- Wave Life Sciences terminated clinical trials for its Duchenne muscular dystrophy drug after analyzing biopsies of patients in a Phase 1 trial and finding the drug did not increase production of the muscle-building protein dystrophin.
- Suvodirsen was being developed as a potential competitor to Sarepta Therapeutics' Exondys 51. Wave also suspended work for a second DMD drug, called WVE-N531, which would have treated a different subset of patients than suvodirsen. This would have been a rival to Sarepta's just approved Vyondys 53.
- Shares in the Cambridge, Massachusetts-based company plummeted 50% to about $18 apiece in early trading Monday. Analysts raised concerns that a similarly acting drug Wave has in development for Huntington's disease might also struggle to show effectiveness.
Wave's woes are another boon for Sarepta, as another potential rival is sidelined by clinical setbacks. Wave had planned to ask for Food and Drug Administration approval next year for suvodirsen if it had been able to show that it stimulated production of dystrophin in DMD patients amenable to exon 51 skipping, the same patient group served by Exondys.
Instead, the setback announced Monday clears the deck for Sarepta's portfolio of marketed products, with Vyondys — approved last week after a surprisingly quick turnaround by the FDA — no longer facing potential competition from WVE-N531, which had also entered human testing.
The path for Sarepta isn't completely clear, as Japan's NS Pharma has an application in for viltolarsen, which like Vyondys is intended for DMD patients amenable to exon 53 skipping.
With the cessation of clinical-stage testing for its exon-skipping DMD agents, Wave now is looking to preclinical assets that could target DMD patients with five other separate mutations.
Its analysis of suvodirsen patients in an extension of its Phase 1 trial included biopsies from 27 of 36 patients in two dosing groups, with 17 taken 22 weeks after initial treatment. A Phase 2/3 study called DYSTANCE 51 must now be wound up, with a final follow-up visit but no further dosing or biopsies.
Wave has one final catalyst for the year, results from the PRECISION-HD2 Phase 2 trial of WVE-120102 in Huntington's disease, a condition where new products might not face as much competition.
Stifel analyst Paul Matteis raised concern that the findings from the DMD trials suggest trouble for the Huntington's disease program, as both are oligonucleotides emerging from the same discovery technology.
All of the drugs in these two disorders "were supported by intriguing preclinical results, and DMD was the only one ... to show evidence of efficacy in a validated in vivo animal model. Thus, because this didn't translate at all into efficacy in patients, we are in turn lowering our probability of success for Huntington's as well," Matteis wrote in a Dec. 16 note to clients.