AB Science SA has announced its half-year financial results as of June 30, 2024, and provided an update on its clinical development programs, including masitinib and AB8939.
Masitinib in Amyotrophic Lateral Sclerosis (ALS)
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion on the application for conditional marketing authorization of masitinib in ALS. AB Science has requested a re-examination based on the urgent need for treatment access and the opportunity for review by new rapporteurs and a Scientific Advisory Board.
AB Science acknowledges the challenges in securing conditional marketing authorization for ALS and cannot guarantee a positive outcome. The re-examination will address concerns regarding acceptable masitinib safety, deviations from Good Clinical Practice, exclusion of fast progressors, treatment of missing data, and subgroup data.
Health Canada also issued a Notice of Deficiency-Withdrawal (NOD/w) for the New Drug Submission (NDS) of masitinib in ALS. AB Science has submitted a reconsideration request, which is currently under review with new assessors.
AB8939 in Acute Myeloid Leukemia (AML)
AB Science has updated its AB8939 microtubule program, highlighting its activity against MECOM rearrangement in AML. AB8939, a novel microtubule destabilizer, is in a phase 1 clinical trial (AB18001, NCT05211570) for patients with refractory and relapsed AML.
The phase 1 trial has completed its initial dose-escalation phase and is proceeding to determine the maximum tolerated dose (MTD) following 14 consecutive days of treatment. The next step involves assessing the MTD in combination with Vidaza® (azacitidine).
AB Science reported a complete bone marrow response in an AML patient with MECOM gene rearrangement who had failed prior azacitidine treatment. New data confirm AB8939's activity against MECOM, with a complete response observed in combination with Vidaza in a patient-derived xenograft (PDX) mouse model. In vitro studies showed AB8939 generated a 50% response as a single agent on MECOM cell lines. In the phase 1 trial, 50% of patients with MECOM rearrangement responded to AB8939 as a single agent. The drug appears to be well-tolerated in bone marrow, suggesting potential for long-term treatment.
These findings support the development of AB8939 in a phase 2 clinical trial for MECOM-positive AML, either as a single agent or in combination with Vidaza. AB Science believes a small study may be sufficient for accelerated FDA approval.
Masitinib in Multiple Sclerosis (MS)
Following the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference, AB Science provided an update on masitinib's development in progressive forms of MS. The MAXIMS study (AB20009) is a phase 3 trial evaluating masitinib 4.5 mg/kg/day in primary progressive MS (PPMS) and non-active secondary progressive MS (nSPMS).
Recent tolebrutinib results in nSPMS, presented at ECTRIMS 2024, support the hypothesis of targeting microglia in nSPMS. Tolebrutinib targets microglia via Bruton Tyrosine Kinase (BTK), while masitinib targets microglia via Macrophage Colony Stimulating Factor Receptor-1 (M-CSFR1). Masitinib showed positive results in a phase 2B study (AB07002), consistent with tolebrutinib data.
In study AB07002, masitinib reduced EDSS progression confirmed at 3 months by 37%, compared to a 23% reduction with tolebrutinib in the Hercules study. EDSS progression confirmed at 6 months was reduced by 32% with masitinib and 31% with tolebrutinib. Masitinib also significantly improved manual dexterity, measured by the 9-hole Peg test (-4.28; p=0.0388). Furthermore, masitinib decreased serum neurofilament light chain (NfL) concentration in an animal model of MS, suggesting reduced neuronal damage. Masitinib targets both microglia and mast cells, which play a crucial role in progressive MS and the experimental autoimmune encephalomyelitis (EAE) model.
Masitinib has a large safety database with long-term exposure across various indications. In non-oncology indications, approximately 2,200 patients have received at least one dose of masitinib, with over 1,300 receiving it for more than six months and nearly 1,000 for more than one year. Given the BTK inhibitor safety profiles showing increased liver injury, hypertension, and infections, masitinib represents a potential alternative in both primary and non-active secondary progressive MS.
