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Rare Disease

Sarepta’s Duchenne gene therapy shows promise in small study

The early peek at data from a Phase I/II study excited families, physicians, and investors 

by Lisa M. Jarvis
June 20, 2018 | APPEARED IN VOLUME 96, ISSUE 26

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Good news

Sarepta's stock surged on news that its gene therapy helped three boys with Duchenne.

A small but encouraging study suggests a gene therapy developed by Cambridge, Mass.-based Sarepta Therapeutics could preserve muscles in boys with Duchenne muscular dystrophy. The early look at the therapy’s effectiveness was presented on June 19 at the biotech firm’s inaugural R&D day. Its stock price soared nearly 40%.

People with Duchenne muscular dystrophy, a rare disease that predominantly affects boys, have an error in a section of the gene for a protein called dystrophin, which cushions muscle cells from wear and tear. Without dystrophin, boys with Duchenne are often wheelchair-bound by their teens, and most die by their early 30s.

Over the past two decades, companies have tried many approaches to replacing or repairing the missing protein. In 2016, Sarepta gained approval for Exondys 51, an oligonucleotide that patches over a deleted stretch of the gene called exon 51.

But Exondys elicits dystrophin production of less than 1% of normal levels, and many experts are skeptical of its ability to prevent muscle deterioration.

In contrast, biopsies taken from the three boys treated with Sarepta’s gene therapy, which uses a truncated version of the gene that can be squeezed inside viral vectors, showed much higher protein levels—38% of normal using one test method and nearly 54% of normal using another.

Even though the results were limited to data from three patients collected within a few months of treatment, Duchenne experts were excited about the magnitude of the response. Jerry Mendell, a clinician at Nationwide Children’s Hospital, which is conducting the study, told attendees at the R&D day that the dataset “for me fulfills a lifetime of work.” Mendell noted that the Phase I/IIa trial will now be expanded to include 24 more kids, 12 of whom will initially be given a placebo.

Sarepta’s promising data raised expectations for two other companies—Solid Biosciences and Pfizer—developing gene therapies for Duchenne. But gene therapy’s win was treated by investors as a loss for other experimental drugs for Duchenne. Shares of Wave Life Sciences, which this spring initiated a Phase I study of WVE-210201, a chirally pure oligonucleotide for the Exon 51 mutation, were off by nearly 20%.

Although the stock market declared a victory, specialists who treat boys with Duchenne aren’t ready to yet.

“If this preliminary information is confirmed and holds up with additional patients, it is still possible that treated patients will develop some weaknesses because the level of dystrophin is not fully restored to normal and the microdystrophin is not identical to full-length dystrophin,” says Katherine Mathews, a neurologist who directs the Muscular Dystrophy Clinic at the University of Iowa’s Carver College of Medicine. “Therefore, gene therapy might be one of several drugs that might be used together to fully treat all aspects of the disease.”

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