Sarepta Faces Setback in DMD Therapies
Sarepta Therapeutics has been receiving challenges one after another. The company announced that its exon-skipping therapies, Vyondys 53 and Amondys 45, did not significantly improve motor function in patients with Duchenne muscular dystrophy. However, Sarepta will pursue the treatments for full FDA approval, notifying its investors of its intentions during its third-quarter earnings call.
William Blair analysts indicated that the future of the drugs is marred despite the optimism by Sarepta on the results of the trials. The authors consider the failure of the ESSENCE trial to achieve its main objective as bad news.
Although the management is confident that Vyondys 53 and Amondys 45 will not be deprived of marketing authorization due to this, we are less optimistic, and we believe the stock response (down 37 percent after hours) indicates that investors also have their concerns regarding the future of the two products.
Understanding the Therapies and Trial
Both Vyondys and Amondys are antisense oligonucleotides that target the inhibition of a specific exon in the pre-mRNA of the dystrophin gene, and as a result lead to a shorter but otherwise functional protein. Vyondys 53 is an exon 53 skipper, approved in 2019, and Amondys 45 is an exon 45 skipper, approved in 2021, both under the accelerated pathway of the FDA.
In 2016, Sarepta initiated the Phase III trial ESSENCE to use it as a confirmatory study. ESSENCE pitted Vyondys and Amondys against a placebo in close to 230 patients, studying the effect of these drugs on the timed motor performance. Findings on Monday demonstrated that there was a 0.05-step/second improvement in the same outcome in patients who received antisense therapy—a statistically insignificant result.
Company’s Response and Future Plans
Sarepta attributed the miss to COVID-19, which the biotech asserted had affected the study subjects and their results. Sarepta, when eliminating the data on patients who underwent testing during the pandemic, observed a 30% rate of decrease in the progression of the disease over the 2 years. This also did not significantly differ, but the biotech considered it a clinically significant difference.
Sarepta, even after failing the ESSENCE trial, will seek complete approval of Vyondys and Amondys based on what the company termed as “encouraging trends” in the trial. The biotech also cited substantial real-world support of the clinical value of both drugs and their positive safety profile. “Vyondys and Amondys are used in patients of all age groups since their accelerated approvals with a proven survival and functional benefit,” Sarepta said on Monday.
The failure of ESSENCE builds on a challenging year for Sarepta, also characterized by three deaths of its patients treated with gene therapies, two linked to the FDA-approved DMD drug Elevidys, and one to a preclinical candidate in limb-girdle muscular dystrophy. Contrary to these deaths, the FDA withdrew the platform technology designation that it had given Sarepta to the firm in June.
