PepGen's PGN-EDODM1 corrects 46.5% of splicing errors in six DM1 patients in Phase 2

PepGen reported early Phase 2 results for its experimental oligonucleotide drug PGN-EDODM1 in myotonic dystrophy type 1 (DM1), according to biopharmadive.com. The company's shares rose more than 90% on Tuesday after the disclosure. biopharmadive.combiopharmadive.combiopharmadive.comOpen source ↗

In DM1, a genetic mutation produces faulty RNA that clumps inside cells. This causes extensive mis-splicing, meaning jumbled protein instructions, and progressive loss of muscle function. PepGen's drug is designed to enter cells and break up these RNA tangles.

Splicing correction and clinical measures

After 13 weeks of follow-up, four monthly doses of PGN-EDODM1 repaired on average 46.5% of splicing errors in six treated patients. In four of them the figure exceeded 50%. PepGen said in a statement that this is the highest level of splicing correction ever seen in a multiple-dose DM1 study.

The company also reported improvements on several assessments of mobility and muscle strength, including a test of how quickly hand muscles relax after a forceful contraction. biopharmadive.combiopharmadive.combiopharmadive.comOpen source ↗

Safety and next steps

Study investigators rated all treatment-related side effects as mild to moderate. Nausea was the most common. A temporary rise in urinary protein followed the first dose. Over the 16-week observation period there was no evidence of cumulative kidney damage, a concern with systemically administered RNA-based medicines.

PepGen is testing a higher dose in the same trial and expects results in the first half of next year. The study has sites in several countries, but no dosing has taken place in the U.S. because of a partial hold from U.S. regulators last year. The hold relates to findings in animal studies flagged by the Food and Drug Administration.

DM1 causes gradual muscle weakening and wasting and myotonia, the inability of muscles to relax. It can also affect the heart, lungs, eyes and stomach. PepGen estimates it affects some 110,000 people in the U.S. and Europe. No curative therapies exist. biopharmadive.combiopharmadive.combiopharmadive.comOpen source ↗

Other RNA-based candidates are in development. A Novartis drug recently failed a pivotal study, a Dyne Therapeutics candidate is in advanced testing, and Sarepta Therapeutics has one in an early-stage trial. Leerink Partners analyst Joseph Schwartz wrote that PepGen's average splicing correction was higher than that observed with Novartis' del-desiran and Dyne's z-basivarsen, while noting that cross-trial comparisons remain imperfect.