PTC Therapeutics presented new biomarker data for a Huntington’s disease drug Thursday morning that it says demonstrates evidence of reducing the mutant huntingtin protein (mHTT) in patients’ systems, as well as a dose-dependent response in a small, 32-patient study.
After one year of taking a 10 mg dose of the drug, called PTC518, patients saw an average mHTT reduction in the bloodstream of 43%, compared to a 14% average increase in the placebo group. Patients taking a 5 mg dose also saw an average 22% reduction. Results were similar for mHTT levels in the cerebrospinal fluid, with reductions of 43% and 21%, respectively, for the 10 mg and 5 mg groups, compared to a 9% reduction in placebo patients.
PTC did not conduct a statistical analysis for these data, CEO Matthew Klein said, but noted the goal for the study had been a 30% to 50% “lowering” of mHTT. PTC also had the option to test a 20 mg dose, but Thursday’s results were good enough to not go beyond 10 mg, Klein said.
Matthew Klein“To be able to see this dose-dependent trend in a small number of patients at the 12-month timepoint is incredibly encouraging,” Klein said.
PTC shares $PTCT were down 6% in early Thursday morning trading.
The FDA also lifted a partial clinical hold on the Phase 2 study, the company said, after regulators originally paused US enrollment in October 2022. Thursday’s data come almost exactly one year after PTC presented 12-week data from the study.
With the new, one-year results now in hand, PTC will begin preparing for a Phase 3 study. Discussions with the FDA remain ongoing, Klein said, but there is a “strong argument” to use a primary endpoint looking at patients’ motor skills.
Klein said he was encouraged by the 12-month data because the observed protein-lowering effects stabilized after around six to nine months, suggesting the drug is still working at the one-year point. He also left open the possibility of going for an accelerated approval using blood or CSF huntingtin protein as a surrogate biomarker.
“We could certainly put that argument together, given the extensive literature now demonstrating that changes in the huntingtin protein could provide benefit to patients,” Klein said.