The CureDuchenne, Sarepta Therapeutics Partnership

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

In advance of the upcoming regulatory action deadline for Sarepta Therapeutics’ investigational gene therapy for the treatment of Duchenne muscular dystrophy (DMD), delandistrogene moxeparvovec (i.e. SRP-9001), the FDA has determined it will hold an advisory committee (AdComm) meeting. As of the publish date of this article, the AdComm date has not been scheduled, but it should take place before the PDUFA date of May 29, 2023. Sarepta’s SRP-9001 to treat DMD could receive accelerated approval from FDA. SRP-9001 is a gene therapy designed to deliver the microdystrophin-encoding gene into muscle tissue to prompt production of the microdystrophin protein. Patients with DMD have a mutation in the DMD gene and can’t make the protein on their own, leading to a progressive loss of muscle strength. CureDuchenne is a non-profit located in Newport Beach, CA, that focuses on supporting translational research with the aim of getting promising therapies out of the labs and into human trials as fast and as safely as possible and has partnered with Sarepta from its earliest stages. I caught up with Michael G. Kelly, Ph.D., Chief Scientific Officer at CureDuchenne to learn more about the organization and its partnership with Sarepta. Here’s what he had to say.

Explain CureDuchenne’s mission.

CureDuchenne is a global leader in funding research and development towards effective treatments, patient care, and innovation to improve and extend the lives of those with DMD. We focus on funding the most promising research programs aimed at treating and ultimately curing the disease, and increasing the knowledge, health, and wellbeing of the more than 300,000 individuals living with Duchenne around the world. We do this by informing parents, caregivers, and clinicians on best practices to improve outcomes, extend ambulation, and manage and care for individuals with DMD.  CureDuchenne Cares regularly holds 1:1 consultations with families, helping them understand the disease trajectory as well as the drug development/clinical trial landscape to help inform the decisions they face. A diagnosis of Duchenne can be overwhelming for many families, and the CureDuchenne Cares team holds workshops around the US (and abroad) to support families and patients throughout their journey.

Explain the organization’s venture philanthropy model and how the model has helped researchers, scientists, etc. develop therapies for DMD.

CureDuchenne Ventures was created to promote, fund, and de-risk innovative science to accelerate research programs for Duchenne into clinical trials and become approved therapies. We seek out emerging technologies and research that show the most promise for treating Duchenne, ensuring support for a diverse array of technologies that address gaps within the current clinical pipeline. We apply significant due diligence to de-risk projects and provide funding to obtain the critical “proof of concept” data needed to attract further investments. And our involvement doesn’t end there; we cultivate long-term strategic relationships with our drug development partners, providing deep domain expertise, insight and support as their programs advance. Finally, the returns made on these investments are leveraged and redeployed into new drug development opportunities, providing a successful self-perpetuating model that helps accelerate further novel approaches to treatment.

We’ve seen our due diligence and funding attract significant follow-on investments from Venture Capital firms and other companies. To date, 17 CureDuchenne-funded projects have advanced to human clinical trials, including the first FDA-approved therapy.

What does the upcoming FDA decision on Sarepta's gene therapy mean for the DMD patient community? 

Sarepta’s gene therapy, if approved, will mark a major milestone for Duchenne patients and their families. It will be the first gene therapy product approved to treat DMD – and it’s been many years in the making. The trial data released so far points to a significant clinical benefit in those patients treated, leading to improvements in measures such as the NSAA and timed function tests and a slowing of the progression of the disease. This has set high expectations within the DMD community.

But there is still much that we must do over the next few years to treat all patients, and to address issues that remain post-approval of this family of micro-dystrophin-based gene therapy products. For example, issues such as treating those patients (currently excluded from dosing) who have AAV-neutralizing antibodies from prior environmental AAV exposure, redosing patients following initial treatment, and of course the obvious need to deliver a larger dystrophin transcript and ultimately the full-length natural dystrophin gene to all muscle tissue.

What should we know going into the upcoming AdComm meeting?

The purpose of an Advisory Committee meeting is to provide the FDA with valuable input from outside experts to inform their decision. In addition to Sarepta, we can expect presentations from the public, advocacy groups (like CureDuchenne), physicians, patients, and other stakeholders. These people can share their perspective and experience on the severity of a condition and the state of current standards of care.

As of March 27, we do not have the date for the AdComm, but expect it to happen before the PDUFA date of May 29, 2023.

What will be covered at the AdComm meeting?

We don't know what will be covered at the AdComm - no agenda has been set

Will members of the CureDuchenne community be at the meeting to share their insight?

We are awaiting a date and details for this meeting, but CureDuchenne and our community is ready to participate in support of Sarepta’s BLA application, based upon the impact this gene-therapy approach will have on the Duchenne community.

The upcoming AdComm and subsequent decision by the FDA to approve the first gene-therapy product to treat DMD marks a defining moment for hundreds of Duchenne patients (along with their extended families) who have sacrificed, taken risks, and participated in these clinical trials. Its approval will provide hope to tens of thousands of others living with Duchenne that their lives will be improved because of their action and the actions of the Advisory Committee and the FDA.

Explain the partnership between CureDuchenne and Sarepta.

In 2010, CureDuchenne provided funding to AVI Biopharma (which later became Sarepta Therapeutics) at a critical time for the company, which allowed them to initiate their first clinical trial. This early funding was essential for them to move forward and become the company they are today, with three approved exon-skipping drugs for Duchenne and multiple clinical trials for Duchenne underway in both gene therapy and exon-skipping.

We continue to partner with Sarepta through our nationwide CureDuchenne Cares events to bring awareness of ongoing clinical trials and to share updates with families.