Prilenia searches for positive signs as oral ALS drug fails to improve disease severity in phase 2

Prilenia Therapeutics’ amyotrophic lateral sclerosis (ALS) therapy did not improve disease severity, but the biotech is pointing to “positive trends” from an exploratory analysis, suggesting that some patients' experienced a slower decline.

Pridopidine was being tested in the phase 2 HEALEY ALS Platform Trial, according to the company’s Thursday press release. ALS causes the loss of motor neurons, leading to muscle weakness, twitching, slurring of speech and other symptoms. The drug failed to improve functioning on a scale that measured ALS severity including speech disruptions, handwriting, swallowing, walking and other daily tasks. 

The biotech, however, conducted a posthoc analysis and found that some patients who were rapidly declining had “substantially less decline” with pridopidine when compared to those who received placebo. There were also “trends” in a prespecified analysis suggesting that patients had less decline on respiratory function, speech and speaking rate.

Prilenia also pointed to a known biomarker in neurodegenerative diseases, neurofilament light, which was reduced in the rapidly declining patients taking pridopidine.

As for safety, results for the oral medication were similar to previous studies showing pridopidine was well tolerated with no new safety signals observed.

The principal investigator and sponsor of the study, Merit Cudkowicz, M.D., noted in the press release that these results “deserve further exploration,” and the impact on speech is particularly relevant to ALS patients. Cudkowicz serves as director of the Sean M. Healey & AMG Center for ALS, chief of the Department of Neurology at Massachusetts General Hospital, and is the Julieanne Dorn Professor of Neurology at Harvard Medical School.

“In particular, the impact of pridopidine on speech measures was notable, likely due to its S1R mechanism of action,” Cudkowicz said. “Speech is a highly clinically relevant endpoint in ALS studies, and more than 80% of ALS patients become speech impaired, which significantly impacts their quality of life.”

CEO Michael Hayden said in the release that the results corroborate testing in mice that suggested pridopidine can impact ALS.

“This study adds to the growing body of evidence that S1R activation has beneficial neuroprotective effects, and this gives us a compelling rationale for further development of pridopidine in ALS,” Hayden said. “Prilenia intends to continue its evaluation of pridopidine in ALS, and our future clinical program will build on the important learnings from the HEALEY ALS Platform Trial.”

Prilenia is conducting additional analyses of the data and considering next steps, according to the release. The company is also testing pridopidine in a phase 3 trial for Huntington's disease and in early and preclinical research for other neurodegenerative disorders.