Treatment for Huntington’s Disease achieves primary end point in clinical trial
Results from the Phase 2 PIVOT-HD study of PTC518 (votoplam) in Stage 2 and Stage 3 Huntington’s disease (HD) patients demonstrated that the treatment met its primary endpoint of reduction in blood Huntingtin (HTT) protein levels.
The treatment showed a reduction in HTT protein levels at Week 12 and favourable safety and tolerability.
The 12-month data from the Stage 2 patients were also consistent with the previously reported dose-dependent lowering of HTT protein and dose-dependent trends across clinical scales, according to PTC Therapeutics which carried out the trial.
“These PIVOT-HD results confirm that PTC518 lowers Huntingtin protein and shows early signals of clinical benefit with a favourable safety profile,” said Matthew Klein, CEO at PTC Therapeutics.
“In addition, at 24 months, we observed favourable dose-dependent trends on the cUHDRS and the TFC and SDMT subscales relative to natural history as well as dose-dependent lowering of neurofilament light chain protein.
“We look forward to discussions on the next development and regulatory steps including the potential for accelerated approval as we work to potentially bring the first disease-modifying therapy to those affected by Huntington’s disease.”
Results from the full 12-month cohort demonstrate dose-dependent lowering in blood HTT levels, with 23 per cent at the 5mg dose level for both Stage 2 and 3 patients and 39 per cent and 36 per cent at the 10mg dose level for Stage 2 and 3 patients.
For Stage 2 patients, there were dose-dependent trends of benefit on clinical scales including the Composite Unified Huntington’s Disease Rating Scale (cUHDRS) and Total Motor Score (TMS) subscale.
For Stage 3 patients, there were trends favouring the 5mg dose group relative to placebo, but not the 10mg dose group, suggesting that treatment effect may differ in Stage 3 patients relative to Stage 2 patients.
For all dose levels and disease stages, PTC518 showed a favourable safety and tolerability profile with no treatment-related serious adverse events or neurofilament light chain protein (NfL) spikes.
In addition, 24-month treatment data from the patients on whom data were shared last year (N=21) demonstrate signals of dose-dependent trends on the cUHDRS, Total Function Capacity (TFC) and Symbol Digit Modalities Test (SDMT) subscales when compared to a propensity matched natural history cohort from the ENROLL-HD Registry.
At Month 24, there was also dose-dependent lowering of plasma NfL from baseline of -8.9 per cent for the 5mg dose level and -14 per cent for 10mg dose level.
According to the company, following 12 months, patients were eligible to enroll in a long-term extension study in which all subjects would receive PTC518. Those originally randomised to 5mg and 10mg would continue at that dose level, and those initially randomised to placebo would be randomised 1:1 to 5mg or 10mg.
