Pridopidine for ALS

What is pridopidine for ALS?

Pridopidine is an experimental oral therapy that is being tested as a potential treatment for amyotrophic lateral sclerosis (ALS).

In ALS, the specialized nerve cells that control movement, called motor neurons, become damaged and die off. Progressively worsening muscle weakness leads to movement problems and other symptoms, including issues with swallowing, speaking, and breathing.

Pridopidine is designed to bind to and activate the sigma-1 receptor (S1R), a protein found throughout the brain and spinal cord that regulates processes crucial for the survival and function of nerve cells, including motor neurons. This is expected to help promote motor neuron survival in ALS by reducing inflammation and cellular stress while also enhancing cellular energy production, toxic protein clearance, and other protective factors.

Prilenia Therapeutics is codeveloping pridopidine with Ferrer in certain international markets. The therapy is in Phase 3 testing for ALS, and is also in development for Huntington’s disease and potentially other neurodegenerative conditions.

The medication holds orphan drug status for ALS in both the U.S. and Europe, and fast track designation in the U.S., which are statuses intended to expedite its clinical development.

Therapy snapshot

How will pridopidine be administered in ALS?

In clinical trials for ALS, pridopidine has been administered as oral capsules. The starting dose is one capsule (45 mg) per day for the first two weeks, after which participants receive two capsules (90 mg total) per day during maintenance dosing.

Pridopidine in ALS clinical trials

Pridopidine is being evaluated in a Phase 3 clinical trial called PREVAiLS (NCT07322003), involving around 500 adults with definite or probable ALS whose symptoms started within the last 1.5 years and whose disease is quickly progressing.

Participants will receive pridopidine or a placebo for nearly a year (48 weeks), with the main goal of evaluating whether the treatment can slow disease progression, as assessed by score changes on the ALS Functional Rating Scale-Revised (ALSFRS-R) adjusted for mortality. After the main treatment period, all participants will be eligible to receive pridopidine for another 48 weeks.

The study population for PREVAiLS was supported by data from the pridopidine arm (NCT04615923) of the Phase 2/3 HEALEY ALS Platform Trial (NCT04297683), in which adults with ALS received pridopidine or a placebo for about six months. Those who completed the trial were given the option to enter an open-label extension, in which all received pridopidine.

Results included the following:

• Pridopidine did not ease disease severity compared with the placebo, as assessed with ALSFRS-R score changes and survival, failing to meet the study’s main goal. It also did not significantly slow declines in muscle strength or lung function, but did lead to significant improvements in certain aspects of speech.
• The therapy was associated with significantly slower ALSFRS-R declines than the placebo among the subgroup of participants with probable or definite ALS who had symptom onset in the past 1.5 years and rapidly progressing symptoms.
• Among participants with probable or definite ALS who were early in the disease course, those who received pridopidine throughout the main trial and open-label period tended to survive longer than those who began taking the medication during the open-label portion. The median survival time increased from approximately 300 days to 600 days, although this difference didn’t achieve statistical significance.

Pridopidine side effects

In the HEALEY trial, the most common safety events included:

• falls
• muscle weakness
• neuromuscular problems
• constipation
• diarrhea
• nausea
• difficulty swallowing
• fatigue

Most of these side effects occurred at similar rates in the pridopidine and placebo groups.