FDA suspends US testing of Sarepta Duchenne drug over safety concerns

Dive Brief:

• The Food and Drug Administration has suspended testing of an experimental Duchenne muscular dystrophy drug from Sarepta Therapeutics to assess the risk of an adverse reaction that emerged in clinical testing.
• According to Sarepta, one patient treated with the drug, called SRP-5051 and meant to be a more potent version of Sarepta’s marketed medicine Exondys 51, experienced low magnesium levels that study investigators classified as serious. Sarepta said the FDA has requested information on that patient as well as a “small number of non-serious cases” to gauge whether the study’s safety guardrails are appropriate.
• Sarepta will respond to the FDA “within the next few days” and resume treating U.S. trial participants “expeditiously,” CEO Doug Ingram said on a conference call. The company expects to complete dosing later this year as planned, he added.

Dive Insight:

Sarepta is known for several RNA-based medicines that it’s brought to market for Duchenne muscular dystrophy, each of which help patients produce a shortened form of the muscle-protecting protein they would otherwise lack. But the drugs only produce small amounts of the protein, called dystrophin, and it’s still unclear how much they benefit patients.

Confirmatory stories meant to prove their efficacy are ongoing. In the meantime, Sarepta has been working on a newer technology it claims will produce more potent medicines. The company has six in development and SRP-5051, currently in Phase 2 testing, is the most advanced.

The drug showed promise in early testing, helping a small number of patients produce eight times more dystrophin than Exondys 51, chief scientific officer Louise Rodino-Klapac said on Thursday’s conference call.

But low magnesium levels, which can lead to heart damage and seizures, have emerged as a potential problem. Last year, the company reported cases in two of the first four patients treated in the ongoing Phase 2 trial. Sarepta amended its trial design to monitor for potential cases as a result. Executives said that oral magnesium supplements, which reversed the side effects in those two patients, might stop the condition from occurring in the future.

Even with those guardrails, laboratory tests showed another patient, who received the highest drug dose, experienced especially low magnesium and potassium levels, Rodino-Klapac said. The patient recovered after receiving intravenous magnesium and additional oral supplements.

Sarepta now thinks SRP-5051 “transiently interferes” with magnesium absorption in the kidneys, Rodino-Klapac said. The condition hasn’t worsened over time and the patients have recovered while still on treatment. The addition of magnesium supplements to the trial have helped reduce the frequency of events compared to earlier testing, she added.

Sarepta plans to add more stringent safety guidelines. According to Rodino-Klapac, the company will put patients who experience the side effect in a lower-dose group.

Though the study is now on hold in the U.S., it remains ongoing elsewhere. Sarepta also has trial sites in Europe and Canada. The company has already enrolled about half of the 60 patients in the trial, Rodino-Klapac said.

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