Date: 2016-09-19
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of results at the 9th European Huntington Disease Network Plenary Meeting in The Hague
Company: Teva Pharmaceuticals (Israel)
Product: pridopidine
Action
mechanism: Pridopidine is an investigational, oral, small molecule being developed for the symptomatic treatment of Huntington's disease (HD). Teva intends to design and complete new clinical studies of pridopidine to assess its potential for symptomatic relief of HD. Earlier clinical studies of pridopidine conducted in the U.S., EU and Canada in patients with HD indicate a significant treatment effect on an important secondary endpoint, Total Motor Score (TMS). The drug has been discovered by the danish company Neurosearch. In October 2012, NeuroSearch and Teva have closed an asset transfer agreement concerning the sale of the Huntexil® project to Teva. NeuroSearch has received DKK 120.8 million in cash, and in addition Teva has placed DKK 28.7 million in escrow which will be released upon satisfactory transfer of the Huntexil® project.
In previous studies, where doses up to 45 mg bid were tested, pridopidine was well tolerated with an adverse event profile similar to placebo, and treatment with pridopidine was not associated with worsening of disease signs and symptoms.
Disease: motor impairment in patients with Huntington's disease
Therapeutic area: Neurodegenerative diseases - Rare diseases - Genetic diseases
Country: USA, Australia, Austria, Canada, Denmark,France, Germany, Italy, The Netherlands, Poland, Russian Federation, UK
Trial
details: The Pride-HD Study, a phase II, dose-finding, randomized, parallel-group, double-blind, placebo-controlled study, that aims to enroll approximately 400 patients at 30 sites across the globe and evaluate the safety and efficacy of pridopidine 45 mg, 67.5 mg, 90 mg, and 112.5 mg twice daily (bid) versus placebo for symptomatic treatment in patients with Huntington's disease. The primary objective will be to assess the efficacy of pridopidine on motor impairment after 26 weeks of treatment using the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score (TMS). The study will also examine the effect of treatment with pridopidine on the Physical Performance Test (PPT), as well as the safety and tolerability across the range of pridopidine doses in patients with HD during the 26 weeks of treatment.
Qualifying patients for The Pride-HD study must be 21 years of age or older, with an onset of HD after age 18 and must have a diagnosis of HD based on clinical features and the presence of =36 cytosine-adenosine-guanine (CAG) repeats in the HTT gene. (NCT02006472)
Latest
news: * On September 19, 2016, Teva Pharmaceutical Industries announced top-line results from the exploratory Phase 2 PRIDE-HD study. This 52-week, dose-ranging trial of pridopidine twice daily versus placebo study was directed at measuring improvement in motor function and the effect on Huntington's disease progression.
An unusually high placebo effect, extending beyond that expected from previous studies, limited the ability to determine treatment effects on assessments of Huntington's disease motor scores. Evidence of symptomatic impact, however, was seen in the early stage Huntington's disease patient sub-population, with improvement in Total Motor Score (TMS) and dystonia observed at 26 and 52 weeks in this patient sub-set (stage 1 HD) at specific doses.
The discovery of pridopidine's previously unknown mode of action as a potent agonist of the Sigma 1 Receptor (S1R) resulted in a change in PRIDE-HD study design, from a 26-week study focused on symptoms, to a 52-week study focused on exploring pridopidine's potential impact on disease progression, as measured by Total Functional Capacity (TFC). TFC is the most widely accepted and validated tool for assessing disease stage in Huntington's disease. It has been used as the endpoint in more than 10 previous clinical trials of drugs seeking to demonstrate an impact on Huntington's disease progression, none of which were successful.
This study showed a statistically significant impact on the endpoint of disease progression at 52 weeks following treatment with pridopidine at certain doses versus placebo, as measured by TFC. The effect of pridopidine was further evident in a sub-population of patients with early stage Huntington's disease, an effect first observed at 26 weeks.
Improvements were seen for early stage Huntington's disease patients in elements that make up TFC, such as ability to undertake domestic chores, activities of daily living and impact on ability to manage finances. Patients' mobility and ability to move around (ambulation) may have contributed to improved TFC scores, with multiple ambulation-related endpoints (such as gait, walking, ability to get up from sitting and walk, and stair climbing) demonstrating trends favoring pridopidine. Safety and tolerability were consistent with the safety profile seen in previous studies and compatible with continued development. No new safety findings were reported.
These results were presented at the 9th European Huntington Disease Network Plenary Meeting in The Hague on September 18, 2016 . 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 , M.D., M.P.H., Director of the Clinical & Translational Science Institute at the University of Rochester Medical Center .
The results seen in this exploratory study will need to be confirmed in a Phase 3 program that will be developed in collaboration with relevant regulatory agencies.
* On April 24, 2014, Teva Pharmaceutical Industries has announced the enrollment of the first patient in The Pride-HD study, a phase II, randomized, double-blind, placebo-controlled global study designed to evaluate the impact of pridopidine, an investigational medication, on motor impairment in patients with Huntington's disease (HD).
