Sarepta Therapeutics’ DMD gene therapy shows early success

Sarepta Therapeutics has revealed some early promising data for its Duchenne muscular dystrophy (DMD), although the company also reported serious adverse events associated with the treatment.

The 12-week results come from the first 11 participants enrolled in Sarepta’s Study SRP-9001-103 or ENDEAVOR study, which is being conducted in partnership with Swiss pharma company Roche.

The study, which has so far enrolled 20 participants with DMD between the ages of four to seven, is aiming to determine the change from baseline in the quantity of micro-dystrophin protein expression at 12 weeks following administration with the gene therapy, SRP-9001.

SRP-9001 is an investigational gene therapy designed to deliver the micro-dystrophin-encoding gene to muscle tissue to boost production of the micro-dystrophin protein.

DMD is caused by a change or mutation in the gene that encodes instructions for dystrophin, meaning that people with the condition are unable to adequately make the micro-dystrophin protein on their own.

Over time, this causes progressive loss of muscle strength, with most patients requiring full-time use of a wheelchair by their early teens. Patients typically go on to experience increasing difficulty in breathing and cardiac dysfunction, which is usually fatal.

Results from the first clinical study of the DMD gene therapy – SRP-001 – found that the treatment demonstrated robust expression of micro-dystrophin, with mean micro-dystrophin expression of 55.4% of normal.

“This data shows strong transduction of the micro-dystrophin gene, resulting in robust expression of the properly localised micro-dystrophin protein, and did so with no new or unexpected safety signals,” said Doug Ingram, president and chief executive officer, Sarepta.

“In addition to characterising and differentiating SRP-9001, these results confirm the extraordinary work done over the last two and a half years to build an at-scale gene therapy manufacturing process and corresponding analytics sufficient to meet the needs of the Duchenne population with what we believe will be a potentially life-changing therapy. Armed with this data, we will seek a meeting with the FDA with the goal of rapidly starting our registrational study,” he added.

Although Sarepta did not identify any new safety signals from this study, the company did note that two patients experienced serious adverse events – however, these were ‘fully resolved’.

One of the patients experienced elevated levels of transaminases, an enzyme found in the liver, while the second patient had nausea and vomiting.

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