Dr. Peter Marks Clarifies FDA’s Approach to Gene Therapies After CRL for Hemophilia A Treatment

By Jennifer McNary, mother of two sons with Duchenne muscular dystrophy, patient advocate and founder of One Rare.

For all the incredible progress we’ve made in the area of gene therapy, we are still very much in the pioneer days. While two directly administered gene therapies have been approved by the Food and Drug Administration and are having a real impact in the lives of patients and families, hundreds of potential treatments are working their way through rigorous clinical trials with the hope of many more FDA approvals in the coming years. I, for one, am keeping a close eye on developments big and small. My interest is deeply personal as I have two boys with Duchenne muscular dystrophy, a rare and life-threatening disease that has limited treatment options. I am also a patient advocate for all patients with rare disease.

Unfortunately, close watchers of gene therapy are at a distinct disadvantage. Our wealth of experience with traditional medicines does not neatly translate to what we’re seeing science produce today. You see, few things about gene therapies are comparable to traditional medicines – from how they are made, studied and evaluated to how they are, ultimately, delivered to patients.

In this uncharted territory, it is natural to look for deeper meaning in every clinical trial success or failure, every patient outcome and FDA decision. This is why I recently reached out to Peter Marks, M.D., Ph.D., director of the Center for Biologics Evaluation and Research (CBER), to discuss CBER’s position on the development of gene therapies after the surprising complete response letter (CRL) sent to the maker of the gene therapy intended to treat hemophilia A. Everyone in the rare disease patient community wants to understand what, if anything, it meant for the hundreds of other gene therapies in the pipeline. I didn’t want to speculate, so I went directly to the source.

Right away, I was reassured to hear from Dr. Marks that although he could not discuss the CRL, “nothing has changed when it comes to the pathway to approval of gene therapies for diseases with unmet need.” He made a point to emphasize that the agency is ever more committed to this area of medicine knowing the promise it holds for patients who have no good options right now.

However, I still wanted to better understand how the gene therapy for hemophilia A was different from some of the other gene therapies being studied, like those for sickle cell disease and Duchenne muscular dystrophy. Dr. Marks reminded me that while hemophilia A qualifies as a rare disease, there are multiple very effective therapies available to treat it. This was not the case for spinal muscular atrophy, one of the diseases with an FDA-approved gene therapy. In cases like SMA, where there is a very high unmet need, the FDA’s assessment of benefit and risk is different. Dr. Marks was very clear on this point: “when the agency can help save the lives of children, it will do everything in its authority to do so assuming sufficient evidence of safety is there.” Dr. Marks also made it clear that the expedited drug development program used by the maker of the SMA gene therapy will still be utilized by CBER for other rare diseases.

Durability is another area of concern for the patient community after the hemophilia CRL because the FDA asked for further data on its long-term effects of the gene therapy. Many advocates and experts jumped to the conclusion that the FDA has “changed the goal posts” and may now require long-term data for all gene therapies. If true, this would substantively delay the availability of many life-changing treatments for thousands of patients waiting for these transformative therapies. Here again, Dr. Marks put my mind at ease. He reiterated that, “speaking in general, for diseases that have limited alternatives, nothing has changed.” His rationale is again grounded in the unique nature of gene therapies. “They are not trivial,” he noted. “They create lasting change in the body, so when there are existing approved therapies that potentially allow a normal life span, it is critically important to know more about how a gene therapy works over time. Conversely, when no other options are available, or the available options are associated with less than optimal outcomes, the FDA wants to get the treatment in the hands of those patients in need as quickly as possible.”

I came away from my conversation with Dr. Marks confident, optimistic and more informed. There are whole patient communities out there who are desperately waiting for the arrival of an effective gene therapy for their disease. Those communities should know that the recent CRL will have no impact on the development of those therapies. We have a partner in the FDA, a partner that is working hard to pave the way so that hundreds of thousands of patients with genetic diseases can live longer and healthier lives.


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The Institute for Gene Therapies advocates for a modernized regulatory and reimbursement framework that encourages the development of transformative gene therapies and promotes patient access. 

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