FDA Places Hold on CONNECT2-EDO51, Sevasemten Meets End Point in Becker, Tolebrutinib Gets Breakthrough Therapy Designation

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a recent announcement, the FDA has placed a clinical hold on PepGen’s investigational new drug application for its phase 2 CONNECT2-EDO51 study, assessing PGN-EDO51 in patients with Duchenne muscular dystrophy (DMD), and will issue an official clinical hold letter within 30 days. The company noted that CONNECT2, a 25-week multinational, double-blind, placebo-controlled trial with multiple ascending doses, is currently open in the United Kingdom. Earlier this year in July, PepGen reported data from the first dose cohort (5 mg/kg) of its ongoing phase 2 CONNECT1-EDO51 study (NCT06079736) evaluating PGN-EDO51 in patients DMD amendable to an exon 51 skipping therapy. In the trial, PGN-EDO51 showed higher levels of exon skipping and had a comparable, or higher, change from baseline in total dystrophin production and muscle-adjusted dystrophin production compared with reports from prior studies with other oligonucleotide therapies at similar PMO dose levels in patients with DMD.

Edgewise Therapeutics has announced positive topline data from its phase 2 CANYON trial (NCT05291091), with results showing that investigational sevasemten, formerly known as EDG-5506, met its primary end point in change of creatine kinase (CK) among patients with Becker muscular dystrophy. Based on these encouraging findings, the company plans to work with the FDA and European Medicines Agency towards authorization filing strategies for the agent in Becker. The placebo-controlled, double-blind study featured 40 adults and 29 adolescents with Becker who were randomly assigned to either sevasemten or placebo for a 12-month treatment period, followed by a 4-week follow-up period. All told, over months 6 through 12, results revealed a 28% average difference in CK decrease among sevasemten-treated patients vs those on placebo (P = .02). According to Edgewise, this was the largest interventional trial to date in Becker and the first to achieve its primary end point.

According to a new announcement, the FDA has granted breakthrough therapy designation to Sanofi’s tolebrutinib, an investigational Bruton’s tyrosine kinase (BTK) inhibitor, for patients with non-relapsing secondary progressive multiple sclerosis (nrSPMS). The company noted that regulatory submissions for tolebrutinib are being finalized for the United States and prepared for Europe, with confirmation to follow once a submission has been accepted. This is designation was based on findings from the HERCULES phase 3 study (NCT04411641), which showed that treatment with tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP), the primary end point, by 31% compared with placebo (HR, 0.69; 95% CI, 0.55-0.88; P = .0026) in patients with nrSPMS.2,3 Additional results of the secondary end points revealed that the number of patients who experienced confirmed disability improvement increased by nearly 2-fold, 10%, for those treated with tolebrutinib compared with 5% those in the placebo group (HR, 1.88; 95% CI, 1.10-3.21; nominal P = .021).

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