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 12-week and 12-month endpoints focused on safety, biomarker changes, and clinical outcomes.

• Two dose levels (5 mg and 10 mg) were tested in Stage 2 and early Stage 3 Huntington's disease patients.

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

• All subjects could enter a long-term open-label extension after study completion.

Efficacy and biomarker results

• Durable, dose-dependent lowering of mutant huntingtin (mHTT) protein in blood and CSF at 12 months: 22% at 5 mg and 43% at 10 mg in blood, with over 40% lowering in CSF at 10 mg.

• Early, dose-dependent clinical benefit observed on Total Motor Score (TMS), with 70% slowing of progression at 10 mg and TMS worsening of 2.0 (5mg) and 1.3 (10mg) vs. 4.9 for placebo.

• Favorable effects and trends seen on composite UHDRS, Total Functional Capacity, and other clinical assessments.

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

Safety and tolerability

• No dose-limiting toxicities, treatment-related serious adverse events, or NfL spikes at 12 months.

• Most common adverse events were mild and similar across all groups, including placebo, with nasopharyngitis, influenza, headache, and falls being most common.

• No grade 4 or 5 adverse events or peripheral neuropathy reported.