PTC Therapeutics (PTCT) Study Result summary

Study design and objectives

• Phase 2 PIVOT-HD is a randomized, placebo-controlled study evaluating PTC518 in Huntington's disease, with two dose levels (5 mg and 10 mg), two patient cohorts (Stage 2 and early Stage 3), and endpoints at 12 weeks and 12 months focused on safety, biomarker changes, and clinical outcomes.

• The main objectives were to demonstrate durable, dose-dependent lowering of HTT protein, favorable CNS biomarker and clinical effects, and continued safety and tolerability at 12 months.

• Patient cohorts were balanced in age, gender, CAG repeat length, and functional capacity across treatment arms.

• All subjects completing PIVOT-HD are eligible for a long-term open-label extension.

Efficacy and biomarker results

• Durable, dose-dependent lowering of HTT/mutant HTT protein in blood and CSF was observed, with reductions reaching 22% at 5 mg and 43% at 10 mg in blood, and over 40% in CSF at 10 mg at 12 months.

• No treatment-related spikes in neurofilament light chain (NfL) were observed, and NfL levels remained consistent across groups.

• Striatal brain volume changes were similar across all groups, indicating no adverse impact on brain structure.

• Additional week 12 data confirmed dose-dependent mHTT lowering and consistent safety profile in expanded cohorts.

Clinical outcomes

• Early clinical benefit was observed, including a >70% reduction in TMS progression at 10 mg, with TMS worsening of 2.0 (5 mg) and 1.3 (10 mg) vs. 4.9 for placebo at 12 months.

• Favorable trends were seen in composite UHDRS (cUHDRS) and Total Functional Capacity (TFC) scores, with less worsening and smaller declines in treated groups compared to placebo.