There were significantly fewer patients reaching severe dementia stage with masitinib 4.5 mg/kg/day compared with placebo after 24 weeks of treatment.
AB Science announced that its investigational oral agent masitinib met its primary end point in a phase 2b/3 study (AB09004; NCT01872598) in patients with mild and moderate Alzheimer disease (AD).1
Treatment with masitinib 4.5 mg/kg/day (n = 182) generated a significant treatment effect on the primary endpoint of change from baseline in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) compared to those in the control arm (n = 176; P = .0003). AB Science noted that it plans to present the full detailed results at an upcoming meeting.
In addition to the effect on cognition and memory, masitinib 4.5 mg/kg/day generated a significant change from baseline in the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) score, an instrument that assesses self-care and activities of daily living (P = .0381).
"There is a vacuum of treatment options for patients with Alzheimer’s disease and today very few attempts to address the population with confirmed mild or moderate dementia associated with Alzheimer’s disease. These data are very encouraging and may provide new hope for patients with Alzheimer’s disease,” Bruno Dubois, MD, PhD, professor of neurology, Neurological Institute, Salpétrière University Hospital, and coordinating investigator of study AB09004, said in a statement.
Among the notable data points presented, fewer patients who received masitinib 4.5 mg/kg/day reached severe dementia stage (defined as Mini-Mental State Exam [MMSE] <10) compared with placebo after 24 weeks of treatment (P = .0446).
Dubois added, “the fact that masitinib could significantly reduce the proportion of patients reaching the stage of severe dementia is particularly interesting because this stage of the disease represents a significant burden for the society.”
The safety analysis showed that masitinib 4.5 mg/kg/day was acceptable and consistent with its known tolerability profile. In total, 79.5% and 74.6% of patients in the masitinib and control arms, respectively, experienced at least 1 adverse event (AE). Serious AEs, which were non-fatal, were observed in 5.9% of patients in the masitinib arm compared to 2.9% in the control. Incidence of at least 1 serious AE was present in 18.9% of patients in the masitinib arm compared to 16.8% in the control arm.
Study AB09004 was a randomized, placebo-controlled trial that compared the efficacy and safety of masitinib relative to placebo after 24 weeks when administered as an add-on therapy to a cholinesterase inhibitor (donepezil, rivastigmine, or galantamine) and/or memantine. There was a 4.5 mg/kg/day masitinib group along with a 4.5 mg/kg to 6.0 mg/kg/day titrated dose group, each having an independent control arm along with it.
Jeffrey Cummings, MD, ScD, director emeritus, Lou Ruvo Center for Brain Health, Cleveland Clinic, vice chair, Department of Brain Health, University of Nevada-Las Vegas, said in a statement, “The preliminary results from this study support efficacy on important outcomes assessing both cognition and function. The observed patient tolerability is encouraging. Masitinib’s mechanism is novel in its targeting of the innate immune system via mast cells and microglia. A growing body of evidence suggests that microglia play a central role in Alzheimer’s disease and other neurodegenerative disorders.”
Proof of concept for masitinib in AD was established in a 35-patient, double-blind, placebo-controlled phase 2 study. Results from that study showed the rate of clinically relevant cognitive decline, or ADAS-Cog response, was significantly lower with masitinib compared with placebo after 12 and 24 weeks (6% versus 50% for both; P = .040 and P = .046, respectively).2
Patients in the placebo arm also experienced worsening mean ADAS-Cog, ADCS-ADL, and MMSE scores, whereas the masitinib arm reported improvements with statistical significance at weeks 12 and 24.
Masitinib has been evaluated in other neurological disorders such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). In February, AB Science announced that the treatment met its primary end point in a phase 2b/3 study (AB07002) of patients with primary progressive MS (PPMS) and nonactive secondary progressive MS (SPMS).3
In April, the FDA accepted an investigational new drug (IND) application for masitinib, allowing AB Science to proceed with a phase 3 study (AB19001) to test the agent in patients with ALS. The study was intended to confirm results from the first phase 2b/3 AB10015 study (NCT02588677) which demonstrated that masitinib, at 4.5 mg/kg/day in combination with riluzole, significantly slowed decline as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R).4