AB Science Announces Significant Survival Data for Masitinib in ALS

ALS

This afternoon – this evening Paris-time – AB Science announced the publication of long-term follow-up data showing that lead compound, masitinib, extended survival in Amyotrophic Lateral Sclerosis (ALS) patients by 25 months compared to placebo when treatment was started early. 

The data, published in the peer-reviewed journal, Therapeutic Advances in Neurological Disorders  is the latest to be reported from AB Science’s multicenter phase II/III study, AB10015. The trial, assessing masitinib as an add-on therapy to riluzole, commenced in 2013 and wrapped in 2016.

Riluzole, approved in 1995, is one of only two drugs authorized by the U.S. Food and Drug Administration (FDA) to treat ALS. The other is Mitsubishi Tanabe’s Radicava (edaravone), which the agency authorized in 2017. 

The survival analysis, which followed all patients originally randomized in the study for an average of 75 months from the date of diagnosis, demonstrated that those treated with a regimen of riluzole plus 4.5 mg/kg/day of masitinib (n=50), survived 25 months longer than those treated with riluzole alone. 

In 2020, AB Science published results demonstrating that the addition of masitinib correlated in a -27% decrease in disease progression among normal progressors, meaning patients with a baseline progression of <1.1 point/month on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).  

With these latest results, AB Science has further established the sweet spot for masitinib in ALS. This patient population closely corresponds to that of its confirmatory phase 3 study, AB19001, which also consists of patients with mild or moderate ALS. No longer-term survival was observed when the population was expanded to disregard disease severity. 

“These long-term survival data, with an average follow-up of 75 months since diagnosis, suggest that masitinib can offer a substantial survival benefit when treatment is initiated before severe loss of functionality,” stated Professor Albert Ludolph, chairman of the department of neurology at the University Hospital and Medical Faculty of Ulm and principal investigator of the confirmatory study.

Masitinib, a tyrosine kinase inhibitor, is the only drug of its kind in late-stage development or ALS. It provides neuroprotection in both the central and peripheral nervous systems, via the inhibition of mast cell and microglia/macrophage activity. The pharmacological action of masitinib has been shown to slow microglial-mediated disease progression, which again supports its value at an early juncture.

“The goal is to prevent the deterioration and the loss of the connection between the muscles and the nerve. If you stop the process, the patient may improve, but if it’s too late, the patient won’t improve because if the nerve is gone, it’s gone,” said Dr. Olivier Hermine, MD, PhD., president of AB Science’s scientific committee and Professor of Hematology at the University Paris V-René Descartes.

Combination approaches such as this one echo the calls of ALS experts like Dr. Melanie Leitner, chief scientific officer at the ALS Investment Fund, who believe that this is the key to effectively treating the disease.

“Unfortunately, there are many pathways, many processes going wrong in the cell, and we probably are going to need to have a way to remedy across these,” Leitner told BioSpace in a previous interview. “I think the vision is that, as we have therapies that have a benefit and can slow progression, that will give us the option and the opportunity to test combinations.”  

That being said, Hermine is confident that masitinib can stand on its own and also noted the ethical implications of the use of a placebo protocol in a rapidly terminal disease such as ALS.

Hermine is hopeful of completing enrolment for the confirmatory trial, AB19001, in the near future and ultimately reaching its conclusion sometime in the 2023 time frame. 

Masitinib is a drug with potential in a wide range of diseases. AB Science recently presented results from a Phase III study of masitinib in pancreatic cancer with pain, where meaningful overall survival was increased by 1.8 months in combination with gemcitabine. The compound is also in late-stage development for Multiple Sclerosis (MS) and Alzheimer’s disease.  

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