European Agency Issues Negative Opinion on Marketing Authorization for Masitinib in ALS

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) issued a negative opinion on the conditional marketing authorization of masitinib for the treatment of amyotrophic lateral sclerosis (ALS), the therapy’s maker, AB Science, recently announced in a press release.

Masitinib is a tyrosine kinase inhibitor (TKI) being developed by AB Science to treat symptoms of ALS. The oral therapy targets cells of the immune system (the mast cells and macrophages). It works by blocking the activation of proteins (tyrosine kinases) that are thought to play a role in inflammation and chronic inflammatory states.

Grounds for CHMP’s negative opinion were based on three factors:

  • the reliability of the data was not robust enough to support a registration (based on an inspection carried out on two of the main clinical investigation centers of the study).
  • the clinical relevance of the distinction made between patients with “normal” progression (85 percent of patients in the study) and those with “rapid” progression (15 percent of the patients) was not demonstrated.
  • there was a suspicion of bias regarding the primary analysis of the ALS Functional Rating Scale (ALSFRS) score for patients who stopped the study prematurely. ALSFRS-R measures abilities such as walking, speech, hand control, and respiration.

AB Science’s next step will be to provide additional data through a re-examination procedure to address these issues, after which CHMP will deliver a second opinion in July 2018.

EMA accepted the conditional marketing authorization application for masitinib to treat ALS in October 2016. If approved, the authorization allows early access to a therapy for which immediate need outweighs the risk of less comprehensive data than normally required.

Acceptance of the application was based on results from a Phase 2/3 clinical trial (NCT02588677), in which masitinib met its primary goal of improving the functioning of ALS patients, and on data from additional preclinical studies.

The study included 394 ALS patients who were randomized to treatment with either 4.5 mg/kg/day of masitinib and Rilutek (riluzole), 3 mg/kg/day of masitinib and Rilutek, or placebo and Rilutek, for up to 48 weeks.

Results showed that a daily dose of 4.5 mg/kg in combination with Rilutek significantly improved patients’ quality of life and survival. The study was published in the Journal of Neuroinflammation.

The U.S. Food and Drug Administration granted masitinib orphan drug status in 2015, and the EMA followed with its own orphan drug designation in 2016.