FDA pauses PTC's phase 2 Huntington's trial despite green light from regulators abroad

The FDA has pumped the brakes on PTC Therapeutics’ Huntington's disease trial in the U.S. even as studies kick into gear in other countries.

The agency has requested additional data before it will allow the phase 2 study of PTC518 to proceed, the biotech revealed in an Oct. 18 release. PTC has therefore paused enrollment in the U.S. while it holds discussions with the regulator.

The New Jersey-based biotech pointed out that there have been no adverse events in any country tied to PTC518, its small-molecule splicing modifier designed to trigger a reduction in HTT protein levels.

The company didn’t give any further details on the FDA’s reasoning in the release, although RBC Capital Markets analyst Brian Abrahams, M.D., speculated in a note that the “modest setback” may be the result of moving patients from the initial 12-week portion of the trial to an additional nine-month treatment period. If that’s the case, the FDA’s caution may be a result of toxicity issues noted with other HTT-lowering agents, Abrahams said.

Meanwhile there is also a chance that the pause could be due to “a concerning preclinical signal,” and the fact that regulators outside the U.S. haven’t made similar moves “may suggest this is not necessarily a showstopper,” the analyst added.

Elsewhere, PTC has received approval in Australia and several European countries to conduct the combined 12-month PIVOT-HD trial, which will assess 5-mg and 10-mg doses as well as a potential third dose. The company hopes to share data from the initial 12-week segment in the first half of 2023.

Huntington’s is a notoriously tricky therapeutic area littered with clinical setbacks, including three patients hospitalized in a recent trial of uniQure’s candidate. Annexon also had its work cut out this year proving to investors that the dropout rate for its phase 2 trial had stabilized.