Phase 3 trial of masitinib can now launch in US, some EU countries
AB Science's confirmatory trial seeks 408 people with normally progressing ALS
AB Science has been cleared to start its confirmatory Phase 3 trial of masitinib for people with amyotrophic lateral sclerosis (ALS) in the U.S. and certain European countries.
The company announced plans for the Phase 3 AB23005 trial earlier this year, noting then that the trial had already been authorized by the U.S. Food and Drug Administration and validated by the European Medicines Agency.
In Europe, individual countries then need to clear the trial’s launch. So far, Spain, Greece, and Slovenia have given that authorization, according to AB Science.
AB23005 will compare the safety and efficacy of masitinib against a placebo among more than 400 ALS patients with normally progressing disease who are also being treated with the ALS therapy riluzole (sold as Tiglutik and generics).
Study design ‘based on strong clinical and preclinical data’
“Masitinib ALS study AB23005 has great potential because [its] design is based on strong clinical and preclinical data,” Albert Ludolph, MD, PhD, of the University of Ulm in Germany and the trial’s principal investigator, said in a company press release.
Ludolph noted the trial’s launch is supported by promising survival data from a previous Phase 2/3 clinical trial, as well as preclinical studies that provide “compelling insight into masitinib’s mechanism of action in ALS.”
Masitinib is an oral therapy designed to slow ALS progression by inhibiting tyrosine kinases, a group of enzymes critical for the function of immune cells believed to drive inflammation and nerve cell damage in ALS.
A Phase 2/3 trial called AB10015 (NCT02588677) tested two doses of masitinib against a placebo — all given as an add-on to riluzole tablets — among adults with ALS. Disease progression was monitored with the ALS Functional Rating Scale-Revised (ALSFRS-R) scale.
The high dose of masitinib (4.5 mg/kg) significantly slowed disease progression compared with the placebo among participants with normally progressing disease, defined as ALSFRS-R scores that had declined by less than 1.1 points per month from the time of disease onset to the study’s start.
Masitinib was particularly beneficial in those who had lost fewer functional abilities. Among people with normally progressing disease who had not yet completely lost function on any individual ALSFRS-R component, the high dose of masitinib led to more than a year’s survival benefit relative to the placebo.
However, applications for masitinib’s regulatory approval in the European Union and in Canada based on these findings received negative opinions, which prompted AB Science to consider a confirmatory Phase 3 trial to further demonstrate the therapy’s benefits in its target population.
A Phase 3 trial called AB19001 clinical trial (NCT03127267) was planned, but had trouble getting off the ground due to slow recruitment. U.S. and European regulators recommended the launch of an entirely new study to overcome certain enrollment barriers.
Enrolling participants with normally progressing ALS, some physical function
Thus, the company started planning for AB23005, which will enroll about 408 people with ALS.
In line with the group that benefited most from masitinib in the earlier trial, participants eligible for AB23005 must have normally progressing disease and not have completely lost physical function, meaning they’ll have a score of at least 1 on all 12 items of the ALSFRS-R.
This subgroup of patients represents around 75% of all people with ALS, and the inclusion criteria were agreed upon in consultation with European health authorities, according to AB Science.
Enrolled participants will be randomly assigned to receive oral masitinib (4.5 mg/kg) or a placebo once daily for 48 weeks (nearly a year), on top of standard riluzole treatment.
Participants in the U.S. who are already on Radicava or Radicava ORS (edaravone) may continue using it. The previously planned Phase 3 AB19001 trial didn’t allow that, which was considered one of the barriers to enrollment.
The study will mainly aim to evaluate disease progression, assessed with the ALSFRS-R and the Combined Assessment of Function and Survival. Quality of life, survival, and disease biomarkers will also be assessed.
Masitinib has received orphan drug designation for ALS in the U.S. and Europe, a status that offers financial and regulatory incentives to speed the development of therapies for rare diseases. Such a status may be sought in Japan, according to the company.
AB Science also holds patents covering the use of masitinib in all areas where the treatment could be marketed until at least 2037, including in the U.S., Europe, Japan, and several other regions globally.
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