A year ago, then FDA-commissioner Scott Gottlieb and Director of the Center for Biologics Evaluation and Research Peter Marks issued a statement on the influx of new applications for gene and cell therapies. Calling this new era a “turning point,” Gottlieb and Marks said that it’s “similar to the period marking an acceleration in the development of antibody drugs in the late 1990s, and the mainstreaming of monoclonal antibodies as the backbone of modern treatment regimens.”
One particular paragraph caught my attention at the time: “For example, we intend to propose guidance to address how the accelerated approval pathway may be used when the target of the gene therapy product is an underlying monogenetic change that causes a serious disorder not addressed by available therapy. In these cases, the gene therapy could offer the potential to alter or cure the underlying genetic defect that gives rise to, and causes the advance of, a disease.”
As someone who has been involved in rare disease advocacy for years, it reinforced how we’re living in the best of times for helping families and friends impacted by debilitating diseases. One-time curative treatments, many of which will be made possible through accelerated approval, provide us with a new outlook on our loved ones’ chances of survival.
This said, it’s clearly been difficult for companies, advocates and the FDA together to help turn advanced science into breakthrough treatments. I’m writing this blog to try and create awareness around and help bridge the gap of understanding of gene therapy development pathways that could be a source of inefficient trial designs at the expense of patients. Now is the time for clarity and consistency, especially when engaging the FDA and, in turn, help inform decisions that are made by both the agency and individual companies.
Recently, I was sitting in the audience at a scientific workshop hosted by EveryLife Foundation and viewed a video in which a baby diagnosed with the devastating disease X-linked myotubular myopathy (XLMTM) seemed to recover after a gene therapy treatment was initiated. This video was also accompanied by corresponding strong expression and functional results from a clinical study. In a disease that caused children to die of global weakness and respiratory failure by the age of two, these babies were not only surviving, but thriving, without the use of mechanical ventilation.
But then the company that manufactures the therapy announced that the FDA review division was advising them that the next study should be placebo-controlled. This begged a natural question: Why would the division be giving advice to proceed with a placebo-controlled study when, based on the previous statement, an accelerated approval pathway would seem appropriate?
While I’m mindful that the FDA couldn’t talk about any specific program, I reached out to Peter Marks to get a sense of how the agency was ensuring that its statement was being applied equitably to all programs. For those who know Peter, he’s always been a proponent of acting in the best interest of both science and the patient. Fortunately, he confirmed what I interpreted last January: If the effect size is large – either by expression or function that is blatantly obvious and not a miniscule amount – a potential accelerated approval pathway should exist. It’s important that everyone involved in advocacy and companies developing new treatments know this.
A few other takeaways from my conversation with him:
- Patient advocates should not be afraid to engage the FDA with questions or concerns. While the agency cannot discuss specific products under review, they are very willing to listen to the patient point of view.
- Similarly, it’s important that advocates voice their concerns to drug companies if there’s any doubt that companies aren’t exploring the most efficient available development pathways.
- In turn, companies should always feel free to challenge agency advice – and specifically escalate inconsistent decisions – if they seem to run counter to sound scientific reasoning and broader FDA direction.
- The relationship between the FDA and companies should be viewed as a marriage. Open and honest dialogue about issues and concerns facilitates a good relationship and, moreover, best helps advance product development to the benefit of patients in need.
Bottom line: The FDA is receptive to pushback and companies should be as well. And when there’s inconsistent advice being provided, it’s critical that we escalate.
The aforementioned case in which use of a placebo was recognized for an illness fatal to very young children serves as an object lesson for those of us who advocate for those we love. When a different approach should be taken, we need to speak up.
Science is bringing new hope to those in our community, but we don’t have the luxury of being reticent and shy when it comes to the crafting of pathways that will deliver those medical miracles to us. We need to focus on how interactions between patients, companies and the FDA happen efficiently and in a timely manner.
Stay tuned for updates as I continue to learn more and feel free to leave comments based on what you’re hearing. For most of us (and our loved ones), there is only one shot to get this right.
About The Author
Jenn McNary is a trusted voice in the rare disease community, as a mother, public speaker and fierce advocate. Her work in the rare disease space as a thought leader earned her the Ryan’s Quest Ryan’s Hero award in 2013, a nomination for the Global Genes Champion of Hope award in 2014, and the prestigious 2017 Meyer- Whalley instrument of change award. Formerly as the director of outreach and advocacy at a Massachusetts based non-profit foundation, she was responsible for the organization of the largest FDA advisory committee hearing in history, with over 1000 duchenne advocates, families, clinicians and researchers in attendance. There are currently only three drugs approved for Duchenne, Exondys51, Vyondys53 and Emflaza, though in various roles, Jenn was involved in the approval process for all three. Jenn has unique experience in the drug development field, as a parent of children enrolled in the clinical trials, an advocate engaging with the regulators and as a consultant helping to develop programing for patients. Currently, Jenn is consulting in the biotechnology space with an expertise in caregiver/patient engagement, including bringing the patient voice to drug development and solving barriers to access. Her other activities include serving as the Founder of One Rare, a non-profit formed to meet the needs of young adults with rare and chronic conditions and raising her four children in Massachusetts.