The Advocate

March 2024: Volume 4, Issue 3

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In This Issue:

Watch Dr. Terence Flotte's Testimony Before U.S. House Subcommittee
FDA Liaison Meeting Presentations Focus on AAV + Genome Editing
Society Weighs in on Advanced Manufacturing for CGTs 
Flexible Solutions Needed for Patient Access, Society Responds on ERISA
FDA Incorporates ASGCT Suggestions in Final Guidances
Appropriations Move for FY24 + Kick Off for FY25 
Policy News


ASGCT Advocacy

Watch Dr. Terence Flotte's Testimony Before U.S. House Subcommittee

On February 29 ASGCT’s Vice President, Dr. Terence Flotte, testified before the House Energy and Commerce Committee’s Subcommittee on Health in a hearing titled “Legislative Proposals to Support Patients with Rare Diseases.” A recording of the hearing is now available to watch online. The Society appreciated the opportunity to represent the cell and gene therapy (CGT) field on Capitol Hill for Rare Disease Day.

Dr. Flotte shared insights on the challenges and opportunities in advancing CGT development for rare diseases. A majority of rare diseases are genetic in origin; Dr. Flotte explained how CGTs are uniquely situated to address these types of conditions. Flotte also emphasized the urgency in addressing access barriers for patients with rare diseases from preclinical research through commercialization. He highlighted the critical need for proactive policies to enable CGT development. His testimony underscored the importance of collaboration among stakeholders and the necessity for a flexible regulatory framework to expedite safe and effective treatments for the most vulnerable patient populations. 

 A blog post detailing Dr. Flotte’s testimony is available here.  

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FDA Liaison Meeting Presentations Focus on AAV + Genome Editing

ASGCT held its sixth annual FDA Liaison Meeting on Feb.23. Society members gave two presentations to FDA on significant topics in the field, followed by a presentation from Dr. Nicole Verdun, Director of CBER”s Office of Therapeutic Products (OTP). View the full summary of the event along with ASGCT’s and FDA’s slide presentations. 

The Society’s first presentation to FDA, Class Considerations for Determining Safety and Efficacy Outcomes for AAV Gene Therapies, focused on safety and efficacy for AAV gene therapies. A key theme was the need to bring the field together to resolve questions and work toward FDA guidance on vital aspects such as immunogenicity and integration. The second ASGCT presentation discussed On- and Off-target Analysis for Genome Editing. Presenters addressed considerations for on-target analysis, a case study on biological de-risking, and CMC considerations. 

Dr. Verdun then presented staffing updates for the OTP super-office. She also touched on her vision for the office, and discussed the various pilot programs that aim to accelerate development. Dr. Verdun reviewed the START PilotRDEA Program, CoGenT International Pilot, and forthcoming Platform Technologies Designation. The director and staff also engaged with the Society on the CRDP Pilot Program.  

These Liaison Meetings serve as a key communication point between ASGCT members and the Agency reviewers. ASGCT appreciates FDA’s candor and willingness to come together to discuss these complex issues. 

Society Weighs in on Advanced Manufacturing for CGTs 

The Society submitted comments on the Advanced Manufacturing Technologies (AMT) Designation Program draft guidance. While the pipeline of cell and gene therapies (CGTs) has been growing exponentially, the adoption of advanced manufacturing practices leveraging novel technologies has been slow. Traditionally, the FDA has provided binding feedback about manufacturing technologies during a biologics license application (BLA). This creates uncertainty for product sponsors who would need to make costly manufacturing changes to leverage a novel technology - while running the risk that it may not be approved by the FDA. The AMT pathway, mandated by Congress, would decouple the product from the advanced manufacturing technology and expedite applications with a designated AMT.  

ASGCT’s response noted the creation of a product agnostic pathway is an important step toward the adoption of new manufacturing technologies. If implemented properly, the AMT Designation Program could help address the challenges currently facing the manufacturers and sponsors of CGTs, as there is a current imbalance in how CDER and CBER products are treated in the assessment of manufacturing. Current FDA policy does not allow a BLA to incorporate information about drug substance, drug intermediate or drug product through referencing a drug master file (DMF). DMFs are the main way that propriety information from contract manufacturers, or other third parties, can be shared with the Agency without having to disclose it to a drug sponsor. Recently, FDA finalized a rule that codified this practice in regulation.  

Be sure to check out our new blog post for more specifics on ASGCT’s comments. The Society is excited to see the Agency tackling one of the biggest bottlenecks in CGT development – the manufacturing process – and will continue to update on activity in this space. 

Flexible Solutions Needed for Patient Access, Society Responds on ERISA

Chairwoman Virginia Foxx of the House Committee on Education and the Workforce recently posted a request for information about the Employee Retirement Income Security Act (ERISA); ASGCT responded to the final section on specialty drug coverage.  

The Society’s response focused on several key themes. The letter highlighted the potential of CGTs to improve patients’ and caregivers’ lives, and the challenges of patient access in a healthcare system designed for chronic treatment over months or years, rather than one-time transformative therapies with a frontloaded cost. Challenges with forecasting and patient portability between health plans can make those difficulties more acute. ASGCT generally supports efforts to explore flexible, innovative solutions that protect patient access, including the use of value-based agreements (VBAs). 

Employers or health plans may turn to a number of different strategies to manage risk and control costs; our comments called out several strategies of concern. Those include trends to exclude gene therapies from coverage or put undue limitations on eligibility, as illuminated in our 2023 white paper on Medicaid coverage policies, and opaque, clinically irrelevant prior authorization requirements that can result in lengthy treatment delays. ASGCT believes transparency would help start to address both issues; the Society has proposed parallel public dashboards incorporating information about a) real-world CGT coverage and b) payers’ prior authorization requirements. 

As conversations continue in this space, ASGCT will keep advocating for policies that can facilitate the development and accessibility of transformative treatments. 

FDA Incorporates ASGCT Suggestions in Final Guidances

ASGCT recently contributed to positive changes in FDA’s regulation of two genetic therapy modalities. In 2022 the Society commented on two draft guidances that have now been finalized; we are pleased to see FDA incorporate many of ASGCT’s recommendations in the final versions of those two guidances. While a full comparison is available online, in summary: 

Human Gene Therapy Products Incorporating Human Genome Editing 

  • ASGCT's suggestions prompted FDA to make several changes to the final guidance. Among other things, the Society successfully advocated for:  

    • Regulatory flexibility for one-time use materials (like Master Cell Banks) 

    • Language explicitly supporting accelerated approval for GE products 

    • Flexibility in assay selection to identify editing events 

Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products 

  • While the final guidance largely remained unchanged from its draft form, FDA addressed several of ASGCT's comments, including:  

    • Removing unfeasible requirements on evaluating previously administered CAR T cell levels 

    • Adjusting language regarding vector characterization 

    • Acknowledging the need for clarity on timelines for communicating manufacturing changes, which may be addressed in future guidance 

The Agency hosted webinars for each of these new releases to discuss key considerations in the final guidances. Recordings of the sessions on genome editing and CAR Ts are now available.  

FDA’s Center for Biologics Evaluation and Research (CBER) has published also published their full 2024 Guidance Agenda. This outlines the guidance documents the Agency plans to release in 2024 and indicates their regulatory priorities for the coming year. The Society is especially watching for the release of two new draft guidances required under the Food and Drug Omnibus Report Act (FDORA) of 2022: one governing a new Platform Technologies Designation, and another on diversity action plan guidances. ASGCT is currently working on a response to the recently-released Potency Assurance for CGT Products draft guidance.  

Appropriations Move for FY24 + Kick Off for FY25 

Congressional leaders passed legislation earlier this month to fund some government agencies, including FDA, until early fall 2024. In the legislation, Congress requested FDA provide a briefing on the Advanced Manufacturing Technologies Designation draft guidance, and urged additional clinical trial guidance from FDA. Guidance on platform technologies and diversity plans for clinical trials are still outstanding from Food and Drug Omnibus Reform Act (FDORA) of 2022. The budget also proposes reauthorizing and modernizing key user fee programs, crucial for maintaining efficient drug review processes and expediting access to new therapies, including cell and gene therapies. In addition, the FDA's budget for FY 2024 includes provisions to support innovation in oncology clinical trials and foster collaboration with international regulatory authorities. 

The minibus, formally known as the Consolidated Appropriations Act 2024 (H.R.4366; H.Res.1061),  allocated $6.72 billion in total funding for the FDA, including $3.52 billion in discretionary funds.  

The remaining 6 appropriations bills expire by Friday, March 22, unless Congress acts. This includes funding for Labor-HHS, which provides for the National Institutes of Health. ASGCT will be tracking that final set of bills as they move through Congress

Looking Ahead Fiscal Year 2025 
The President's FY25 budget request was released on March 11. The request includes prioritizing and strengthening public health capacity, advancing Cancer Moonshot goals, and enhancing data modernization platforms through the FDA. ASGCT staff will monitor the President’s priorities and will provide updates when available. 


Sneak Peek: Policy Sessions at the Annual Meeting

New at this year’s Annual Meeting: we’ve introduced program tracks with suggested pathways to streamline your schedule with sessions directly relevant to your interests. Some of the sessions included in the Regulatory & Government Affairs track are below; the full online agenda is updated daily. 

  • Companion Diagnostics (CDx) for AAV-based Gene Therapies: With the dramatic growth in the number of gene therapy clinical trials, more sponsors are realizing the challenges in navigating the requirements of developing a CDx in parallel with the clinical development of their gene therapies. The goal of the session is to understand the regulatory requirements and basics of CDx development, and the unique challenges for AAV gene therapies. 

  • Enabling Analytics for Decentralized and Point-of-Care Manufacturing: This session will focus on the opportunities and challenges of alternative manufacturing models, especially decentralized and point of care approaches. Presenters will share a regulatory overview of the different models, a deep dive into analytics and how to enable them, and lessons from companies that are working to put these models into action. 

  • The Role of Government in Ensuring Equity of Access to CGTs: Ensuring that patients can access FDA-approved CGTs underpins the future sustainability of the development ecosystem. This session will discuss how we think about value, current health system models to support patient access, and the role of the government and public-private partnerships. 

Registration is now open for both in-person and hybrid attendance. Join your colleagues and our expert line up of presents as we tackle critical issues around payment policy, commercialization, regulatory science, and more!  

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 has released a new report on the utility of the Rare Pediatric Disease (RPD) Designation and Priority Review Voucher (PRV) Program looking at the number of designations, progress made in various disease treatments, and the impact on drug development timelines and processes.  

  • The Government Accountability Office (GAO) published a report noting that the Advanced Research Projects Agency for Health (ARPA-H) has not finalized an advisory committee charter intended to prevent duplicate research between its funded projects and other parts of NIH. ARPA-H has been consulting committee members individually and plans to hold biannual meetings to address this issue. 

  • On February 28, the White House released an Executive Order (EO) directing a number of federal agencies to create new constraints on the movement of bulk data, with a focus on personal data, and US Government-related data. The constraints in the EO are intended to prevent “countries of concern” from gaining access to this data. 

  • A pair of bills in Congress, S.3558/H.R.7085, would prohibit federal contracting with biotechnology providers deemed to be “connected to foreign adversaries.” The Senate version was advanced out of the Committee on Homeland Security & Government Affairs on March 6. One of the companies listed in the Senate bill, WuXi AppTec Co., plays a significant role in US biopharma research, development, and manufacturing. 

  • Congress has opted not to include reforms targeting pharmacy benefit managers (PBMs) in the current federal funding packages, despite bipartisan interest. Both the House and Senate have been working on PBM reforms, with proposals focusing on transparency, flat service fees in Medicare, and banning practices like spread pricing. 



Register for the 27th Annual Meeting

May 7-11, 2024 | Baltimore, MD

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