October 30, 2023
Dear U.S. Duchenne community,
In the past months we have received many inquiries about delandistrogene moxeparvovec’s evolving clinical development program and our plans to address the unmet need that remains. The interest mostly has been about the potential future availability of this therapy for a broader range of people living with Duchenne: across differing ages, stages, antibody status, or mutations. We recognize the urgency in each outreach. In this letter, we share recent news, as well as outline our ongoing and planned activities to best support the community’s therapeutic needs as quickly as science and regulatory requirements allow.
In June, the FDA approved delandistrogene moxeparvovec for children with Duchenne aged 4 through 5 years. What is Sarepta’s plan to pursue approval for additional ages and stages of disease?
- Today, we announced topline results from the EMBARK study (NCT05096221), a global, randomized, double-blind, placebo-controlled, Phase 3 clinical study of delandistrogene moxeparvovec. Topline results offer an early view of key safety and efficacy data from a study. Additional data and analyses will be released at a future medical conference.
- We believe the results support our plan to move swiftly to request expansion of the label by FDA to the fullest extent possible, as rapidly as possible.
- FDA has indicated, based on the totality of the evidence, openness to label expansion if supported by review of the data. Consideration of broad labeling is consistent with FDA authorities, guidance, and prior approvals inside and outside of Duchenne.
- Importantly, there will be time between today’s announcement of the topline EMBARK data and when any FDA labeling changes may occur. Recognizing the community’s urgency, we are working as quickly as possible to formally submit the new data to the FDA. Similarly, FDA has indicated its intent to proceed rapidly with consideration of the submission.
What studies are you doing to further understand the safety and efficacy of delandistrogene moxeparvovec in additional ages and stages of Duchenne beyond the currently FDA-approved indication and the EMBARK study?
- ENVISION (NCT05881408) is a global Phase 3 clinical study that aims to evaluate the safety and efficacy of delandistrogene moxeparvovec in non-ambulatory boys (of any age) and older ambulatory boys (aged 8-18 years). Currently, the study is fully enrolled in the US and the remainder of the study is planned to enroll outside the United States.
- Those who have been following the ENDEAVOR study (NCT04626674) understand that the study explores use of delandistrogene moxeparvovec in different populations of people living with Duchenne.
- In this open-label U.S.-based study, we have previously enrolled 5 cohorts that include people with Duchenne who are ambulatory, older ambulatory, non-ambulatory, age 3, or have mutations in the 1-17 range.
- We recently added two new cohorts in ENDEAVOR to explore the use of delandistrogene moxeparvovec in 2-year-olds and another cohort for those whose lung function is more affected than previously studied groups.
- Please note that these cohorts are small and clinicians who are already involved in the ENDEAVOR study may be able to fully recruit for these cohorts from within their existing clinic populations (this is called “recruiting by invitation”).
I know that some people with Duchenne have pre-existing antibodies to delandistrogene moxeparvovec which means they currently cannot receive the therapy. What studies are planned to evaluate how to overcome pre-existing antibodies?
- In the coming months, we anticipate starting two different studies to explore two different mechanisms for reducing pre-existing antibodies to AAVrh74, the vector used in delandistrogene moxeparvovec.
- We plan to initiate a U.S. study of apheresis plus delandistrogene moxeparvovec. In this study we will evaluate if removing blood plasma from people living with Duchenne, filtering out antibodies, and returning the filtered blood to the individual, will remove enough antibodies so that delandistrogene moxeparvovec may be administered to participants in the study.
- We plan to initiate a study in Europe which will evaluate if imlifidase, a Hansa Biopharma therapy for use in transplant medicine, breaks down antibodies enough so that delandistrogene moxeparvovec may be administered to study participants.
- Both studies are small, and investigators may be able to fully enroll participants from within their existing clinic populations (recruiting by invitation).
Community members have also asked how we might safely expand eligibility for those who have deletions including exons 8 or 9, or if it may be feasible to one day receive a repeated dose of gene therapy. Our research and development teams at Sarepta, with our partner Roche, are dedicated to pushing the leading edge of science forward. We, and the wider scientific community, have much work to do to evaluate these questions and any potential future strategies.
The delandistrogene moxeparvovec program is in full motion at present. We have designed our clinical development program and regulatory approach so that our gene therapy may reach as many people living with Duchenne as possible, as quickly as possible. In the U.S., the only routes through which individuals with Duchenne may receive delandistrogene moxeparvovec are through Sarepta-sponsored clinical trials or through regulatory approval. This letter highlights key near-term studies and approaches we are undertaking as we work toward this goal. Additional studies are underway or will be planned to answer evolving questions in the field.
We and Roche, our worldwide partner for delandistrogene moxeparvovec, share our continued gratitude for the individuals and families for their ongoing participation in EMBARK and other clinical studies. Your contributions offer immeasurable value to the understanding of delandistrogene moxeparvovec, and also to the understanding of Duchenne.
Please share your questions with the Patient Affairs team if some arise by emailing [email protected]
The Patient Affairs Team