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Duchenne Research Update: October 2016

October 20, 2016

When I first joined the Duchenne community in 2009 at Children’s National Medical Center, I remember thinking that I was walking into a critical juncture in Duchenne history. There were three compounds in the clinic (drisapersen, ataluren, and eteplirsen aka Exondys 51) with more waiting in the wings to go into clinical trials, a drug development/regulatory landscape primed for rare disease drug development and, perhaps the most important piece, an engaged community of patients and families ready to roll up their sleeves and disrupt the process to create momentum.

As I sit to write this research roundup I realize it was not only a critical juncture, but the beginning of a new era in drug development. While we are not there yet, we are certainly in the midst of a dynamic, active research and development cycle with many opportunities being explored.

So much has happened in recent weeks in the Duchenne space that it is hard to keep up. While approvals and partnerships and regulatory actions have dominated the press, there is still a lot of pre-clinical and early stage clinical researchhappening behind the scenes, with great potential.

Here Is a Summary of What Is Going On:

First US Approval of a Duchenne Therapy

Sarepta Therapeutics received accelerated approval for Exondys 51 on September 19, 2016, with post regulatory commitments spelled out in the approval letter.

For those US patients amendable to an exon 51 skip you can contact SareptAssist for questions about access. If you are uncertain if you or your child is amenable to exon skipping, visit Decode Duchenne for free genetic testing and counseling.

Sarepta Collaborations

Sarepta recently announced two partnerships to broaden their portfolio of Duchenne therapeutic options.One partnership is with Catabasis who is pursuing an NF-kB inhibitor program (a protein that is activated in Duchenne and drives inflammation and fibrosis, muscle degeneration and suppresses muscle regeneration). The other is a licensing agreement with Summit Therapeutics, the developer of ezutromid, a utrophin modulator.Utrophin is a naturally occurring protein that is functionally and structurally similar to dystrophin.

Sarepta is expected to file an application for Exondys 51 in the European Union (EU) soon, but will have to resolve the patent issues with BioMarin to have the freedom to commercialize it there.

The Essence trial, for those amenable to exon 45 or 53 skips, has enrolled its first patients and is underway.

Under Review at FDA

Deflazacort, Marathon Pharmaceutical’s product, is under review at the FDA and a decision is expected sometime in February 2017. In the meantime, their expanded access program is underway. We look forward to more updates from Marathon in the coming weeks.

PTC Therapeutics holds a conditional approval for Translarna (ataluren) in the EU but received a refusal to file (RTF) letter in the US in February. Just this week, we learned that the FDA denied PTC first appeal of the RTF. As we understand it, this is a process and may involve additional appeals. PPMD will be meeting with PTC to better understand the communications that transpired between the agency and the company and how we as a community can support this process moving forward. In the meantime, a paper in PNAS was just published on the mechanism of action. They also recently published compelling pulmonary data in non-ambulatory patients.

Additionally, PPMD has been collecting patient experience data from those who have been on Translarna.Please take this survey if you have been in a clinical trial or are currently on drug.

PPMD continues to urge the FDA to give Translarna a full review and to conduct an advisory committee meeting.

Request by FDA for More Data

Santhera Pharmaceuticals filed for approval in the US for Raxone in non-glucocorticoid treated patients. The FDA said they wanted to see trial results of their Phase 3 in glucocorticoid treated patients before deciding. This could potentially delay an approval for 3 years.

Last year PPMD conducted a patient preference study around pulmonary outcomes in Duchenne. We found that patients and caregivers are willing to accept risk and burden in order to achieve pulmonary benefit., and that a drug like Santhera’s Idebenone presents a favorable choice for a potential treatment. PPMD shared these results with the FDA and we have also expressed the frustration of our community regarding the decision not to let Santhera file for accelerated approval.Read the report.

This Generation of Clinical Trials

The Duchenne community has worked hard to achieve such a rich pipeline of trials that are in the clinic, many of them supported by PPMD in earlier stages. We need to ensure trials are thorough and efficient, determining viability quickly, so that we don’t waste precious time and resources.

While this is not an exhaustive list, it does cover the candidates that are on the horizon. The first two, as mentioned, have partnerships with Sarepta, which will help them financially as they make their way through the riskier part of the development process.