A drug candidate from PepGen showed signs it could be more potent than other therapies in testing for a rare muscle disorder, sending the biotechnology company’s shares soaring more than 90% on Tuesday.
PepGen has been testing its experimental oligonucleotide drug, PGN-EDODM1, in a Phase 2 trial in people with the muscle-wasting condition myotonic dystrophy type 1. In that disease, known for short as “DM1,” a genetic mutation leads to the creation of faulty RNA that clumps together in cells. The result is extensive “mis-splicing,” or jumbled protein instructions, and progressively compromised muscle function.
PepGen’s drug is designed to fix the problem by getting into cells and breaking up these RNA tangles. After 13 weeks of follow-up in the Phase 2 study, 4 monthly doses of PGN-EDODM1 helped repair, on average, 46.5% of the “splicing” errors that occurred in six treated patients. For four of those patients, that number exceeded 50%. PepGen claimed in a statement Tuesday that those figures represent the “highest level of splicing correction ever” in a study testing multiple doses of a DM1 drug.
The company also said that these findings were accompanied by improvements on multiple evaluations of mobility and muscle strength, such as a test showing how quickly a person’s hand muscles relax after a forceful contraction.
All treatment-related side effects were judged as “mild to moderate” by study investigators. Nausea was the most common adverse event. Treatment was associated with a temporary increase in protein in the urine after the first dose. Importantly, there was no evidence of cumulative kidney damage over the 16-week observation period, a worry with systemically administered RNA-based medicines like PepGen’s.
DM1 is characterized by a gradual weakening and shrinking of muscles as well as “myotonia,” the inability of those muscles to relax. It can also impact multiple other parts of the body, including the heart, lungs, eyes and stomach. The disease is estimated to affect some 110,000 people in the U.S. and Europe, according to PepGen.
No curative therapies for DM1 exist. PepGen, however, is one of several biotechs developing an RNA-based therapy designed to alter the disease’s trajectory. One, which Novartis acquired in a multibillion-dollar deal, recently failed a pivotal study. Another from Dyne Therapeutics is in advanced testing, while Sarepta Therapeutics has a third in an early-stage trial.
To some Wall Street analysts, the results PepGen disclosed Tuesday suggest its treatment could have the biggest upside in the group. The average “splicing correction” figure PepGen reported was higher than what’s been observed in testing of Novartis’ candidate del-desiran and Dyne's z-basivarsen, wrote Leerink Partners analyst Joseph Schwartz.
While “cross-trial comparisons remain imperfect,” Schwartz wrote, “the magnitude and consistency” of the results “support clear best-in-class potential.”
The findings represent a “best-case scenario,” added Oppenheimer analyst Kostas Biliouris, in a separate note.
PepGen is testing a higher dose in the trial and expects to report those results in the first half of next year. The study involves sites in several countries, but dosing hasn’t occurred in the U.S. due to a partial hold from U.S. regulators last year. That hold was related to findings the Food and Drug Administration flagged in animal studies.
The situation in the U.S. still leaves PepGen with some “underlying risk,” wrote Stifel analyst Paul Matteis. But “patient safety has looked favorable,” which should “help forge the path to clearing this.”
