthcare. While conventional medicines, such as small molecule inhibitors and monoclonal antibodies, address fewer than 20% of the proteome, targeted protein degradation offers a unique means to tap into the rest of the vast, unexplored proteome.
The science behind this innovation revolves around the use of specially designed small molecules that are capable of recruiting the ubiquitin-proteasome system (UPS) to selectively eliminate a target protein, via proteolysis.
Over the years, significant progress has been made towards understanding the physiochemical and biological properties of these bifunctional molecules. In fact, a variety of other chemical entities and molecular glues have been developed for the treatment of a variety of clinical conditions. The growing popularity and interest in the therapeutic potential of these molecules is evident across modern scientific literature (500+ related articles on NCBI’s PubMed portal), and from social media chatter (4,000+ tweets posted on the platform, Twitter, over the last three years).
Current pipeline of targeted protein degradation-based drugs
During our research, we came across close to 90 targeted protein degradation-based therapeutics that are being investigated for a wide variety of application areas. The first targeted protein degrader, called proteolysis targeting chimera (PROTAC), was developed about a decade ago, and is currently accounting for more than 30% of the pipeline drugs. These are being developed primarily to treat advanced oncological disorders (such as acute myeloid leukemia, breast cancer, lung cancer, multiple myeloma, and prostate cancer). A few drugs are also being evaluated for the treatment of non-oncological indications.
ER+/HER2- is the most popular target protein, as per the current drug development focus in this domain. Specifically, in the clinical pipeline, about 10 drugs are being developed to target ER+/HER2-; examples include (in decreasing order of clinical phase of development) elacestrant (phase III), SAR439859 (phase II), G1T48 (phase I/IIa), LSZ102 (phase I/Ib), ARV-471 (phase I), AZD9833 (phase I), AZD9496 (phase I), D-0502 (phase I), GDC-9545 (phase I) and GDC0927 (phase I).
Most of the molecules that we came across are being evaluated as both monotherapies and combination therapies (56%), whereas around 26% are being investigated as monotherapies alone. Given that majority of the therapeutics are small molecules, the most preferred route for the delivery of targeted protein degradation-based therapeutics is oral route (over 85%), followed by the intravenous route (~11%).
During our research, we came across more than 60 clinical trials that have been registered across different geographical locations for evaluating targeted protein degradation-based therapeutics. Examples of the most active industry players in this domain include (in decreasing order of number of clinical trials) Celgene, Samus Therapeutics, Medivir, AstraZeneca, Radius Pharmaceuticals, Genentech, Sanofi, Arvinas, CellCentric, and InventisBio.
For further information on this emerging domain, check out the report here.
There is a school of thought that says now is not the time to criticise the government and its scientific advisers about the way they have handled the Covid-19 pandemic. Wait until all the facts are known and the crisis has subsided, goes this thinking, and then we can analyse the performance of those involved. It’s safe to say that Richard Horton, the editor of the influential medical journal the Lancet, is not part of this school.
An outspoken critic of what he sees as the medical science establishment’s acquiescence to government, he has written a book that he calls a “reckoning” for the “missed opportunities and appalling misjudgments” here and abroad that have led to “the avoidable deaths of tens of thousands of citizens”.
In being shielded, he has learned the true significance of key workers… ‘they are making society work’
TEDMED Meetups, uniquely designed conversations, engage the entire TEDMED community to share their individual perspectives and voices to help improve humanity’s health. Read on to view some of the details of these captivating conversations taking place at TEDMED 2020.
Meetup 1 Tuesday, March 3rd, 8:00 am- 8:45 am
Climate and Culture, A Health Equity Conversation Hosted by RWJF and facilitated by Malik Yakini, an RWJF Health Equity Expert Speakers: Cheryl Holder, Jyoti Sharma, and Thijs Biersteker Description: When we consider human health, we must consider climate health. Whether it is the impact the climate has on the social determinants of our health, the depletion of essential resources like water caused by a changing climate, or how we can harness art to better connect ourselves to our environment, each Speaker in this Meetup has a unique understanding of our connection to climate and its impact on our health. Facilitated by Malik Yakinin, a leader of the movement to bring great equity to the global food system, this Meetup will explore how climate shapes our culture and impacts our health.
The Good Life Hosted by the TEDMED Community and facilitated by Lucy Kalanithi, TEDMED EAB Member and TEDMED 2016 Speaker Speakers: Kevin Toolis and Louise Aronson Description: It’s one of the oldest philosophical questions: What is the good life? As we confront aging bodies and our own mortality, how do we embrace the beauty and dynamism of our lives in ways that enhance and expand our health and wellbeing? Hosted by former TEDMED Speaker and Stanford Medicine internist, Lucy Kalanithi, this Meetup will explore how reframing the stages of elderhood and embracing death as part of life can help us cultivate the good life.
The Future of Health Hosted by Deloitte and facilitated by Jennifer Radin, Life Sciences & Health Care Principal at Deloitte Speakers: Anupam B. Jena, Michel Maharbiz, and Suchi Saria Description: Data is all around us and within us. With progressive innovation comes new insights to advance health and medicine. This Meetup will explore how natural experiments can reveal important phenomena in our everyday lives, how tiny ultrasound activated implants can provide real-time information about our physiology, and how machine learning is saving lives in our medical system. Led by Deloitte, this Meetup allows us to wonder what the future of health will look like.
Compassionate Care Hosted by Astellas Oncology and facilitated by Shontelle Dodson, Senior Vice President for Health Systems at Astellas Speakers: Lisa Sanders and Shekinah Elmore Description: When faced with a difficult diagnosis or living with a serious illness, we must often manage a great deal of uncertainty. Whether it is helping to find a diagnosis or guiding us through the uncertainty of an unexpected health concern, health care providers and caregivers play an integral role in ensuring that patients can find fulfillment even in their most uncertain moments. Shontelle Dodson, a health systems leader at Astellas, will guide this discussion about the importance of infusing more compassion into care.
Meetup 2 Tuesday, March 3rd, 11:15 am- 12:00 pm
A Culture of Health, A Health Equity Conversation Hosted by RWJF and facilitated by Aletha Maybank, an RWJF Health Equity Expert Speakers: Joseph Shin, Sandro Galea, and Wanda Irving Description: How do we create a culture of health in asylum settings and within systems teeming with racism? How do we create a culture that breeds love and not hate? How do we cultivate a culture of inclusivity and equity in healthcare? Aletha Maybank, the American Medical Association’s first Chief Health Equity Officer, will lead this conversation about bringing to light the darkest parts of our society in order to ensure that everyone has a fair and just opportunity to be as healthy as possible.
Personalizing Digital Health Hosted by Abbott and facilitated by Toni Nosbush, DVP of Global Product Development at Abbott Hive Innovators: Claire Novorol of Ada Health; Leah Sparks of Wildflower Health; and, Jon Bloom of Podimetrics Description: Today’s technology allows healthcare to be personalized like never before. In this Innovator Meetup, conversation will center around the trend in digital health that creates space for tailored health experiences. While these Innovators’ have varied focuses – ranging from family planning, to patient centered care coordination, and diabetic foot ulcers – the common thread is their focus on effective, reliable, and personalized care experiences. Guided by Toni Nosbush, a leader in global product development at Abbott, this Meetup will explore how better communication between doctor and patient, facilitated by personalized health tools, patients can receive tailored care to become and stay healthy.
New Age Diagnostics Hosted by the TEDMED Community and facilitated by Laura Indolfi, TEDMED 2016 Hive Innovator Hive Innovators: Andy Beck of PathAI; Gabe Kwong of Glympse Bio; Niamh O’Hara of Biotia; William Dunbar of Ontera Description: In this Hive Innovator Meetup, you will have the chance to learn about cutting edge life science innovation. With today’s scientific advancements, new diagnostic models have emerged to detect and intercept disease faster than ever. With AI-powered pathology and diagnostics, a closer look at the epigenome, and miniaturized biological sensors, these Innovators are reimagining disease diagnostics. Their technology will shape a future in which illness can be identified accurately, quickly, and reliably every time. TEDMED 2016 Hive Innovator Laura Indolfi will lead this conversation about the possibilities of new age diagnostics.
New Models of Mental Health Care Hosted by the TEDMED Community and facilitated Pat Salber, TEDMED Community Member Hive Innovators: April Koh of Spring Health; Peter Hames of Big Health; Paula Searcy of Sana Health Description: Understanding mental health care has become an important theme of our time. With a steady rise in the prevalence of mental health conditions, we must leverage new tools and approaches to keep people healthy. In this Meetup, Innovators will discuss varying models of care that work to improve mental health. You will learn about medical devices, digital health products, and systems level tools that leverage new technology to improve mental health conditions like PTSD, sleep disorders, anxiety, depression, and more. Pat Salber, Editor-in-Chief of The Doctor Weighs In, will facilitate this Meetup about the potential of new models of mental health care to lead to personalized, tailored, and effective care we have not seen before.
Meetup 3 Tuesday, March 3rd, 1:00 pm – 1:45 pm
A Just World Hosted by the TEDMED Community and facilitated by Pam Belluck, TEDMED EAB Member Speakers:Homer Venters, Laurie Hallmark, and Yasmin Hurd Description: From combating the opioid epidemic with nontraditional solutions, to transforming legal representation and advocacy for people with serious mental illness, to restoring health justice for incarcerated individuals, the Speakers in this Meetup are improving health for some of society’s most vulnerable populations. Pam Belluck, Pulitzer Prize winning science writer for The New York Times, will facilitate this discussion about what it means to create a fair and just world.
Health Techquity, A Health Equity Conversation Hosted by RWJF and facilitated by Margaret Laws, an RWJF Health Equity Expert Hive Innovators: Kevin Quennesson of Braid.Health; Mercy Asiedu of Calla Health; Taylor Justice of Unite Us Description: “Techquity” describes the use of technology to create a more equitable world. In this Meetup, Innovators will share how they are making healthcare more accessible and equitable by leveraging new-age technology. From a medical device that empowers women to understand their cervical health, to a platform connecting vulnerable populations to social service providers, and an AI-powered tool that makes radiology accessible to all people, these Innovators are using technology to fill major gaps in today’s healthcare system. Margaret Laws, an RWJF TEDMED 2020 Health Equity Expert and head of HopeLab, will facilitate this conversation about how ‘techquity’ can help health become more equitable, faster.
The Power of Medical Knowledge Hosted by the TEDMED Community and facilitated by Jeff Karp, TEDMED EAB Member; TEDMED 2014 Speaker Hive Innovators: Andrew Le of Buoy; Jane van Dis of Maven; Sunny Williams of Tiny Docs Description: Should medical knowledge be reserved for trained professionals, or can it lie with patients and communities? The Innovators in this Meetup will speak to the importance of empowering patients with medical knowledge that is accurate, reliable, and tailored to their unique needs. TEDMED 2014 Speaker Jeff Karp will lead this conversation examining how medical knowledge can be delivered in various forms–telemedicine, virtual communities, AI-powered assistants, or even “caretoons” — all while serving the tailored needs women, children, underserved populations, or your average health consumer.
Mapping Human Health Hosted by the TEDMED Community and facilitated by Zen Chu, TEDMED Community Member Hive Innovators: Andy Blackwell of Eight Billion Minds; Katharine Grabek of Fauna Bio; Nancy Yu of RDMD; Ted Schenkelberg of Human Vaccines Project Description: With the rise of technology, we have the opportunity to capture health data like never before. In this Meetup, Innovators will demonstrate the ways in which data can be mapped, across conditions, to better understand, analyze, and reimagine human health. Zen Chu of MIT’s Hacking Medicine Initiative will lead this Meetups about mapping trends around mental health, immunity, rare diseases, or even animal genomics, and what it means for the future of data and human health.
Meetup 4 Tuesday, March 3rd, 4:15 pm – 5:00 pm
Youth and Truth, A Health Equity Conversation Hosted by RWJF and facilitated by Kellan Baker, an RWJF Health Equity Expert Speakers: Anne Marie Albanno, Cheryl King, Francis X. Shen Description: Dealing with anxiety, mood disorders, developing brains, sexuality, and social pressures is just one aspect of the challenges that come with the transition from adolescence to young adulthood. How can we better understand the developing brain in order to ensure that all individuals receive access to the treatment and care they require? Facilitated by Kellan Baker, a leading researcher of how reshaping socioeconomic and political determinants of health can create greater health equity for transgender populations and other marginalized groups, this Meetup will focus on how we as a society can best support our young adults.
Meaning Making and Memory Hosted by the TEDMED Community and facilitated by Kafui Dzirasa, TEDMED EAB Member and TEDMED 2017 Speaker Speakers: Anne Basting, Beatie Wolfe, Frederick Streeter Barrett Description: French philosopher, Rene Descartes’ famous words “I think, therefore I am” is a powerful statement about a sense of awareness within ourselves. In this Meetup, we explore our brain as a dynamic and complex organ by evaluating creative stimuli that lead to surprising reactions in patients with cognitive impairments and by understanding mind altering experiences that allow us to grow and to heal. Led by former TEDMED Speaker, Kafui Dzirasa, this Meetup challenges us to consider the meaning of life when memories fade.
The Social Side of Health Hosted by Humana and facilitated by William Shrank, Chief Medical and Corporate Affairs Officer at Humana Speakers: Cheryl Holder and Jonathan Gruber Description: Health, as we know, is more than just medical. Our health is impacted by economics, the healthcare system, the environment, and our social surroundings. Whether it’s understanding the impact of a changing climate on population health or structuring our health systems to make healthcare better and more accessible, how we think about the social side of healthcare matters. Humana’s Chief Medical and Corporate Affairs Officer, William Shrank, will guide this discussion.
Trust in Medicine Hosted by the U.S. Pharmacopeia (USP) and facilitated by USP’s CEO Ron Piervincenzi Speakers: Heidi Larson, Katherine Eban, and Ralph Nader Description: We all deserve medicines that we can trust, but globally, many lack access to high-quality medicines and the health impacts can be detrimental. In this Meetup, hear from TEDMED Speakers who are examining the conditions in which low-cost generic medicine are made, are advocating for consumer rights to help ensure we have access to safe medicines, and are working to restore the public’s trust in the vaccines that help keep us safe. Facilitated by Ron Piervincenzi, the CEO of the U.S. Pharmacopeia, this conversation will dive into how leading thinkers and doers are working to build and maintain trust in medicine.
Meetup 5 Wednesday, March 4th, 8:00 am – 8:45 am
Infectious Disease and Innovation Hosted by the TEDMED Community and facilitated by Celine Gounder, TEDMED EAB Member Speakers: Heidi Larson, Leor Weinberger, and Matt Hepburn Description: What does it take to fight disease and are we prepared for the next pandemic? Infectious disease specialist and TEDMED Editorial Advisory Board member Celine Gounder will lead this Meetup conversation examining the systems necessary to address pandemic threats – from global vaccine uptake to the development of novel therapies to deprive infectious disease.
Novel Approaches to Big Problems, A Health Equity Conversation Hosted by RWJF and facilitated by Aletha Maybank, an RWJF Health Equity Expert Speakers: Cheryl King, Francis X. Shen, and Thomas Abt Description: Big problems require big solutions. The speakers in this Meetup are developing and implementing big, novel solutions to some of society’s most serious issues. From curbing the rising rates of teen suicide, to fighting for justice in the legal system, to reducing urban violence, these individuals are committed to saving the lives of some of our most vulnerable populations. Aletha Maybank, the AMA’s Chief Health Equity Office, will guide the conversation and help us to understand how equity plays a key role in finding solutions to these issues.
A Vision for a Healthier Future Hosted by Geisinger and facilitated by Geisinger Leadership Speakers: Fred Moll, Gokul Upadhyayula, and Suchi Saria Description: We live in a world where robotics, bioimaging, and machine learning are becoming increasingly common terms. This Meetup will explore the possibilities of constantly emerging technologies with capabilities to transform healthcare tools as we currently know them. Geisinger will lead this Meetup discussion about the role of technology in creating a healthier future.
Science and Storytelling Hosted by the TEDMED Community and facilitated by Nadja Oertelt, TEDMED EAB Member and TEDMED 2017 Hive Innovator Speakers: Amit Choudhary, Michel Maharbiz, Zuberoa Marcos Description: Whether it’s conveying the nuances and implications of a tool as powerful as CRISPR, understanding molecular and physiological states, or harnessing the power of storytelling in presenting scientific advances to keep the world moving forward, how we tell the story of science is integral to reaching and inspiring a broad audience and making the impact needed to shape a healthier humanity. Nadja Oertelt, TEDMED 2017 Hive Innovator and Co-Founder of Massive Science, facilitates this conversation about science and storytelling.
The TEDMED 2020 theme is Make Way For Wonder, and we are looking forward to convening our Community and embracing the wonders of our times, the astonishing accomplishments, incredible possibilities, and extraordinary potential for the future. So, we were thrilled when the United States Pharmacopeia (USP) decided to celebrate its 200th Anniversary with TEDMED. After all, today’s wonders are built upon a strong foundation of scientific discovery. And, humanity is especially eager for those innovations that will help people everywhere live longer and healthier lives. In anticipation of USP’s presence at TEDMED in March, we talked with Ronald T. Piervincenzi, Ph.D., chief executive officer, about the organization’s history, its current work, and its approach to building trust in the future of medicine, supplements, and foods.
TEDMED: We’re excited to have you and USP join the TEDMED Community, especially on the occasion of such a monumental milestone – USP’s 200th anniversary.
Ronald T. Piervincenzi: Thank you. I’m thrilled to introduce USP to TEDMED’s audience and look forward to meeting attendees in Boston in March.
TM: What made you choose TEDMED to celebrate this milestone anniversary?
RP: Today, we are observing an unprecedented transformation in healthcare. USP’s 200-year legacy is built on trust and confidence in healthcare systems and anticipating and responding to emerging health challenges. Our founders joined together in 1820 to protect patients from a prevalence of poor-quality medical products. The backdrop today is different in scale, geography, modalities and many other factors. But the value of our work is the same. We are exploring how to build trust in future medical breakthroughs. There are many in the TEDMED community we can learn from and engage with as we imagine what the future holds.
TM: That’s exactly what TEDMED is all about! Let’s dive in. What is a pharmacopeia and what does USP do?
RP: Simply put a pharmacopeia is an official publication that includes a list of medicinal drugs and contains how those medicines are to be prepared, directions for their use, and assays to assess medicinal quality. The United States Pharmacopeia–National Formulary, which USP publishes, is the official quality standard for medicines marketed in the U.S. It is also used in over 140 other countries. USP is the leading independent scientific nonprofit organization that collaborates with the world’s top experts in health and science to develop quality standards for medicines, dietary supplements, and food ingredients. Through our standards, advocacy and capability building, USP helps increase the availability of quality medicines, supplements and food for billions of people worldwide. As the world gets smaller and more connected, quality issues affect everyone. Diseases travel. Drug resistance grows. Fake medicines kill. The foundation of quality we’re building helps address these and other global health challenges. Whether decreasing the prevalence of substandard and poor-quality medicines or helping to curb antimicrobial resistance, we’re there across 10 global sites working to protect the health of people all over the world.
TM: This seems like a very modern approach to medicine. Why did the U.S. need a pharmacopeia in 1820?
RP: Today, people trust U.S. medicines to be among the safest in the world but that wasn’t always true. In 1820, the U.S. was a new country. Medicines were made individually and differently by physicians or apothecaries. There were no regulations or more importantly, standards, to ensure that what you received in one city was the same as another. A medicine’s strength, quality, and even its identity varied widely depending on where it was made. Simply put, before our founding in 1820, there was no way to ensure that what was on the medicine label was what was actually in the bottle. Our founders—11 independent, forward-looking physicians— were concerned about this lack of uniformity and acted to protect patients from poor-quality medicines. Three of our founders were not only physicians, but also U.S. Senators—they were the voice that the U.S. needed to ensure the quality of medicines Americans used. They established the U.S. Pharmacopeial Convention, which published the first U.S. Pharmacopeia. A great deal has changed since our founding but the importance of having quality standards for medicines and other new therapies remains—now, our work is much more global.
TM: This year’s TEDMED theme, “Make Way for Wonder,” explores how medicine and healthcare is changing. Is that a theme that resonates with you?
RP: Absolutely. Wonder and scientific discovery makes medical breakthroughs possible. But trust makes them popular. More than 800 independent volunteer scientists contribute their expertise to develop and approve USP’s standards. They help to build trust by setting clear quality expectations for medicines, dietary supplements, and foods. In turn, USP standards help manufacturers worldwide bring more quality and affordable products to market, which benefits people everywhere. A recent Johns Hopkins University study found that on average, drugs with a USP public quality standard had approximately 50% more generic manufacturers compared with medicines without such a standard. The study also found that quality standards helped facilitate pharmaceutical competition and reduce prescription drug costs in the U.S.
TM: How does a 200-year-old organization prepare for the future?
RP: New technologies and treatments—precision medicine, digital therapeutics, 3D printing, immunotherapy, gene and stem cell therapies, and artificial intelligence—have arrived or are on their way. As we prepare for dramatic breakthroughs, we must work to ensure trust and quality are established as a part of these advances. Unfortunately, trust broadly is in a precarious position across sectors. Our history has taught us that for an innovation to become a widespread reality, both quality and trust are critical to its broad acceptance. USP together with hundreds of our stakeholder organizations and partners are already working to build confidence in future breakthroughs and to anticipate and address where the gaps will be. We know that when a USP public standard is available, we help manufacturers be better able to adopt the new technology, which is often a significant cost savings. In addition to conducting workshops and roundtables on topics such as cell and gene therapies and digital therapeutics, USP is working with the MIT Center for Collective Intelligence and more than 100 leaders from health and science worldwide to explore the developments and role that trust will play in shaping people’s health between now and 2040. We will explore the project’s findings from this “Trust CoLab” with the TEDMED 2020 Community.
TM: We’ll look forward to learning more about the Trust CoLab. Until then, what else should the TEDMED Community know about USP?
RP: I mentioned our volunteer scientists earlier. I invite TEDMED community members who are committed to making the world healthier, being scientifically rigorous, and working independently from politics or the private sector, to consider becoming a Champion of Trust. They can learn more by visiting our website or by stopping by the USP Lounge in the Social Hub at TEDMED. I also encourage everyone to also learn more about USP’s past, present and future and opportunities for other collaborations with us at www.usp.org/200?utm_source=rss&utm_medium=rss.
TM: Thank you, Ron and very best wishes on the beginning of USP’s third century.