Sarepta Therapeutics has successfully defused concerns about a FDA clinical hold on one of its Duchenne muscular dystrophy (DMD) clinical trials. After initially plunging, the biotech’s share price stabilized when it reassured investors it could satisfy the regulator’s requests “in the next few days” and convinced analysts of the likelihood of a speedy resolution.
After markets closed Thursday, Sarepta disclosed a FDA clinical hold on a study of SRP-5051, a successor to Exondys 51 that is designed to increase tissue penetration and therefore efficacy. The FDA put part B of the phase 2 MOMENTUM clinical trial on hold after learning of a serious adverse event. The participant suffered low magnesium, known medically as hypomagnesemia. Sarepta CEO Doug Ingram expects to get the trial back on track soon.
“We are confident that we can provide clarifying information to satisfy the FDA’s requests in the next few days and to resume dosing in the U.S. very expeditiously,” Ingram said on a call with investors to discuss the hold. “The study remains ongoing outside of the United States and we remain on track to complete dosing in the second half of this year as previously guided.”
The case occurred eight days after the patient was randomized to the high-dose cohort. The patient had grade 3 hypomagnesemia, grade 4 potassium deficiency, muscular cramps and mild to moderate tingling of the extremities. Without hospitalizing the patient, the physicians administered an intravenous bolus of magnesium and sent them home on increased magnesium and potassium supplementation. Levels of magnesium returned to normal after three days, and there is no evidence of complications.
Sarepta already knew about the risk of low magnesium levels. SRP-5051, also known as vesleteplirsen, may interfere with reabsorption of magnesium and subjects in the study take supplements to counter the risk. The biotech has successfully brought down the number of hypomagnesemia cases.
Around 20% of patients in earlier studies of SRP-5051 experienced grade 3 or 4 hypomagnesemia. After adopting a monitoring and management plan, Sarepta saw the number of cases fall in MOMENTUM part B. While part B has seen “a small number” of grade 2 cases, the event that sparked the clinical hold is the first grade 3 case. The FDA has asked for information on all the cases as part of the clinical hold.
Analysts are sanguine about the hold. The team at Mizuho called the hold “disappointing” but expect it to “likely get resolved in the near-term,” adding that it “is not a major setback for Sarepta in the grand scheme of things.” That position reflects a belief that SRP-5051 is relatively unimportant to Sarepta’s prospects because it will primarily cannibalize Exondys 51 sales. Similarly, the team at Evercore ISI said the hold “isn’t entirely surprising following the part A data and has no impact to our model.”
Even so, the Evercore analysts do see theoretical risks related to the clinical hold, arguing that it may lead to more patients ending up on the low, potentially less efficacious dose. Under changes proposed by the safety review committee, patients who experience grade 2 hypomagnesemia will be randomized to the low-dose arm. Sarepta expects both doses to be therapeutic based on its part A MOMENTUM data.
Shares in Sarepta initially fell around $9 to $63 after the biotech disclosed the clinical hold. However, the stock recovered as investors digested the news, bringing the share price back up above $70.