FDA lifts hold on PTC Huntington’s disease trial

Dive Brief:

• PTC Therapeutics said Thursday it can resume a Phase 2 trial of its Huntington’s disease drug in the U.S., following the Food and Drug Administration’s review of data showing the pill reduced a mutant protein linked to the disorder.
• The drug, called PTC518, suppressed levels of huntingtin protein in both the blood and the cerebrospinal fluid by 43% in patients who took a once-daily 10 milligram dose over 12 months, PTC said. The company had previously disclosed data showing that dose reduced blood levels by around 30% through 12 weeks.
• Wall Street analysts said the data met company expectations for reducing mutant huntingtin levels by around 30% to 50% and should support advancing PTC518 into Phase 3 trials. PTC is competing with gene therapy company UniQure to gain approval of a drug to slow the progress of Huntington’s disease, which causes muscular problems, dementia and early death.

Dive Insight:

Resumption of U.S. clinical work with PTC518 could help PTC keep pace with UniQure, which bet its future on a Huntington’s disease gene therapy by selling off rights and a royalty stream to its hemophilia gene therapy Hemgenix. But the outlook for UniQure’s gene therapy isn’t straightforward, as patients who received its one-time therapy saw their mutant huntingtin levels rebound two years after receiving it.

PTC’s data is less mature than UniQure’s, but Wall Street analysts viewed the update as encouraging. In addition to the 10 milligram dose, the company also tested a 5 milligram dose. Study participants given that dose saw a reduction of mutant huntingtin by 22% in the blood and 21% in the cerebrospinal fluid, the latter of which is an indicator of a direct effect in the brain.

Patients receiving the pill also experienced slightly slower decline, as measured by a scale that assesses motor function. People who got the 10 milligram dose declined by 1.3 points on the scale, while those on the 5 milligram dose declined by 2 points. By comparison, patients given a placebo in the trial declined by almost 5 points. That compares with a 1-point improvement for people who got the UniQure gene therapy, analysts wrote.

However, PTC518 didn’t appear to have any impact on a blood marker that is indicative of nerve damage, which could prompt closer examination by analysts and regulators. Had the data on that marker, called neurofilament light protein, been better, the data might have been a “home run,” Cantor Fitzgerald analyst Kristen Kluska wrote in a note to clients.

Perhaps most importantly for the FDA, PTC reported no dose-limiting toxicities in the study. Adverse events were similar across treatment and placebo groups, the company said. 

Shares in PTC, which have risen this year on the news that the European Union won’t yet pull its muscular dystrophy drug Translarna, fell 5% in morning trading.