Sarepta nevertheless plans to push for full FDA approval of Vyondys 53 and Amondys 45 based on what it said are “encouraging trends” in efficacy.
The challenges just keep coming for Sarepta Therapeutics. The company reported that its exon-skipping therapies Vyondys 53 and Amondys 45 failed to significantly improve motor function in patients with Duchenne muscular dystrophy. Nevertheless, Sarepta will seek full FDA approval of the treatments, announcing the plans during its third-quarter earnings call Monday.
The biotech was trading at $15.60 in pre-market trading on Tuesday, representing a 36% drop from Monday’s closing share price of $24.45.
In a note to investors Tuesday morning, William Blair analysts said that, despite Sarepta’s optimism, the drugs’ trial results cloud their future. “We view the ESSENCE trial’s failure to meet its primary endpoint as a negative development,” they wrote.
“Despite management’s confidence that Vyondys 53 and Amondys 45 will not lose marketing authorization as a result, we are more skeptical, and think the stock’s reaction (down 37% after hours) suggests investors are also concerned about the future of these two products.”
Vyondys and Amondys are both antisense oligonucleotides that work by blocking off a particular exon in the pre-mRNA of the dystrophin gene, in turn resulting in a shorter but otherwise functional form of the protein. Vyondys 53 targets exon 53 and was approved in 2019, while Amondys 45 cuts out exon 45 and was given the go-ahead in 2021, both under the FDA’s accelerated pathway.
In 2016, Sarepta launched the Phase III ESSENCE trial to serve as a confirmatory study. ESSENCE compared Vyondys and Amondys against placebo in nearly 230 patients, looking at the effect these drugs have on timed motor function. Results presented on Monday showed that patients on antisense therapy saw a 0.05-step/second improvement in this outcome—an effect that fell short of statistical significance.
Sarepta blamed the miss on COVID-19, which the biotech claimed “impacted study participants and outcomes.” When excluding data from patients who were tested during the pandemic, Sarepta found a 30% reduction in disease progression over 2 years. This effect was also not statistically significant, but the biotech deemed it to be a “clinically meaningful change.”
Despite failing the ESSENCE trial, Sarepta will still file for full approval of Vyondys and Amondys, citing what it calls “encouraging trends” in the study. The biotech also referred to “substantial real-world evidence” supporting the clinical value of both drugs, as well as their “positive safety profile.” Since their accelerated approvals, Vyondys and Amondys have been administered to more than 1,800 patients of all ages, demonstrating survival and functional benefits, Sarepta said on Monday.
ESSENCE’s failure continues what has been a difficult year for Sarepta, marked by three patient deaths associated with its gene therapies—two linked to the FDA-approved DMD treatment Elevidys and one to an investigational asset for limb-girdle muscular dystrophy. In line with these fatalities, the FDA revoked Sarepta’s platform technology designation, which it had awarded to the company in June.
Sarepta also reported its Q3 performance on Monday, recording a 15% year-on-year decline in total revenue to $399.4 million. The decrease was attributed to a nearly $50-million hit to sales of Elevidys following the biotech’s decision to voluntarily but temporarily suspend shipments to non-ambulatory patients. Sarepta did not report Q3 sales for Vyondys or Amondys.
