Wave Life Sciences has joined the biopharma sector’s gold rush to treat DMD, a genetic disorder that causes progressive musculoskeletal disability in boys.
So far, a single targeted treatment has been approved, Sarepta’s Exondys 51 (eteplirsen), which treats the 13% of patients with a mutation in exon 51 of the DMD gene that causes a non-functional version of the muscle-building protein dystrophin to be produced. By preventing duplication of the error, Exondys 51 purports to spur production of a shortened but effective version of dystrophin.
Wave’s suvodirsen aimed to do the same thing by “skipping” exon 51, and has been in a Phase 1 trial that aimed to identify a tolerable effective dose. Investigators enrolled 36 patients, with the hope of increasing form 0.5 mg/kg of body weight up to 10 mg/kg.
The patient treated at the higher dose suffered adverse events which were deemed “nonserious but severe” by trial investigators. His symptoms resolved after treatment with acetaminophen and hydrocortisone.
Another patient was then dosed at 7 mg/kg, but suffered fever that was again eased with acetaminophen. Trial investigators concluded the 5 mg/kg dose was a tolerable dose.
Stifel analyst Paul Matteis downgraded Wave shares from “buy” to “hold”, commenting in a client note that such adverse events “after a single dose are disconcerting, and we are unsure if they’re able to dose high enough for efficacy.”
Shares fell 28% Tuesday following the news and the downgrade. The safety setback came a week after Wave disappointed investors by also announcing a delay to its Huntington’s disease program.
Even worse for Wave and all other rivals for Sarepta’s DMD crown is that the evidence of functional improvement with Exondys 51 — controversially lacking when it was approved in 2016 — at long last may be emerging.
A statistical analysis of patients in several Exondys 51 trials published as a poster at MDA indicated that patients taking Exondys 51 have seen a significant delay in their loss of ambulation, and are more likely to be able to complete a six-minute walk test, than patients receiving the standard of care four years after initiating treatment.
Sarepta’s lead is not scaring away rivals, however. Companies like Audentes Therapeutics and Solid Biosciences are testing exon-skipping and gene therapy candidates to take on Exondys 51 and Sarepta’s highly anticipated SRP-9001 Micro-Dystrophin.
