How Will Cuts to FDA and NIH Impact Gene Therapy Clinical Trials and Rett Syndrome Research?

Are the current gene therapy clinical trials impacted by or at risk from the financial cuts in the US federal agencies?

The clinical trials sponsored by Neurogene and Taysha are funded by the companies and not federal money. This means the financial cuts taking place should not, in the short term, directly affect the funding available to conduct the current trials taking place.

In the long term, decisions being made in DC may impact the companies’ future decisions.

 

How could the cuts and changes at the FDA impact current and future gene therapy clinical trials?

Before answering this question it’s important to understand what the FDA’s role is in gene therapy clinical trials.

The FDA’s Role in Trials

Gene therapy products are reviewed and approved by the Center for Biologics Evaluation and Research (CBER) within the FDA, and specifically the Office of Therapeutic Products (OTP) within CBER.

The FDA is responsible for ensuring that gene therapies are safe and effective. Before trials can begin the FDA reviews the Investigational New Drug (IND) application which includes lab and animal safety data, manufacturing process and quality control of the gene therapy product, and the design of the proposed clinical trial. Through this review process the FDA evaluates whether the gene therapy is reasonably safe and has sufficient evidence to support testing in people.

Once the trial starts, the FDA has oversight to ensure patient safety and advise on appropriate determinations of efficacy. If any safety concerns arise or as new safety data become available, the FDA can require changes or, if necessary, halt the trial with a clinical hold.

If the development program, which typically involves several trials, is successful, the company submits a Biologics License Application (BLA). The FDA then reviews the efficacy and safety data, long term follow-up plans which are particularly critical for gene therapy, manufacturing and quality assurance.

Companies can interact with the FDA by requesting formal meetings throughout the clinical development process. You can learn more about the type of meetings available to companies on the FDA website.

Furthermore, the FDA provides certain programs with additional opportunities for interactions. One such program is the Regenerative Medicine Advanced Therapy Designation, which both Taysha and Neurogene have, and Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program, which Neurogene has.

FDA Cuts

As you can see from the above explanation, the FDA plays a critical and active role in gene therapy drug development. It is therefore crucial that the FDA has sufficient, experienced staff to undertake its responsibilities.

The recent cuts have resulted in a 20% decrease in FDA staff including people in leadership positions at CBER such as Peter Marks, Director, who led the division, and Julie Tierney, Deputy Director, as well as Chief Medical Officer, Hilary Marston.

The loss of key people in leadership positions with decades of subject matter expertise who drive the approval process is concerning. Another significant concern is the possibility that the review and approval process is slowed due to staffing cuts which could delay access to transformative therapeutics.

Biotech companies have raised the alarm by submitting a joint letter to Senator Cassidy, the chair of the Senate Health, Education, Labor and Pensions Committee, to “quickly preserve and restore its core functions.”

 

Will the resignation of Peter Marks, Director of CBER impact the Rett community?

Dr. Marks joined the FDA in 2012 as Deputy Director for CBER and became Director in 2016. CBER is responsible for vaccines, blood supply and gene therapies. He stepped down as head of CBER last month and his resignation letter is available online.

The loss of Peter Marks is a major blow to rare disease and to all working in the gene therapy space and the broader genetic medicine field. Dr. Marks was a champion of rare diseases and a vocal advocate for patient access to novel therapies.

There is no evidence that the current administration has any issues with genetic medicines. We hope that Dr. Marks’ replacement will share his devotion and creative problem-solving qualities to rare diseases like Rett syndrome.

 

If the FDA cuts pose problems to U.S. trials, could Rett trials continue in other countries like Canada or the UK?

Yes. In fact, one possible outcome could be that companies conduct clinical trials outside the US more often.

 

Is Rett Research affected by the NIH cuts?

The NIH funds the basic science that fuels the discoveries that end up becoming medicines. Every Rett researcher in the US either currently benefits or has benefited from NIH funding. Most major discoveries can trace their roots back to work that was funded by the NIH.

The threatened cuts to NIH indirect costs, grants and staffing will likely have a negative impact on all NIH-funded research, including Rett research. Some of the impact is already being felt with many academic institutions enacting hiring freezes. As the US becomes a more challenging place to do science researchers may decide to go elsewhere. In fact Europe and beyond are making it clear that they would welcome US scientists. Simply put, the US risks losing our status as a leader in research and a magnet for top scientific talent.

When academic institutions and scientists are preoccupied about funding and filled with uncertainty,they cannot devote their full attention to science.

RSRT funding to academic labs continues undisturbed including funding to labs outside the US.

 

Are other avenues, for example the RNA editing programs at ProQR, impacted by the cuts and resignations at the FDA?

ProQR does not receive NIH funding or other federal dollars. The Rett programs are being funded by ProQR and RSRT and are not at risk.

However, when ProQR and any other biotech companies are ready to submit applications for clinical trials, the situation at FDA will weigh into their decision-making process of where to conduct trials.

 

Is there anything I can do to voice my concern?

The development of life saving medications, including gene therapies, is important to all of us, regardless of our political perspective. If you are concerned that the current cuts at FDA and NIH may harm patients and your loved one in particular, please call your US representatives and senators.