Fresh safety, tolerability data snapshot from early-stage study of Wave’s DMD drug spooks investors

Wave Life Sciences irked investors with the latest snapshot of safety data on its experimental Duchenne muscular dystrophy (DMD) drug on Tuesday, causing Wall Street to question whether the results from the early-stage study foreshadowed trouble ahead.

The experimental drug, suvodirsen, is being tested in the same DMD population that Sarepta’s $SRPT pioneering Exondys 51 is approved to treat — boys who are amenable to exon 51 skipping. In the Phase I study, 36 patients received a dose of 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 7 mg/kg or 10 mg/kg of suvodirsen (n=26) or placebo (n=10) in five ascending dose cohorts and were followed for 85 days.

Results from the first four cohorts (0.5 mg/kg – 5 mg/kg) showed that 16/24 patients who received suvodirsen and 8/10 patients who received the placebo experienced one or more adverse events of mild-to-moderate intensity including pyrexia, headache, vomiting and tachycardia.

On Tuesday, data from the fifth cohort — 2 patients administered with the 7 mg/kg or 10 mg/kg dose of suvodirsen — were unveiled. Similar side effects were reported as those observed at lower doses, but were more severe in intensity, Wave said. The Cambridge, Massachusetts-based company’s shares $WVE tumbled more than 28% to close up at $24.47 on Tuesday, as investors took issue with the drug’s tolerability profile.

Paul Matteis

These “appear to be dose-limiting immunotoxicities…it’s unclear if this profile will get better or worse upon repeat dosing,” Stifel’s Paul Matteis wrote in a note.

For the pivotal Phase II/III trial — expected to commence in July 2019 — Wave has chosen to evaluate 3.0 or 4.5 mg/kg of suvodirsen once weekly for 48 weeks in 150 boys. However, an improvement in manufacturing has allowed the company to arm the 4.5 mg/kg dose with the same quantity of active ingredient as the 5 mg/kg used in the Phase I study.

“The fact that FDA has signed off on this trial is a positive, but it’s hard for us to have conviction that these dose levels will be sufficient,” Matteis added.

Another possible sticking point is the comparison of suvodirsen with BioMarin’s $BMRN rejected DMD drug, drisapersen, SVB Leerink’s Mani Foroohar wrote in a note.

Mani Foroohar

“(I)nvestors seem to see negative read-throughs for the potential efficacy of suvodirsen at 5 mg/kg, given that drisapersen was dosed at 6 mg/kg in clinical trials, we believe that due to differences in chemistry between the compounds, comparison of doses between drugs is not an appropriate proxy of potential efficacy.”

Foroohar said he was maintaining a 30% probability of success on the suvodirsen program.

“We believe we have selected the optimal doses to bring forward in our ongoing open-label extension study and planned Phase 2/3 trial. We look forward to sharing the dystrophin results from muscle biopsies taken from the open-label extension study in the second half of this year,” Wave chief Paul Bolno said in an emailed statement.

The best place to read Endpoints News? In your inbox.

Comprehensive daily news report for those who discover, develop, and market drugs. Join 47,800+ biopharma pros who read Endpoints News by email every day.

Free Subscription

Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

Visit Endpoints Careers ->