PTC Therapeutics Reports Mixed Results for Novartis-Partnered Huntington's Drug

PTC Therapeutics has announced phase 2 results for its Huntington's disease candidate PTC518, developed in partnership with Novartis. The data reveal a significant reduction in blood Huntingtin (HTT) protein levels, meeting the study's primary endpoint. However, the market response has been lukewarm, with investors expressing skepticism about the drug's path to accelerated approval.

Study Results and Market Reaction

The phase 2 trial compared two doses of PTC518, a small-molecule splicing modifier, to placebo in patients with stage 2 or stage 3 Huntington's disease. After 12 weeks, significant reductions in blood HTT protein levels were observed, with these reductions persisting through the 12-month analysis. Levels were down between 23% and 39% from baseline across the doses and patient populations.

Despite these promising biomarker results, PTC's stock fell almost 19% to $40.65 following the announcement. This decline reflects investor uncertainty about the correlation between HTT reductions and clinical outcomes, as well as doubts about PTC518's ability to significantly slow the rate of clinical decline.

Clinical Outcomes and Future Prospects

PTC reported "dose-dependent trends of benefit on clinical scales" for stage 2 patients, who account for approximately 85% of the total Huntington's disease population. The effect on stage 3 patients was less clear, with trends favoring the low dose but not the high dose.

PTC CEO Matthew Klein, M.D., emphasized the drug's mechanism of action, stating, "We know we're getting HTT lowering and the drug is working as it's supposed to work." However, questions remain about the potential for disease modification in late-stage patients and the time required to observe clear and consistent signals.

Regulatory Path and Partnership with Novartis

The company plans to discuss the data with Novartis, which paid $1 billion upfront for PTC518 last year, before outlining next steps. Novartis CEO Vas Narasimhan has previously indicated that improvements in clinical endpoints would be necessary to file for approval using the phase 2 data. Alternatively, a phase 3 trial may be required before seeking regulatory approval.

While William Blair analysts believe the biomarker and clinical outcomes data at 12 and 24 months in stage 2 patients may be sufficient for productive conversations with the FDA, the path forward for PTC518 remains uncertain. The pharmaceutical industry will be watching closely as PTC Therapeutics and Novartis navigate the complex landscape of Huntington's disease drug development.