Sarepta sees muscle function gains with DMD gene therapy

DNA genomics precision medicine
Patients improved on measures such as their ability to climb stairs, get up from the floor or walk 100 meters. (PublicDomainPictures/Pixabay)

Sarepta’s case for its Duchenne muscular dystrophy (DMD) gene therapy is getting stronger, with early data now linking its effects on a critical protein with improved muscle function.

An earlier readout from the phase 1/2 trial in June from three patients treated with the gene therapy showed that it increased levels of microdystrophin—a truncated version of the dystrophin protein which is missing in DMD—and a fourth patient has now shown “robust” expression levels, says the company.

At the time, Sarepta said it was confident that the increases were enough to hold back the progressive muscle damage that characterizes the disease, but at the time it was relying purely on biomarkers such as serum creatine kinase (CK)—a sign of muscle damage—to gauge its effects. Now, it says the new data show functional improvements for all four patients on measures such as their ability to climb stairs, get up from the floor or walk 100 meters.

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The trial’s lead investigator, Jerry Mendell, M.D., of Nationwide Children’s Hospital, is cautious in his assessment of those improvements, saying: “while results suggest functional improvements across all measures significantly greater than natural history predictions, … this is a small, uncontrolled data set and these positive results must be reconfirmed in the larger, controlled registration trial.”

Nevertheless, it’s another baby step forward for the AAVrh74.MHCK7.micro-dystrophin program and the first time that a gene therapy has been shown to improve symptoms in DMD.

Encouragingly, the fourth patient also showed CK reductions alongside the increases in microdystrophin, with the group as a whole showing a 78% cut from baseline on that surrogate marker. Sarepta also presented new data showing that the microdystrophin was being expressed as intended mainly within the sarcolemma of skeletal muscles.

Shares in Sarepta wobbled a bit after the data was released, perhaps because of some variability in microdystrophin levels and particularly an unexpectedly high increase in patient four. It closed a little over 3% higher after investors sifted through the data, however, and added another 5% in after-hours trading.

The company’s share price has been climbing steadily for the last few months as the gene therapy program progressed, slipping back briefly after the FDA placed it on a clinical hold in July on a quality blip, only to remove it two months later.

Sarepta CEO Doug Ingram acknowledged that the data so far is preliminary, but said it has “strengthened our resolve to rapidly move to a confirming trial and, assuming successful, to bring this therapy to the Duchenne community around the world with a sense of urgency.”