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Front Aging Neurosci. 2017 Mar 22;9:68. doi: 10.3389/fnagi.2017.00068. eCollection 2017.

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment?

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AB Science Paris, France.
AB ScienceParis, France; Imagine Institute, Necker HospitalParis, France; INSERM, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, UMR 1163Paris, France; Imagine Institute, Paris Descartes-Sorbonne Paris Cité UniversityParis, France; CNRS, ERL 8254Paris, France; Laboratory of Excellence GR-ExParis, France; Equipe Labélisée par la Ligue Nationale Contre le CancerParis, France; Department of Hematology, Necker HospitalParis, France.


Amyotrophic lateral sclerosis (ALS) is a devastating condition with an estimated mortality of 30,000 patients a year worldwide. The median reported survival time since onset ranges from 24 to 48 months. Riluzole is the only currently approved mildly efficacious treatment. Riluzole received marketing authorization in 1995 in the USA and in 1996 in Europe. In the years that followed, over 60 molecules have been investigated as a possible treatment for ALS. Despite significant research efforts, the overwhelming majority of human clinical trials (CTs) have failed to demonstrate clinical efficacy. In the past year, oral masitinib and intravenous edaravone have emerged as promising new therapeutics with claimed efficacy in CTs in ALS patients. Given their advanced phase of clinical development one may consider these drugs as the most likely near-term additions to the therapeutic arsenal available for patients with ALS. In terms of patient inclusion, CT with masitinib recruited a wider, more representative, less restrictive patient population in comparison to the only successful edaravone CT (edaravone eligibility criteria represents only 18% of masitinib study patients). The present manuscript reviews >50 CTs conducted in the last 20 years since riluzole was first approved. A special emphasis is put on the analysis of existing evidence in support of the clinical efficacy of edaravone and masitinib and the possible implications of an eventual marketing authorisation in the treatment of ALS.


amyotrophic lateral sclerosis (ALS); clinical trial; edaravone; masitinib; motor neuron disease; riluzole

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