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The developer of the supplementary treatment masitinib for amyotrophic lateral sclerosis (ALS) has been given permission to request Health Canada to reconsider its previous decision against approving the oral therapy.
AB Science, the company behind masitinib, has been granted eligibility for reconsideration by the Canadian regulatory agency. This means that AB Science now has a 45-day window to submit a new request seeking approval for the drug.
The company has already engaged in discussions with Health Canada regarding the reconsideration process, as mentioned in a press release. As part of this reassessment, new evaluators will review the approval decision based on the existing data, which could take up to six months.
AB Science highlighted that the main focus of the reconsideration lies in addressing missing data concerns. They emphasized that analyses have demonstrated the therapy's success in earlier research.
This move by Health Canada comes after AB Science's initial request for masitinib's approval in 2022. However, the agency paused its review shortly afterward, citing the need for additional information. The review resumed in 2023 after a revised application was submitted but ended with a rejection in February.
Interestingly, regulatory authorities in the European Union also delayed their decision on masitinib, with a potential decision expected by June.
Masitinib is an oral medication designed to inhibit enzymes associated with inflammation and nerve cell degeneration in ALS. It is being explored as an additional treatment alongside riluzole, the only therapy currently proven to slow disease progression and extend survival in ALS patients.
Dr. Albert Ludolph, the principal investigator of the Phase 3 trial testing masitinib, expressed disappointment over recent failures in ALS treatment trials. He stressed the importance of learning from these setbacks to advance therapeutic approaches.
AB Science's applications were based on data from the AB10015 Phase 3 trial, involving 394 ALS patients. The study compared two doses of masitinib against a placebo, administered alongside standard ALS medication.
Results indicated that the higher dose of masitinib significantly outperformed the placebo in slowing physical decline, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R) scores after one year.
However, Health Canada raised concerns about the data from the AB10015 trial. Firstly, they noted a considerable amount of missing data in the year-long study, which raised questions about the validity of the results. AB Science countered by highlighting sensitivity analyses that supported masitinib's efficacy when considering the missing data conservatively.
Secondly, Health Canada questioned the reliability of findings from a subgroup of patients defined post hoc as "patients with ALS prior to any loss of function." While masitinib showed significant survival benefits in this subgroup, Health Canada considered the findings unreliable due to deviations from the original study design.
Lastly, Health Canada pointed out protocol changes made late in the trial that were not adequately justified, potentially undermining the reliability of the data. AB Science defended these changes as common in large clinical trials and highlighted significant improvements in progression-free survival with masitinib.
In conclusion, Health Canada's decision to reconsider masitinib's approval reflects ongoing efforts to evaluate new treatments for ALS. The process involves careful scrutiny of available data to ensure the safety and efficacy of the medication for patients.
