The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital and the Northeast ALS (NEALS) Consortium announced topline results from Regimen D of the HEALEY ALS Platform Trial, which is evaluating pridopidine versus placebo in adults with ALS.

The phase 2 trial failed to meet its primary and key secondary endpoints. However, beneficial effects were observed across several secondary and exploratory endpoints, including improvements in speech and bulbar function, according to the researchers. In addition, no safety issues were found in terms of tolerability, serious and non-serious adverse events, laboratory tests or vital signs.

Pridopidine is an oral, small molecule developed by Prilenia Therapeutics that is taken twice a day. The drug selectively activates the sigma-1 receptor (S1R), which is found in abundance in the brainstem and spinal cord, areas important for bulbar, speech and limb function. This activation can positively influence key cellular pathways that are commonly impaired in people with ALS.

Preclinical research funded by The ALS Association’s Lawrence and Isabel Barnett Drug Development Program explored if pridopidine is neuroprotective and can strengthen connections between neurons. This is just one example of how the Association’s investment in early-stage research helps “de-risk” drug development and move new therapeutics toward clinical evaluation.

The initial results from the HEALEY trial showed no significant difference in overall function as measured by the revised ALS functional rating scale (ALSFRS-R) between pridopidine and placebo after 24 weeks of treatment. Changes in muscle strength, respiratory function and survival were also similar between the two groups.

In post-hoc analyses, the researchers did observe a trend toward greater benefit of pridopidine treatment among participants who were within 18 months of onset of symptomatic weakness and among those within 18 months of onset who also met El Escorial criteria for definite ALS. In addition, trends for slower decline in the ALSFRS-R respiratory sub-scale were seen in all participants. Benefits also were observed in quantitative speech measures with significant improvement in speaking rate and articulation rate.

“The positive results on speech and bulbar function, and on overall function and breathing in people earlier in disease course, are very encouraging and deserve further investigation in a phase III trial. Those are sensitive measures of disease progression and may indicate a general benefit of pridopidine that we were not able to detect in this study,” said Merit Cudkowicz, M.D., principal investigator and sponsor of the HEALEY ALS Platform Trial, in a press release.

Additional analyses are underway, including evaluation of data from the open-label extension study, which remains ongoing. Prilenia has indicated it is exploring potential next steps for pridopidine in ALS.