- Sarepta Therapeutics can resume testing an experimental gene therapy for Duchenne muscular dystrophy (DMD) now that regulators have lifted a clinical hold on the program, the company announced Monday.
- The hold began in late July after researchers found trace levels of DNA fragments in plasmids being used in a Phase 1/2a trial of the gene therapy, called microdystrophin. With the help of Nationwide Children’s Hospital, Sarepta submitted to the Food and Drug Administration plan to remedy the situation, which included an audit of the plasmid supplier and a pledge to use GMP-s plasmids moving forward.
- That plan appears to have alleviated the FDA's concerns. With the hold removed, Sarepta intends to start a registration trial for microdystrophin before the end of 2018.
All of Sarepta's revenue comes from a single product, Exondys 51 (eteplirsen). So far this year, the DMD drug has brought in roughly $70 million per quarter.
While that performance has helped stoke investor confidence in Sarepta — share value has nearly tripled since January — some headwinds remain. Just this week, the U.K.'s Committee for Medicinal Products for Human Use reiterated its recommendation that the National Health Services not cover eteplirsen because clinical data hasn't adequately illustrated the drug's risk-benefit profile.
From a business vantage, biotechs tend to de-risk themselves by expanding their portfolios. Sarepta's pipeline has a couple RNA-targeting therapies in late-stage testing, as well as a robust assortment of gene-therapy programs.
Microdystrophin is one of the more advanced in that latter category, and an integral part of how Sarepta sees itself tackling DMD.
"I am actually quite passionate about the idea that we should offer multiple modalities that can either be selected by patients based on preference or actually look at combinations to maximize the effect," Sarepta's Chief Medical Officer Gilmore O’Neill said during the company's second quarter earnings call.
"And so, from a strategic point of view, and a strategic intent, our goal and our objective would be to never exclude number of approaches," O'Neill added. "I think, the best way to look at it is the way we’re approaching Duchenne with [our phosphorodiamidate morpholino oligomer platform] and the gene therapy platform."
DMD, a rare muscular disorder, affects about 15 of every 100,000 males in the U.S. aged 5 to 24. Those patients didn't have any FDA-approved therapies until Exondys 51 about two years ago.
Exactly how beneficial Exondys 51 is has been a continual source of debate, however. Both critics and proponents of the drug agree that patient need would be better addressed with more marketed DMD therapies, yet setbacks in the clinic have stalled multiple candidates.
Massachusetts-based Solid Biosciences reported in March a clinical hold on its experimental DMD candidate, though that was resolved three months later. And in a more severe move, Pfizer recently decided not to further develop its DMD drug domagrozumab after it failed to show substantial benefits in a Phase 2 study.