The Advocate

April 2024: Volume 4, Issue 4

In This Issue:

Third Installment of CGT Science Series Addresses Recent CMC Guidance
Society Requests Clarity and Direction on Potency Assurance Strategy for CGTs
Watch Our Congressional Briefing on Gene Editing
FDA Approves First Treatment for Metachromatic Leukodystrophy
Congressional Hearing on Employer-sponsored Insurance to Discuss CGT Coverage
Biden's Budget Request Calls for Increased Funding for FDA, NIH
Events
Policy News

ASGCT Advocacy

Third Installment of CGT Science Series Addresses Recent CMC Guidance

On March 29, FDA hosted the third Cell and Gene Therapy (CGT) Science Series, a quarterly seminar series focused on scientific topics related to cell and gene therapy products. The CGT Science Series is intended to foster scientific exchange between the Biotechnology Innovation Organization, ASGCT, and the Center for Biologics Evaluation and Research (CBER) review staff on a variety of topics that span the CGT product lifecycle.

The third episode of the series featured Dr. Andrew Byrnes, the Director of the Division of Gene Therapy 1 at FDA-CBER. Dr. Byrnes has over 20 years of experience at FDA in CMC review and regulatory policy for cellular and gene therapy products. His presentation focused on recent CMC guidance for cell and gene therapies, specifically the Manufacturing Changes and Comparability and Potency Assurance guidance documents. Dr. Byrnes discussed CMC as a facet of risk management, and encouraged a robust understanding of product mechanisms of action and critical quality attributes when making manufacturing changes. A blog post is available here.

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Society Requests Clarity and Direction on Potency Assurance Strategy for CGTs

The Society has submitted comments to the FDA concerning the draft guidance on Potency Assurance for Cell and Gene Therapy (CGT) Products. Recognizing the rapid growth of the CGT field and its potential to offer transformative therapies, the response highlighted the critical role of potency assays in evaluating product effectiveness. However, comments also identified challenges related to assay complexity, variability, and regulatory inconsistencies.

In the comment letter, ASGCT highlighted three key points. First, the Society urged FDA to explicitly acknowledge that the degree of potency assurance should be phase-appropriate. The Society stressed that potency assays critical in late-stage development may not be feasible early in clinical development. Second, ASGCT advocated for FDA to be open to risk-based selection on the number and type of assays. Finally, the Society recommended that FDA’s proposed potency assurance strategy should align with existing quality systems.

Overall, ASGCT emphasized the need for clarity and flexibility to ensure effectiveness while minimizing undue burden on developers, aligning with the Society’s mission to advance gene and cell therapy to alleviate human disease. For more information, read the blog here.

Watch Our Congressional Briefing on Gene Editing

On April 4, ASGCT hosted a bicameral briefing, Gene Editing Technologies: Transforming Rare Disease Care. ASGCT members educated Congressional staff on the potential for gene edited therapies to address unmet medical need. The briefing gave an overview of gene editing techniques and applications, a discussion of the clinical trials process, and a deep dive into why these technologies can be an important tool for the rare disease patient community. Speakers included:

Jeffrey Chamberlain, PhD, University of Washington
Fyodor Urnov, PhD, University of California Berkley
Janice Chen, PhD, Mammoth Biosciences
Matthew Porteus, MD, PhD, Standford University Medical School
Amy Raymond, PhD, Worldwide Clinical Trials

The landscape of gene editing therapies is rapidly evolving. With FDA's approval of a gene-edited therapy for sickle cell disease, ASGCT is fulfilling a critical need to inform decision-makers and legislators about the transformative potential of gene editing.

FDA Approves First Treatment for Metachromatic Leukodystrophy

In a landmark decision, the FDA granted its first-ever approval for a gene therapy to treat early onset metachromatic leukodystrophy (MLD) in children. Orchard Therapeutics' Lenmeldy (atidarsagene autotemcel) offers new hope for patients diagnosed with pre-symptomatic late infantile, early juvenile, or early symptomatic early juvenile MLD. This is a rare disorder caused by a mutation in the gene responsible for encoding the enzyme arylsulfatase A (ARSA). Lenmeldy utilizes the patient's own stem cells, modified to deliver the functional enzyme, potentially halting disease progression.

This approval is a significant advancement in the fight against MLD. The Society has been circulating the news with relevant Hill offices and external contacts. Following the approval, ASGCT’s President Dr. Jeffrey Chamberlain recently shared more information on the exciting science behind this Lenmeldy, and what this means for patients with MLD.

Congressional Hearing on Employer-sponsored Insurance to Discuss CGT Coverage

Yesterday the House Commitee on Education and the Workforce Committee held a hearing for the 50th anniversary of the Employee Retirement Income Security Act (ERISA). A recording of the hearing is available.

Earlier this year the Committee issued a request for information (RFI) about ERISA-governed health care plans, including coverage of specialty drugs like CGTs. ASGCT’s response to the RFI emphasized the potential of CGTs to improve patient outcomes and highlighted obstacles in accessing these therapies within a healthcare system designed for chronic treatments rather than one-time transformative therapies. Concerns were raised about strategies employed by employers or health plans to manage costs, such as excluding gene therapies from coverage or imposing restrictive eligibility criteria. ASGCT advocates for transparency and innovative solutions, including value-based agreements (VBAs), to ensure patient access to these transformative treatments.

Biden's Budget Request Calls for Increased Funding for FDA, NIH

President Biden submitted his budget request to Congress last month, kicking off the federal appropriations process for fiscal year 2024-2025 (FY25), which officially begins October 1. While this is only a request, and Congress holds the purse strings, it does give insight into the administration’s upcoming priorities and areas of focus. The Department of Health and Human Services Budget in Brief outlines increases for both FDA and the National Institutes of Health (NIH).

For FDA in FY25, the President’s request included a total of $7.2 billion – just under a 5% increase over FY24 levels. This includes $3.7 billion in budget authority funding, and an additional $3.5 billion from existing user fees. The budget request outlines plans for modernizing FDA’s review processes, securing national supply chains, and encouraging lower drug costs through generics and competition.

NIH’s budget justification requested $50.1 billion for the Institutes. Just under $1.5 billion of the total request is earmarked for mandatory Cancer Moonshot research. Separate from this topline number is a request for $1.5 billion in discretionary funding for the Advanced Research Projects Agency for Health. The justification specifically referenced advances in gene therapy for sickle cell disease, and calls for additional investment in biomedical research.

The next step is for the House and Senate Budget Committees to draft budget resolutions based on the President's budget request and their own priorities. These resolutions establish the overall spending levels and revenue targets for the upcoming fiscal year. Budget resolutions do not require the President's signature and do not become law; they serve as guidelines for the appropriations process. It is unclear when those initial resolutions will be drafted, but ASGCT will be watching the process closely.

Events

Register Now to Catch Policy Sessions at the Annual Meeting

Government relations and regulatory professionals won’t want to miss our policy-focused sessions during the 27th Annual Meeting May 7-11 in Baltimore, MD and virtually! Visit our interactive program to learn more about sessions on value/outcomes-based payment efforts, companion diagnostics, enabling CMC analytics, decentralized manufacturing, global regulatory convergence, and more. Register now before rates increase next month!

Save the Date for the 2024 Policy Summit

Mark your calendars! The 2024 Policy Summit has been confirmed for September 23-24 at the Westin Washington, DC Downtown Hotel. Be sure to check back for an updated agenda this spring.

Policy News

FDA recently expanded the labels for the CAR-T therapies Carvykti and Abcema to include earlier treatment for multiple myeloma patients who have received at least one prior line of therapy.
CBER launched the Rare Disease Endpoint Advancement (RDEA) Pilot Program in September 2023 to expedite rare disease drug development. Submissions for the program are accepted quarterly, with one eligible proposal chosen per quarter. The deadline for this quarter's applications is June 30.
The Office of Management and Budget (OMB) announced a revised policy directive on maintaining, collecting, and presenting data on race and ethnicity. These revisions are intended to foster more accurate and useful race and ethnicity data across the Federal government. Finalization of that directive may also enable the release of the final FDA guidance on diversity in clinical trials.
On April 2 the Department of Health and Human Services (HHS) released a white paper entitled “Policy Considerations to Prevent Drug Shortages and Mitigate Supply Chain Vulnerabilities in the United States.”  The white paper includes recommendations intended to address drug shortages, including a proposed program that would impact Medicare payments to inpatient hospitals.  
Fewer than half of the cancer drugs granted accelerated approval by the FDA between 2013-2017 showed clinical benefit in confirmatory trials after more than five years of follow-up, according to findings presented at the American Association for Cancer Research Annual Meeting.