Note: This story was updated Jan. 14, 2021, to note that pridopidine is no longer called Huntexil.
The findings were published in the Journal of Huntington’s Disease, in two studies: “Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study” and “Additional Safety and Exploratory Efficacy Data at 48 and 60 Months from Open-HART, an Open-Label Extension Study of Pridopidine in Huntington Disease.”
Pridopidine is a small molecule that activates the sigma-1 receptor, which is thought to have biological effects that protect nerve cells from damage. The medication was developed originally as a potential treatment to improve motor functions; however, emerging biological data has indicated it could have other effects. The therapy is currently being developed by Prilenia Therapeutics, which acquired it from Teva Pharmaceuticals in 2018.
The Phase 2 PRIDE-HD clinical trial (NCT02006472) tested various doses of pridopidine against placebo in people with Huntington’s. Originally designed as a 26-week trial to evaluate the medication’s effect on motor function, the trial was amended to a 52-week study after new data on pridopidine’s possible biological effects became available.
Now, researchers conducted a post hoc analysis (an analysis done after the trial is over) of data from PRIDE-HD to evaluate the effect of the medication on total functional capacity. This measurement, abbreviated TFC, assesses a person’s ability to function independently across five domains (work, finances, chores, daily living, and home and caregiver status). TFC is scored from zero to 13; higher scores indicate better function.
The analysis compared trial participants who were given placebo to those who received 45 mg pridopidine twice per day, which is expected to be the most effective dose based on biological data. In total, 55 participants given placebo and 48 given pridopidine completed the first 26 weeks of the trial; 41 on placebo and 37 on pridopidine completed the full 52 weeks.
Over the course of the trial, TFC in the placebo group gradually declined, which is typical of Huntington’s disease progression. At 52 weeks, average TFC scores in the placebo group decreased by 0.83 points, whereas in the pridopidine group, TFC scores were virtually unchanged (average 0.04 point increase). The difference between the groups was statistically significant. A similar trend was seen after 26 weeks of treatment; however, the difference between groups was not statistically significant at the earlier timepoint.
In people with early Huntington’s — defined as a starting TFC score of seven or higher — the effect of pridopidine was more pronounced: at 26 weeks, the average TFC score in the pridopidine group was 0.56 points higher than in the placebo group. At 52 weeks, the difference between the groups was 1.16 points. For this subset of participants, the difference was significant at both timepoints.
Further analyses showed that, among participants with early disease, pridopidine had a significant effect on every component of TFC score except work after 52 weeks.
“Participants receiving pridopidine 45 mg bid [twice daily] displayed virtually no decline in mean TFC over the course of 1 year, an effect particularly visible for patients with milder disease,” the researchers wrote.
Among all the participants, 47.3% on placebo had a worsening of TFC score after 52 weeks, significantly less than those on pridopidine (23.4%). Again, the difference was more pronounced among those with early disease (51.2% vs. 18.9%).
In the other study, researchers reported data from Open-HART (NCT01306929), an open-label extension study (in which all participants get the active medication) that evaluated long-term use of pridopidine. Among the initial group of 118 patients, 40 remained in the study after four years and 33 after five years.
Among Open-HART participants with early disease, the average TFC decline over five years was 1.8 points. Historical data suggest that untreated Huntington’s patients would experience a decline of five points over the same time frame — that difference is statistically significant.
The long-term data from Open-HART also indicate that the medication was safe and well-tolerated over five years of treatment. Most reported adverse side effects were mild or moderate; the most common were typical of Huntington’s (e.g., falls and anxiety).
“Pridopidine has demonstrated an excellent long-term safety profile and suggestion of improvement in clinical trials, as well as in exploratory analyses, where early HD populations appear to particularly benefit,” Andrew McGarry, MD, director of clinical development at Clintrex and co-author of both studies, said in a press release.
“In view of these promising data, the newly initiated Phase 3 study in HD will be of great interest to the entire HD community,” McGarry said.
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