EMA Confirms Rejection of Neurodegenerative Disease Drugs

The European Medicines Agency (EMA) has upheld an earlier recommendation to deny marketing authorization for Masitinib AB Science (masitinib), an oral treatment for amyotrophic lateral sclerosis (ALS). 

In a meeting on October 17, the EMA’s Committee for Medicinal Products for Human Use (CHMP) reaffirmed its concerns about the reliability of the data supporting the drug. The agency said these issues were first raised in June 2024 and persisted after the data was reassessed at the request of the drug’s manufacturer, AB Science.

ALS is a neurodegenerative, life-threatening disease characterized by progressive muscular paralysis caused by the degeneration of motor neurons. 

Masitinib is a tyrosine kinase inhibitor intended to reduce inflammation and protect nerve cells from damage, potentially slowing the progression of ALS symptoms.

To support its application, the manufacturer presented results from a study, published in 2021 in the journal Therapeutic Advances in Neurological Disorders.  The trial involved394 adults with ALS who were randomly assigned to receive either masitinib or placebo for 48 weeks. All participants also received riluzole. The main measure of effectiveness was the ALSFRS-R score, a measure of ALS symptoms that affect patients’ daily living, over 48 weeks.

EMA’s Concerns

During its initial evaluation, the EMA said the study failed to show a difference between the medicine and placebo in the main measure of effectiveness for the total study population. Also, methodological issues were identified during inspections, it said. These concerns remained after a re-evaluation of the data, leading the regulator to conclude that the drug’s benefits did not outweigh its risks.

Commenting on the decision in a press release, Alain Moussy, CEO and co-founder of AB Science said, “We are convinced that masitinib is a promising drug when we see patients from the study surviving with the drugs for more than 10 years.” AB Science’s objective would be to focus on a phase 3 trial, he added.

Non-renewal of Duchenne Muscular Dystrophy Medicine Authorization

At its same meeting, the CHMP also confirmed its previous recommendation to not renew the conditional marketing authorization for Translarna (ataluren), a treatment for patients with Duchenne muscular dystrophy (DMD).

DMD is a rare genetic disorder that causes a progressive loss of muscle function, eventually leading to death due to respiratory muscle weakness or cardiomyopathy. It is a disease for which very few treatment options are available.

Translarna was authorized in the European Union in 2014 for the treatment of patients with DMD whose disease is caused by a nonsense mutation in the dystrophin gene. The drug’s active substance, ataluren, helps cells bypass the mutation to produce functional dystrophin protein.

Following multiple reviews and new trial data, the EMA concluded that Translarna’s efficacy could not be confirmed. As a result, the drug’s conditional marketing authorization will not be renewed, and it will no longer be available in the European Union.

Confirmation of recommendations made by the CHMP are subject to ratification by the European Commission.

Peter Russell has been a journalist for 40 years covering international news, health, medicine, and national politics on radio, TV, and online.