The Advocate

February 2025: Volume 5, Issue 2

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In This Issue:

Advancing AAVs: Highlights from ASGCT’s Immunogenicity Workshop 
The Empowering Patients Summit Is Three Weeks Away! 
Senate Confirms RFK Jr. as HHS Secretary
New Article Explores Coverage and Reimbursement Challenges in Gene Therapy Access 
Executive Orders and Administrative Actions Impact CGT Field 
Legislators Consider Changes to Medicaid Program
CMMI CGT Access Model Proceeding; List of Participating States Expected After Feb. 28
Competing Budget Resolutions Advance in Congress
CGT Pipeline Grows 7 Percent in Q4 2024
Policy News

ASGCT Advocacy

Advancing AAVs: Highlights from ASGCT’s Immunogenicity Workshop 

The Class Considerations on Immunogenicity for AAV Gene Therapy Products workshop facilitated vital conversations on challenges in AAV development, including immunogenicity testing, animal models, and strategies for overcoming neutralizing antibodies. ASGCT thanks the presenters and panelists who shared their expertise and insights, along with moderators who helped guide a robust dialogue and the engaged audience who asked meaningful questions.

Members of the CGT field are deeply invested in addressing the scientific and regulatory challenges facing AAV gene therapy development. A summary of the event will be available online shortly.

The Empowering Patients Summit Is Three Weeks Away!

Join ASGCT on March 12 and 13 for Empowering Patients 2025: A Cell and Gene Therapy Summit. This is a free virtual event designed to provide patients, advocates, and additional stakeholders with knowledge to help navigate the complex CGT landscape. Through expert-led sessions and interactive discussions, you'll gain insights on everything from funding early-stage research to understanding the complexity of CGT trial design, along with regulatory pathways that aim to support rare disease drug development.

One must-attend session on March 13, “When Innovation Stumbles + Pathways Forward,” will address a critical challenge in CGT; what happens when a development program is deemed not commercially viable? Drs. Terence Flotte and Cara O’Neill will lead a dynamic discussion on why pre-commercially viable or “dropped trials” occur, how advocacy groups are impacted, and potential solutions to keep promising therapies moving forward.

This is a great opportunity to engage with experts, share experiences, and explore ways to drive CGT innovation despite potential challenges along the way. Register now to be part of these timely conversations. In advance of the Summit, visit ASGCT’s resources on the Patient Education website and subscribe to The Patient Press./p>

Senate Confirms RFK Jr. as HHS Secretary

The full Senate voted 52 to 48 last week to confirm Robert F. Kennedy, Jr. as Secretary of Health and Human Services (HHS). The HHS Secretary oversees pivotal agencies including the Food and Drug Administration (FDA), National Institutes of Health (NIH), and Centers for Medicare & Medicaid Services (CMS).

During confirmation hearings in both the Senate Finance and Health, Education, Labor, and Pensions (HELP) Committees, Senators questioned Kennedy about his views on vaccines, NIH research integrity, Medicaid and Medicare, chronic diseases, and other topics. When asked about CGTs for sickle cell disease, Kennedy affirmed his support for gene therapies, noting that “NIH should be enthusiastically supporting that kind of research.”

The newly announced Make America Healthy Again Commission, established on Feb. 13, has a stated focus on including transparency in federally funded health research, exploring the reasons behind Americans' health issues, ensuring access to healthy and affordable food, and expanding treatment options and health coverage for lifestyle changes and disease prevention. The Executive Order establishing the Commission referenced recent advances in gene therapy for Sickle Cell Disease as an example of progress in an accompanying fact sheet.

New Article Explores Coverage and Reimbursement Challenges in Gene Therapy Access

ASGCT is pleased to announce the publication of a new policy-focused article in Molecular Therapy – Methods & Clinical Development, authored by members of ASGCT's Government Relations Committee. This critical piece tackles coverage and reimbursement issues and builds upon  a companion article addressing regulatory barriers and solutions to advancing gene therapy development for rare diseases.

The latest article explores the logistical and economic challenges of commercializing gene therapies for rare diseases, including innovative payment models, patient portability issues, and aligning payer policies with FDA-approved indications. The article emphasizes the importance of reducing administrative barriers and incorporating disease-specific clinical expertise in payer coverage decisions to ensure equitable and timely access to these transformative therapies. ASGCT members are encouraged to read the full article and engage in this important conversation.

Executive Orders and Administrative Actions Impact CGT Field

The Trump Administration has issued a series of executive orders (EOs) and other administrative actions with relevance for CGTs. EOs are public directives from the President to federal agencies. Agency leaders may also enact policy changes through internal memos and other administrative adjustments. The following is a summary of key developments since the inauguration:

• Research support: A memo from the NIH Office of the Director announced that the indirect cost rate for research grants, which supports expenses like facilities and administration, will be capped at 15%. The memo indicated that the change would be effective February 10, and would apply to both future grants and those already awarded. If implemented, this would represent an estimated cut to indirect costs of approximately $4 billion a year. However, under the Further Consolidated Appropriations Act and the ongoing Continuing Resolution, NIH may not retroactively modify grants. . The attorneys general of 22 states filed a federal lawsuit seeking an injunction against this new cap; a hearing has been set for February 21. ASGCT has released a statement regarding the proposal, and affirming support for critical investments in research.

• Federal funding: A federal funding freeze ordered by the Office of Management and Budget (OMB) paused a wide range of grants, loans, and financial assistance programs until they could be reviewed by Trump Administration leaders. This prompted widespread confusion and temporary pauses in some federal funding streams, including from the National Science Foundation (NSF). Several lawsuits have led to injunctions ordering funding to be restored.

• Public communications: Another memo issued by OMB in January introduced a communications freeze for HHS and all of its constituent agencies. As of Feb. 13, some NIH study sections and other external communications have resumed.

• Regulation: A government-wide 60-day regulation freeze has been imposed until a department or agency head appointed, or designated, by President Trump can review and approve them. Another EO directs the termination of federal DEI programs. FDA's guidance on Diversity Action Plans for clinical trials was developed based on a 2022 Congressional mandate; the draft guidance text was removed from FDA’s website and then restored, but it has not been formally revoked through the Federal Register. Members of the Energy and Commerce have requested clarity on the guidance’s path forward. HHS Secretary Nominee Robert F. Kennedy, Jr. also committed to finalize the guidance during a nomination hearing. ASGCT commented on draft guidances in 2022 and 2024.  

• Reduced staffing: President Trump’s "Workforce Optimization Initiative" requires OMB to develop a plan for workforce reduction which includes the implementation of a hiring ratio of one new employee for every four departures, with exemptions for public safety, immigration enforcement, and law enforcement positions. The order directs agency heads to prepare for "large-scale" reductions in force (RIFs), particularly targeting offices not mandated by statute, including diversity, equity, and inclusion initiatives and non-essential operations. An estimated 65% of FDA staff are funded by user fees, not appropriations, and perform statutory duties. An estimated 12% of current FDA staff perform activities that are deemed necessary by implication, or for the safety of human life or protection of property. These employees are expected to be exempt from the EO according to its stated parameters.  Layoffs have been reported within CDRH, however, as well as at other HHS agencies.

• Federal workforce policies: Various EOs have directed agencies to take actions including a 90-day hiring freeze while OMB develops a workforce reduction plan (notably making no exceptions for FDA's user fee-funded positions); mandatory return to full-time office work; and reinstatement of "Schedule F" for policy-focused positions. Additionally, workers across the federal government have been offered a “buyout” with the goal of reducing total federal employee numbers.

• Medicaid: An EO revoked Executive Order 14087, which among other things had directed HHS to explore cost-reduction demonstrations through the CMS Innovation Center. Notably, the CGT Access Model scheduled to launch this year may continue under existing administrative authority.

• Global engagement: The administration has announced U.S. withdrawal from the World Health Organization, which may affect international CGT regulatory harmonization efforts; ASGCT has also previously engaged with WHO's advisory committee on genome editing.

ASGCT will continue to monitor developments across the federal government and will provide updates for our members as implementation details become available.

Legislators Consider Changes to Medicaid Program

The Trump Administration and some lawmakers in Congress are considering a wide range of changes to the Medicaid program which, if implemented, would have impacts over the next decade. Proposed reductions in the program could involve capping federal Medicaid spending per enrollee, changing the federal medical assistance percentage (FMAP) formula, or eliminating enhanced federal match rates for ACA expansion populations. If enacted, states would need to either increase Medicaid funding through their own state budgets or reduce services for enrollees. Other Congressional proposals that could impact Medicaid enrollment include the imposition of work requirements.

The proposed Medicaid cuts are tied to broader budget reconciliation efforts to offset costs from  tax cuts and border security. Reconciliation allows Congress to pass budget-related legislation with a simple majority in both the House and Senate, bypassing filibusters., bypassing filibusters.

Medicaid is a payer for innovative medicines including CGTs for rare diseases. Advanced therapies already face challenges adhering to CMS requirements and FDA labels under the current public payor system. Cuts to states’ federal Medicaid funding could further limit access by biasing patient care away from high-value, high-cost CGTs or by fully eliminating patients’ Medicaid eligibility. ASGCT supports policies that promote robust and timely patient access to gene and cell therapies, which are at the forefront of medical innovation.

CMMI CGT Access Model Proceeding; List of Participating States Expected After Feb. 28

The Cell and Gene Therapy (CGT) Access Model, is currently proceeding despite the rescission of Executive Order 14087 by President Trump. This voluntary model, designed to help state Medicaid programs cover the cost of expensive cell and gene therapies, focuses initially on sickle cell disease treatments. While the executive order that initiated the program has been revoked, at this time the model is expected to move forward as planned. The program allows CMS to negotiate multi-state, outcomes-based agreements with drug manufacturers on behalf of participating states. Applications for state participation are open until Feb. 28 proposed under the previous administration are not expected to launch following the executive order rescission.

Competing Budget Resolutions Advance in Congress

Budget reconciliation is a legislative process utilized by Congress to pass certain types of budget-related bills with a simple majority, bypassing 60-vote filibuster rules in the Senate. This process allows a party with control of the House, Senate, and White House to advance policy priorities without needing support from the minority party.

The House and Senate recently advanced differing budget resolutions for fiscal year (FY) 2025, setting the stage for potential reconciliation legislation to implement aspects of President Trump's agenda. The House resolution is more wide-ranging, proposing $4.5 trillion in new spending primarily for tax cuts, while mandating at least $1.5 trillion in cuts over ten years, with a goal of $2 trillion in reductions. It also includes a $4 trillion debt ceiling increase. In contrast, the Senate's resolution, advanced on Feb. 12, would allow for up to $517 billion in new borrowing over the FY 2025 to 2034 period. The Senate plan focuses on border security, military, and energy policies, authorizing $85.5 billion in annual spending to be offset by cuts. Unlike the House, the Senate does not address tax reform in this resolution, intending to handle it in a separate bill later this year. These divergent approaches will likely require negotiation between the two chambers to reconcile their budget approaches.

As a separate matter, the FY 2024 federal funding deadline is approaching quickly. Without action to pass a full FY 2024 budget or extend temporary funding, the government would shut down on March 14. At this time, there is not a settled path to keep the government funded.

As discussions for both FY 2024 funding and FY 2025 reconciliation unfold, the outcome will impact a range of sectors. That includes the cell and gene therapy field, as funding for critical medical research and regulatory bodies like the FDA could be affected by the overall budget decisions.

CGT Pipeline Grows 7 Percent in Q4 2024

ASGCT has released the Q4 2024 Gene, Cell, and RNA Therapy Landscape Data Report in partnership with Citeline. This field-wide report covers the therapeutics pipeline, clinical targets, developer progress, and more. 

In Q4 2024, significant milestones in gene, cell, and RNA therapies included new approvals in all three categories in the U.S.: Aucatzyl, a CD19 CAR T-cell therapy for leukemia; RegeneCyte, an allogeneic stem cell therapy for blood disorders; and Tryngolza, for lipoprotein lipase deficiency. Across 2024, there were four gene therapy approvals, two non-genetically modified cell therapy approvals, and three RNA approvals. The pipeline grew by 7% in 2024, matching growth rates from previous years, with an 83% rise in pre-registration gene therapy programs in Q4.