Prilenia Therapeutics, Waltham, Massachusetts and Naarden, Netherlands is a biotechnology company with a focus on developing therapeutics to treat neurodevelopmental disorders and neurodegenerative diseases.

Prilenia presented data this month at the Annual ALS Research Summit in California that supports a planned Phase 3 study of pridopidine, a potential treatment for amyotrophic lateral sclerosis (ALS). Biospace reports that the company has been in discussions with various regulatory agencies with respect to the next stage in the developing pridopidine. Its planned Phase 3 trial should begin in 2024.

About Pridopidine

Pridopidine is a small molecule and a discriminating sigma-1 receptor (S1R) being developed as a treatment for Huntington’s disease and ALS. Several recessive, loss-of-function mutations in S1R have been associated with ALS/frontotemporal dementia (ALS/FTD). The mutation, which is a genetic lesion, causes a reduction in the activity of a gene. It either prevents its production or decreases its activity.

S1R expresses strongly in the spinal cord and brain, regions that are important for speech and bulbar function, and are implicated in the disease. When symptoms begin to appear in facial and neck muscles it is known as the “bulbar” onset from ALS. Prilenia founder and CEO Michael Hayden M.D. noted that the clinical data which has been generated thus far indicates that pridopidine gives every indication of slowing disease progression.

However, pridopidine was not able to meet the primary endpoint. Secondary endpoints involved respiration, speech, and quality of life measurements. Yet data from the HEALEY ALS Trial evaluating efficacy and safety of pridopidine within 18 months from the onset of symptoms, found that pridopidine was credited with slowing progression of disease in relation to placebo. Other benefits for a specific subgroup were improvement in speech which is considered a clinically relevant ALS endpoint.

Overall disease severity in ALS and bulbar are directly related to speech measurement. Also, at week number 24 in the Phase 2 study of patients whose disease had been progressing rapidly, the researchers found that disease progression slowed 41% compared to placebo. A Cox Hazard Ratio analysis indicated a 57% improved survival benefit. Previously, reduced disease progression had been observed at eight weeks and sixteen weeks.

The NIH Grant

Two hundred ALS patients in the United States who are ineligible for participation in clinical trials will receive expanded access to pridopidine via an NIH grant.

Topline Results

Preliminary results of the Phase II study had been announced previously. There were no severe adverse events associated with pridopidine.

About S1R and Pridopidine

Pridopidine is a highly selective, oral, and investigational S1R agonist that is expressed in the spinal cord and brain. S1R regulates various processes that are impacted in ALS and several neurodegenerative diseases. As a result of S1R activation by pridopidine, multiple cellular pathways are stimulated. These pathways are essential to survival and protect nerve cells from impairment of function.

The Orphan Drug Act

Prilenia has received the FDA’s Orphan Drug designation for pridopidine to treat Huntington’s disease and ALS in the EU and U.S. The Orphan Drug Act incentivizes the development of new drugs for rare diseases. The FDA’s fast track designation was also awarded to Prilenia to treat Huntington’s disease. Pridopidine has not yet been approved in the United States or the European Union.

The most commonly used criteria for ALS diagnosis are the revised El Escorial criteria. Its four anatomical regions are bulbar, cervical, thoracic and lumbar. In order to be eligible for the trial, participants must have El Escorial probable, possible, or ALS definite symptom onset.

The revised El Escorial criteria lists ALS Inclusion criteria as:

• Diagnostic Category Inclusion Criteria
• Definite ALS Upper motor neuron and lower motor neuron signs in three anatomical regions
• Probable ALS Upper motor neuron and lower motor neuron signs in a minimum of two anatomical regions