PTC Announces Positive Phase II Huntington’s Results, FDA Lifts Partial Hold

PTC Therapeutics revealed on Thursday that the FDA has lifted its partial clinical hold on PTC518, a promising candidate for Huntington’s disease treatment, following positive interim results from a Phase II trial. The PIVOT-HD study indicated that PTC518 effectively reduced mutant huntingtin (mHTT) protein levels in the blood and cerebrospinal fluid (CSF), a key marker for Huntington’s disease (HD).

The trial results demonstrated significant decreases in mHTT levels, with a 22% reduction in the blood at a 5mg dose and a 43% reduction at a 10mg dose. In the CSF, mHTT levels dropped by 21% and 43% for the 5mg and 10mg doses, respectively. Additionally, PTC518 showed promising effects on HD clinical assessments, including improvements on the Total Motor Score and the Composite Unified Huntington's Disease Rating Scale. These positive trends were accompanied by a favorable safety and tolerability profile over a 12-month treatment period.

Importantly, PTC518 also showed potential in slowing the progression of motor symptoms in HD patients. At the 5mg dosage, motor symptoms worsened by 2.0 points, while at the 10mg level, the worsening was limited to 1.3 points. For comparison, patients receiving a placebo experienced a more substantial worsening of 4.9 points.

Matthew Klein, CEO of PTC Therapeutics, emphasized the significance of these findings, stating, “The evidence of both CNS biomarker and early clinical effects at month 12 along with the continued favorable tolerability pro the promise of PTC518 to address the need for an effective and safe disease-modifying therapy for patients living with Huntington’s disease.”

The FDA's decision to lift the partial clinical hold came after a thorough review of the data. The hold was initially placed in October 2022 when the agency requested additional data to support the proposed dosing and duration for PTC518's 12-month study. Despite this, PTC continued patient enrollment in other global locations.

This development for PTC comes at a time when other companies working on Huntington’s disease treatments face challenges. For instance, earlier this month, Sage Therapeutics reported only slight numerical improvement in a Phase II trial of its oral NMDA receptor dalzanemdor. The lack of substantial data prompted cautious reactions from analysts, who described the results as “underwhelming” and expressed skepticism about the potential of Sage’s candidate.

The positive interim results for PTC518 mark a significant step forward for PTC Therapeutics and their efforts to develop a disease-modifying therapy for Huntington’s disease. The reduction in mHTT levels and the slowing of motor symptom progression, coupled with the drug's safety and tolerability, suggest that PTC518 could fill the critical need for an effective treatment for HD.