Sarepta shares slide as DMD treatment woes pile up
Louise Rodino-Klapac, Sarepta's president of R&D.
Shares in Sarepta Therapeutics lost nearly 40% of their value after the company said a trial designed to confirm the efficacy of two already-marketed drugs for Duchenne muscular dystrophy failed, raising the risk they could be pulled from the market.
The ESSENCE trial was intended to prove the efficacy of Vyondys 53 (golodirsen) and Amondys 45 (casimersen), which received accelerated approval from the FDA in 2019 and 2021, respectively, for DMD amenable to treatment with exon 53 and exon 45 skipping therapies.
Sarepta said that the trial did not achieve statistical significance on the primary endpoint for both drugs, but pointed to "positive and encouraging trends favouring therapy." It suggested that the study had been compromised by the COVID-19 pandemic and – if data from that period is excluded – there was a "meaningful treatment effect."
It is just the latest piece of negative news for Sarepta's DMD business, coming after it paused distribution of its gene therapy Elevidys (delandistrogene moxeparvovec) in the summer on liver toxicity concerns.
In its third-quarter results update, Sarepta said that sales of Elevidys were almost $50 million less than it would have expected as a result, with another $9 million hit from reduced shipments of Elevidys of ex-US commercial partner Roche. Total revenues were $399 million, down from $467 million in the same period of 2024, with Elevidys contributing $132 million and the remainder coming from its exon-skipping therapies for DMD.
In a statement, Sarepta said that it intends to seek a meeting with the FDA to discuss using the data to convert the accelerated approvals to full licenses based on clinical and real-world data.
"While the ESSENCE study did not meet statistical significance on its primary endpoint, we believe the results demonstrated a clear treatment effect, showing clinically meaningful functional outcomes for people with Duchenne who have mutations amenable to skipping exons 45 or 53," said Louise Rodino-Klapac, Sarepta's R&D chief.
"These topline findings reinforce the potential impact of these therapies to slow muscle weakness and other symptoms," she added.
Sarepta also said that it expects discussions with the FDA over changes to Elevidys' label to be finalised shortly, likely with an outcome that will see the addition of a boxed warning for liver toxicity and a restriction on its use to exclude non-ambulatory patients.
