The share price of Sarepta has fallen sharply after a surprise FDA rejection of Vyondys 53, the company’s latest treatment for Duchenne Muscular Dystrophy (DMD) yesterday.
The share price fell 12% in after-hours trading in response to the FDA complete response letter (CRL), which raised concerns about a risk of infections related to the intravenous infusion port used to administer the therapy.
It also highlighted worries about kidney toxicity seen in preclinical studies – but Sarepta says the US regulator has placed so much emphasis on what it argues are insignificant data signals.
The rejection has come as a surprise to the company and analysts, and could be a major setback to its plans to consolidate its lead in the therapy area.
Vyondys 53 (golodirsen) follows Exondys 51, the first and currently only disease-modifying treatment approved in the US for the inherited muscle-wasting disease.
Sarepta gained approval for Exondys 51 three years ago amid controversy about its lack of robust efficacy data, but the drug is now established and creating a market for follow-on drugs.
Vyondys uses the same ‘exon skipping’ mechanism, but helps patients with the exon 51 mutation rather than on exon 53. These patients represent around 8% of the DMD population, while those with the exon 51 mutation account for around 13%.
The company has now requested an immediate meeting with the FDA to seek guidance on what its next steps should be.We are very surprised to have received the complete response letter this afternoon. Over the entire course of its review, the Agency did not raise any issues suggesting the non-approvability of golodirsen, including the issues that formed the basis of the complete response letter,” said Doug Ingram, president and chief executive officer, Sarepta.
“We will work with the division to address the issues raised in the letter and, to the fullest extent possible, find an expeditious pathway forward for the approval of golodirsen. We know that the patient community is waiting.”
The company has a third therapy, called casimersen, which it is planning to file shortly with the FDA. Using a similar mechanism, this drug skips exon 45, and analysts predict that if Sarepta can achieve approval for all three drugs, it could cover about 30% of DMD patients.
Analysts at Leerink estimate the three drugs could reach sales of $1.7bn by 2024, a figure boosted by the fact that the company is currently well ahead of potential rivals in DMD.
The question of clinical efficacy, which proved so controversial with Exondys has not been raised by the FDA in its CRL.
Sarepta submitted efficacy data for Vyondys to the FDA from an open-label trial of 25 boys with DMD, which showed signs of the drug producing exon 53 skipping. The key endpoint was the effect on mean dystrophin protein, which increased to 1.019% of normal, compared with 0.095% at baseline, after 48 weeks of treatment. This represents a 10.7-fold increase, but critics argue there isn’t evidence that this change is enough to slow the progress of the disease meaningfully.
Sarepta has an ongoing randomised double-blind, placebo-controlled study, ESSENCE, which is assessing the efficacy and safety of golodirsen and casimersen, which should provide more robust data on whether these new agents work or not.
The company is also investing in gene therapies for DMD and a range of other rare diseases as well as multiple sclerosis