A new threshold study, “Re-evaluating Acceptable Risk of Death from Gene Therapy,” has been published in the European Journal of Medical Genetics. This work addresses a critical question: how should risk and benefit be assessed and balanced in potentially life-changing gene therapies for conditions like Duchenne muscular dystrophy?
In developing and considering therapeutic options, individuals living with Duchenne, families, researchers, clinicians, and regulators must weigh how much risk is acceptable in hopes of achieving meaningful benefit. But the risk tolerance and value of a given therapeutic intervention may differ between all of those groups. This work aimed to provide quantitative data about what level of risk—including ‘maximum acceptable risk’ (MAR) of death—patients or their caregivers might accept in exchange for a hypothetical gene therapy that would slow disease progression. Capturing the risk tolerance of patients and caregivers in rigorous data-driven studies is key to ensuring the patient voice is incorporated into clinical and regulatory decisions.
Study Takeaways
Study participants were asked to consider non-curative gene therapy options and to indicate the highest risk of death they would accept in exchange for benefit. The results showed that many respondents reported relatively high tolerance for risk, especially when the therapy could slow or halt disease progression. A similar study was conducted in 2018 prior to the first systemic administration of a gene therapy for Duchenne and when death associated with gene therapy was hypothetical, with similar outcomes for patient and caregiver risk tolerance.
Additionally, MAR was lowest during the newborn time period, and increased with disease progression. The highest MAR was at 5.4% in the last year of being able to lift one’s hand to their mouth (indicating ability to meaningfully use one’s arms).
“Assessing risk in the context of functional stages allows researchers to align therapies with the specific needs of patients as their abilities change over time,” said Eric Camino, PhD, PPMD’s VP of Research and Clinical Innovation. “It’s a crucial tool for developing therapies that are meaningful, practical, and safe.”
Why This Matters for the Duchenne Community
Each day presents the Duchenne community with difficult trade-offs. While gene therapies offer hopeful possibilities, they also carry uncertainties—especially with new technology. With this study, data now exists to help regulatory agencies, clinicians, researchers, and the community think about safety thresholds in a thoughtful, patient-centered way.
“Understanding how families think about risk helps bring humanity into the science,” notes Brian Denger, PPMD’s Community Engagement Manager and Duchenne parent. “It ensures that when we talk about safety and benefit, we’re not just talking about statistics—we’re talking about our children, our families, and what we’re willing to face for the chance to improve their quality of life.”
In May 2023, PPMD submitted the U.S. data from this study to the FDA as part of the Advisory Committee review for ELEVIDYS, ensuring that the real voices and perspectives of families informed the agency’s understanding of acceptable risk. This contribution demonstrates how community-generated evidence can play a vital role in shaping how regulators evaluate the balance of safety and benefit in emerging therapies.
“PPMD’s goal has always been to make sure that science and its regulation don’t happen in isolation from the people they’re meant to serve,” PPMD’s CEO Katherine Beaverson, MS, said. “By contributing to this research and sharing it with the FDA, we’re helping build a framework where patient priorities and real-world perspectives guide how therapies are developed, evaluated, and ultimately approved.”
For the Duchenne and Becker community, this is more than a theoretical discussion: it’s central to how future therapies will be evaluated and approved. By contributing to this research, PPMD helps ensure that the voices of the Duchenne community are part of the scientific and regulatory decisions that will affect us all. This is essential to making sure that future therapies are developed with both innovation and compassion—aiming for maximum benefit and minimal harm.
PPMD is proud to have worked collaboratively with Duchenne UK, who led the project with support from industry partners, in the development, data collection, and publishing of these results. Thank you to all the families who participated in this important study and to our sponsors for their support of this key research.
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