EMA’s CHMP upholds its negative opinion on masitinib for ALS
AB Science sought conditional marketing authorization as add-on treatment
An advisory committee from the European Medicines Agency (EMA) has upheld its opinion against granting conditional marketing authorization to AB Science’s masitinib as an oral add-on treatment for amyotrophic lateral sclerosis (ALS) in the European Union.
The decision was taken in a meeting by the Committee for Medicinal Products for Human Use (CHMP) this month after the company asked that the first negative opinion on masitinib be reexamined.
“We are thankful to the patients and physicians that supported the reexamination process as part of the EMA review. We did all these efforts for the patients,” Alain Moussy, AB Science’s co-founder and CEO, said in a company press release.
AB Science had also filed for reconsideration in Canada, where its regulatory agency decided against conditionally approving masitinib in February. The company has decided against continuing the reconsideration, however, after Health Canada considered the newly submitted analyses as new data, not new analyses of existing data, which is not permitted during the reconsideration process per the agency’s guidelines. Health Canada has offered the option of submitting a new application to address the unresolved issues, indicating a possible path forward for the therapy.
Masitinib is an inhibitor of a type of enzyme called tyrosine kinase, which activates molecular cues for immune cells to mount an inflammatory response. Inhibiting these enzymes should reduce inflammation and protect nerve cells from damage in ALS, slowing disease progression.
Masitinib and ALS disease progression
Applications submitted to EMA and Health Canada were supported by data from the AB10015 Phase 2/3 clinical study (NCT02588677), which tested two doses of masitinib (3 or 4.5 mg/kg) against a placebo in 394 adults with ALS. All received their assigned treatment twice daily for 48 weeks, or nearly a year, as an add-on to Rilutek (riluzole), an approved ALS treatment.
The trial’s main goal was to determine whether masitinib could slow disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R). But researchers focused mainly on a group of patients with normal-progressing disease, defined as a monthly decline in the ALSFRS-R score of less than 1.1 points. In this group, patients who received the 4.5 mg/kg dose had a 27% slower disease progression than those on a placebo, meeting the main goal.
Masitinib also led to significantly slower declines in quality of life and lung function in patients progressing normally, but no changes were observed in fast-progressing patients.
However, when all the patients were examined together regardless of their rate of disease progression, there was a group with mild or moderate ALS who showed the greatest benefit, living more than two years longer and progressing 42% slower with masitinib than with a placebo.
CHMP also expressed concerns with the analysis of normal progressors and of mild and moderate ALS patients.
As part of the reexamination in Europe, a Scientific Advisory Group for Neurology reviewed the data and agreed that the cutoff ALSFRS-R score of 1.1 points would be acceptable for distinguishing patients with normal or fast progression if properly pre-specified before the trial had started. This supports the design of the ongoing AB19001 Phase 3 clinical trial (NCT03127267), which is using the same cutoff to classify normal and fast progressors.
“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 in our compassionate use program,” Moussy said. “Now AB Science objective is to focus on the confirmatory phase 3 program of masitinib in ALS to reach full approval.”
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