PepGen announced on Mar. 31 that its lead drug candidate, PGN-EDODM1, showed mixed results in a mid-stage clinical trial for myotonic dystrophy type 1 (DM1), leading to a sharp drop in the company's share price. The company reported that its stock fell by 59% after the opening bell on Tuesday following the data release.
The news is significant for patients with DM1, a rare muscle-wasting disease caused by mutations in the DMPK gene. There are currently limited treatment options for this condition.
In the FREEDOM2 study's multiple ascending dose cohort, six patients receiving 5 mg/kg of PGN-EDODM1 had an average splicing correction of 7.3%, compared to 6.8% in two placebo patients, according to PepGen's announcement. The company said that if one outlier who experienced a significant worsening was excluded, the mean splicing correction improved to 22.9%. However, William Blair analysts said there was "minimal separation from placebo" and noted that this group also saw less improvement than those given a single ascending dose of PGN-EDODM1, which resulted in a 12.3% correction.
William Blair said "the splicing response rate is 50% at 5 mg/kg, which leaves room for improvement." PepGen also reported no meaningful improvements were observed in tests measuring walking or handgrip strength at this dose level.
The FREEDOM2 study included eight participants who received either PGN-EDODM1 or placebo every four weeks over twelve weeks. Key endpoints included safety and measures of functional outcomes such as hand-opening time and strength tests.
Other companies working on treatments for DM1 include Dyne Therapeutics and Avidity Biosciences—recently acquired by Novartis—as well as Sarepta Therapeutics with Arrowhead Pharmaceuticals on SRP-1003. William Blair said high variability has been seen across these studies due to small patient cohorts.
PepGen plans to report further data from higher-dose cohorts later this year.
