The Advocate

December 2024: Volume 4, Issue 12

Want to stay up to date on news and events relevant to patients, caregivers, and others affected by rare diseases? We just launched a brand new newsletter!

Subscribe to The Patient Press

In This Issue:

New MTMCD Article Explores Regulatory Challenges for Rare Disease Gene Therapies
Watch Our Latest Congressional Briefing on HIV
Lyfgenia, Casgevy Manufacturers Will Participate in CGT Access Model
Explore ATMP Research in South America On Demand
Events
Policy News

ASGCT Advocacy

New MTMCD Article Explores Regulatory Challenges for Rare Disease Gene Therapies

ASGCT’s Government Relations Committee has authored a new article titled Optimizing Regulatory Frameworks for Gene Therapies in Rare Diseases: Challenges and Solutions. The publication addresses the significant challenges in developing gene therapies for rare and ultrarare diseases, where only 5% of conditions currently have FDA-approved treatments despite affecting millions of patients globally.

The article critically examines the fundamental misalignment between traditional regulatory approaches and the unique characteristics of gene therapies for rare diseases. Key challenges highlighted include:

Complex clinical trial design for small, heterogeneous patient populations
Limitations in current accelerated approval pathways
Challenges in chemistry, manufacturing, and control (CMC) processes
The need for more specialized rare disease expertise within regulatory agencies

In response to these challenges, the authors propose several solutions to better accommodate gene therapies within existing regulatory frameworks:

Adopting a holistic approach to evaluating evidence
Fully leveraging the mechanism of action of gene therapies
Maximizing platform approaches to development
Enabling more iterative approaches to manufacturing requirements

The authors emphasize the urgent need for regulatory policies that can keep pace with scientific advancements while maintaining rigorous safety standards. This article is part of a broader effort to support regulations that enable innovation and provide hope to patients with rare diseases. A companion piece addressing rare disease payment policy challenges is forthcoming in the new year. ASGCT is excited to bring these new resources to Capitol Hill to advocate for policy reforms that enhance CGT development – especially for rare disease.

Watch Our Latest Congressional Briefing on HIV

Watch this recent briefing featuring (clockwise from top left) Paula Cannon, Paul Edmonds, Margarita Valdez Martínez, Boro Dropulic, and Matt Gardner.

On Dec. 4, ASGCT hosted a virtual briefing, Cell & Gene Therapy Approaches for HIV, bringing together researchers, policymakers, and a patient advocate to discuss the potential of cell and gene therapies (CGTs) to revolutionize HIV treatment. The briefing was held following World AIDS Day. The event highlighted the promise of CGTs to address limitations of current treatment options, and advances toward curative solutions.

The briefing featured insights from ASGCT’s President, Dr. Paula Cannon, along with Drs. Boro Dropulic, Matt Gardner, and patient advocate Paul Edmonds. Dr. Cannon outlined the challenges of fully eradicating latent HIV infection, despite the effectiveness of antiretrovirals (ARTs) in suppressing viral loads. Dr. Dropulic presented progress in CAR T-cell therapies for indications beyond cancer; these modified immune cells may be used to target and eliminate HIV-infected cells. Dr. Gardner shared his research on AAV vectors designed to produce sustained antibody responses, effectively creating an "antibody factory" within the muscles of the body. Finally, Paul Edmonds provided a compelling personal perspective as a patient who has been cured of HIV through a bone marrow transplant from a donor with a CCR5 Delta 32 mutation, emphasizing the benefits that a curative treatment option could bring.

ASGCT remains committed to advocating for research and policy solutions that accelerate CGT advancements for HIV and ensure equitable access to these innovations. This event serves as a platform to engage policymakers for continued progress in CGT development and access. You can watch the full briefing on ASGCT’s YouTube channel, along with prior Congressional briefings on gene editing, hemophilia, and CAR Ts.

Lyfgenia, Casgevy Manufacturers Will Participate in CGT Access Model

CMS announced it has reached agreements with the manufacturers of the two approved SCD therapies on a value-based outcomes arrangement, which will serve as the foundation for their CGT Access Model. States can apply to participate, and CMS will administer the program for those that opt in, including overseeing financial reconciliation. The model's focus on outcomes-based agreements is designed to overcome the challenges that Medicaid programs face with high upfront therapy costs, promoting broader adoption of gene therapies. The program will begin in 2025, with states joining on a rolling basis. While CMS has provided a framework for participation, the success of the model will depend on the willingness of states to adopt it and whether it can effectively improve access to these transformative therapies.

Explore ATMP Research in South America On Demand

(From left): Moderator Virginia Picanço-Castro talks with speakers María Verónica López and Carlos Javier Alméciga-Diaz during the event.

A recent webinar hosted in partnership with ABTCel-Gen spotlighted the latest developments and scientists working in AMTP research across South America. Dr. María Verónica López from Instituto de Lua in Buenos Aires showcased how her team is developing oncolytic adenoviruses to tackle unmet needs in cancer treatment. Meanwhile, Dr. Carlos Javier Alméciga-Diaz from Pontificia Universidad Javeriana in Colombia discussed innovative gene and cell therapy strategies for metabolic disorders, including non-viral approaches that make these therapies more accessible in resource-limited regions. Watch the recording to explore these exciting advancements and their potential to transform lives globally.

Events

Free Next Month: New FDA-partnered Workshop on AAV Gene Therapies + Immunogenicity

ASGCT and FDA are partnering to present a critical scientific workshop addressing one of gene therapy's most pressing challenges: immunogenicity in AAV-based treatments. Class Considerations on Immunogenicity for AAV Gene Therapy Products: Assessing Current Practice and New Data will convene virtually on Jan. 22 and 23, 2025, from 9 a.m.-1 p.m. ET. The workshop will bring together experts from industry, academia, and FDA to tackle complex questions surrounding immune responses to AAV vectors.

Register for Empowering Patients 2025: A Cell and Gene Therapies Summit

Coming this spring: A new, free, virtual event hosted by ASGCT on March 12-13, 2025. This event will be two half-days of educational material geared toward foundation leaders, patients, and caregivers to provide timely information to support their CGT journey. It will feature educational sessions and engaging discussions on the CGT landscape, exploring the unique challenges impacting patient communities at various stages of the CGT pipeline. Register today!

Policy News

The FDA's Center for Biologics Evaluation and Research (CBER) Office of Therapeutic Products (OTP) hosted a virtual town hall on Dec. 12 to discuss best practices for regulatory interactions with OTP throughout the product development lifecycle. A recording will be posted online shortly.
FDA has released a draft guidance addressing frequently asked questions related to cellular and gene therapy product development. The guidance spans multiple disciplines, including regulatory review, CMC, pharmacology/toxicology, clinical, and clinical pharmacology. ASGCT is reviewing the document and looks forward to providing comments to support regulatory frameworks that advance safe and effective CGTs.
The agency also released new draft guidance for sponsors on the accelerated approval pathway, which outlines the agency's policies and procedures for eligibility, endpoints, confirmatory trials, and withdrawal processes.
CMS released the final version of the 2025 Hospital Outpatient Prospective Payment System. Directly relevant to the CGT field, CMS finalized plans to exclude some cell and gene therapies from the typical payment bundle for services. The final rule makes the change permanent, while the proposed rule had floated the policy for only 2025. ASGCT supported that change in our comments on the draft rule.
CMS has released the final 2025 Physician Fee Schedule including several key changes, such as a 2.93% reduction in the conversion factor used to calculate payments and updates to drug policies related to the Inflation Reduction Act. ASGCT previously commented on the draft rule.
The U.S. Department of Health and Human Services (HHS) Centers for Medicare & Medicaid Services (CMS) has released a new resource: CMS Sickle Cell Disease (SCD) Health Care Provider Toolkit: Resources for Health Care Professionals to Support Individuals with SCD .
ASGCT is excited to announce the addition of selected policy positions to our Patient Education webpage. These resources are designed to help patients, advocates, and caregivers better understand key policies that may shape their community’s journey with cell and gene therapies.
FDA's Rare Disease Endpoint Advancement (RDEA) Pilot Program is accepting proposals through December 31, 2024, to support novel efficacy endpoint development for rare disease treatments. Sponsors admitted to the program gain enhanced interaction with FDA experts and review divisions on endpoint development.
The U.S. Government Accountability Office (GAO) has released a report evaluating FDA's efforts in rare disease drug development and approval. Key findings highlight FDA’s collaboration with patient groups to enhance staff expertise, the use of flexible evidence requirements to address challenges like small patient populations, and the creation of the Rare Disease Hub to improve coordination between CDER and CBER.