Phase 2 Study Finds Evidence of Slowed Disease Progression in Huntington’s Patients
Teva Pharmaceutical presented encouraging top-line data from PRIDE-HD, a Phase 2 clinical trial evaluating the impact of pridopidine, an oral medication, on motor impairment in patients with Huntington’s disease (HD). Teva is now preparing for a larger clinical study in Huntington’s.
The presentation took place at the 9th European Huntington Disease Network Plenary Meeting in The Hague, Netherlands on Sept. 18.
PRIDE-HD (NCT0200647) was initially designed as a 26-week, dose-escalating, double-blind, and placebo-controlled study evaluating the safety and efficacy of pridopidine at 45 mg, 67.5 mg, 90 mg, and 112.5 mg twice-daily, versus placebo, for symptomatic treatment in 408 Huntington’s patients.
Its primary endpoint was the change from baseline in Unified Huntington’s Disease Rating Scale-Total Motor Score (UHDRS-TMS) at week 26. Secondary endpoints consisted of the change from baseline in modified Physical Performance Test (mPPT) at week 26 and the summary of participants with adverse events.
But in contrast to what researchers’ expected, based on previous studies, placebo treatment in PRIDE-HD exerted an unusually high effect, limiting their ability to determine the effects of the treatment on motor scores. Further results revealed that in the early stage patient sub-population (stage 1 HD), at 26 and 52 weeks, treatment with pridopidine at specific doses improved the Total Motor Score (TMS) and dystonia (movement disorder).
The finding that pridopidine is an agonist of the Sigma 1 Receptor (S1R) altered the trial design, from a 26-week symptom-focused study to a 52-week study focused on exploring the impact of the drug on HD progression, as measured by Total Functional Capacity (TFC). TFC is a standardized scale, ranging from 13 (normal) to 0 (severe disability), used to assess capacity to work, handle finances, perform domestic chores and self-care tasks, and live independently.
Results showed that pridopidine treatment, compared to placebo, resulted in a statistically significant impact on disease progression as assessed by TFC, the company reported in its press release. This effect was again most marked in the early stage sub-group of patients, who showed an improved ability to undertake domestic chores, daily living activities, and manage finances at 52 weeks.
These observed improvements may have resulted from patients’ mobility and ability to move around, the company reported, with multiple ambulation-related endpoints (such as gait, walking, ability to get up from sitting and walk, and stair climbing) demonstrating trends favoring pridopidine.
“I am encouraged by these results, which provide us with clear insights into the approach to be taken in Phase 3 development,” Michael Hayden, president and chief scientific officer of Teva Global R&D, said in the release. “My obvious hope is that this will provide the HD community with a medicine capable of slowing down the progression of this devastating disease.”
Consistent with the findings from previous studies, pridopidine was well-tolerated by study participants and had an adverse event profile similar to placebo.
Full results from PRIDE-HD will be submitted for publication in a scientific journal.
“These study results are very important for the HD community and for the continued development of pridopidine. Firstly, pridopidine’s safety profile has been confirmed and extended. Secondly, we now have a clearer idea of the dosages to study in Phase 3. Lastly, we have some of the most encouraging evidence to date about an intervention which may slow the inexorable functional decline of HD,” said Karl Kieburtz, MD, MPH, director of the Clinical & Translational Science Institute at the University of Rochester Medical Center.
Pridopidine is a drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. These compounds may counteract the effects of excessive or insufficient dopaminergic transmission, and are being investigated to treat neurological and psychiatric disorders characterized by altered dopaminergic transmission, such as Huntington’s disease.