Rare diseases are individually rare, but cumulatively common. Each disease affects only a small percentage of the population, but worldwide almost 10% of every person alive has a rare disease. That’s about 750 million people. Many of these diseases are monogenic (caused by a defect in a single gene) and can be severely debilitating and life-threatening. Historically, patient groups have been the principal advocates in raising awareness about these diseases, promoting national and international support. They have also driven relevant research programs, and in the field of genetic medicine these patient-advocate groups have been inordinately successful in driving monogenic diseases towards a viable therapy.
Simon Frost’s daughter Annabel has an ultra-rare neurological monogenic disease called Alternating Hemiplegia of Childhood, or “AHC”. The disease affects one in a million people, and the worldwide patient population is less than 1,000. AHC is characterized by sudden attacks of paralysis, seizures and spells of reduced consciousness like epilepsy, low muscle tone like cerebral palsy, movement problems like Parkinson’s, and neurodegeneration like Alzheimer’s.
Like many other patient-advocates, Simon decided to lead a community-driven initiative to find therapies rapidly. Unlike many others, he decided that to be effective he needed to learn the science of the disease. He studied the molecular and cellular mechanisms of AHC, and the phenotypic spectrum in patients. He developed and funded animal and cell models of the disease. He is leading a collaborative effort to provide whole genome sequencing to all patients, and natural history studies to gather longitudinal data. He has identified therapeutic options, especially focused on genetic medicines, and has developed and patented an AAV-mediated gene therapy for AHC. He and collaborating scientists have donated all intellectual property to the three largest AHC foundations in the world, with a goal to keep this genetic medicine cheap or free for patients.
In this talk, Simon discusses the challenges of understanding and diagnosing an ultra-rare disease, the constant fear of living with a “human timebomb”, and the immediate and unprecedented opportunities to address rare monogenic diseases as a community, as a nation, and as humankind.
Innovative regulatory pathways for cell and gene products have accelerated product development and approval allowing patients in need to access transformative therapies. However, the shortened development timeline has exerted significant pressure to accelerated CMC development.
One of the biggest challenges is to develop, characterize, and validate the manufacturing process under these compressed clinical development timelines while ensuring comparability between process versions and maintaining the link to clinical data. In the past few years, several cell and gene therapy products have overcome this challenge and successfully launched new CGTPs. This session will provide the challenges industry is facing and approaches to speed up the CMC development. Perspectives from regulators will help set the expectations of CMC acceleration and pathways to facilitate innovation.
Specifically, the session will demonstrate how risk assessments are leveraged to guide process development activities for these products to ensure that the CGTP can be manufactured commercially and meet the CQAs established during registration trials.
Given the COVID-19 global pandemic, there is a lot of work being done rapidly develop a SARS-CoV-2 vaccine. A human vaccine is essential for long term protection of high-risk individuals and health care workers. Traditional approaches to prophylactic vaccine development (e.g., attenuated strains of viruses or heat-inactivated viruses) have lengthy development timelines to establish safety and efficacy. This session will introduce the challenges with vaccine development in the face of a global pandemic and will provide some examples of where nucleic acid-based vaccines can be developed on rapid timelines. Technical talks will focus on two approaches that are being used today to develop vaccines for SARS-CoV-2 vaccines. In addition to speed to clinical testing, these approaches have the additional benefit of leveraging a platform nucleic acid technology that has potential to be scaled rapidly to allow for greater reach globally.
The maturing of Cell and Gene Therapy products provides an opportunity to serve patients with options for treatment where none have previously existed. In the past few years, several cell and gene therapy products have gained regulatory approval in the US and EU. The number of products in clinical development in the US continues to increase and many of these products have potential for accelerated regulatory pathways. Manufacturers of cell and gene therapy products must tackle technological challenges under the pressure of short timelines resulting from streamlined clinical development. This session will focus on the key hurdles facing CMC professionals as product development programs move the into the later stages of process development and scale-up. How do we build a robust control strategy that is meaningful, sustainable and able to support the demonstration of process consistency as programs move through to commercialization.
Developmental allogeneic cell therapeutic products are varied and diverse with indications ranging from cancer to GvHD. With the manufacturing and economic challenges of autologous cell-based products, emerging technologies are accelerating development of off the shelf allogeneic cell therapeutic products, which may provide some advantages over autologous patient-specific therapies. Allogeneic therapies can be manufactured with testing/quality control in advance of patient treatment need and are often amenable to manufacturing scale up rather than costly scale out often required by autologous products. In this session, unique developmental challenges for early, mid- and late-phase products will be conveyed. Additionally, challenges from the regulator perspective specific to allogeneic products and lessons learned from a recently approved product will draw focus to issues important to regulatory agencies.
Comparability is a significant challenge for advanced therapies due to issues such as complexity of the products, limited amounts of material available for testing, patient-specific variability, and short shelf life. In addition, in many cases early clinical success is driving shortened development timelines that impact the timing of manufacturing changes. This session will focus on some of the challenges and strategies to address comparability for advanced therapies. The session will address both recent regulatory updates related to comparability and sponsor experience addressing comparability.