AB Science has announced the launch of a new Phase 3 clinical trial (AB23005) to evaluate masitinib, an oral tyrosine kinase inhibitor, in amyotrophic lateral sclerosis (ALS) patients. The study emerges after regulatory consultation with both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), replacing the previous AB19001 trial that faced recruitment challenges.
Enhanced Trial Design Addresses Previous Limitations
The new study incorporates several key protocol modifications to improve recruitment efficiency and patient accessibility. Unlike its predecessor, AB23005 eliminates the run-in period and broadens inclusion criteria to encompass both moderate and severe ALS patients. Importantly, the trial allows concurrent use of established ALS treatments, including Radicava (edaravone) and riluzole-based therapies.
The company projects ambitious timeline goals, anticipating complete enrollment within one year and study completion within two years. The trial will recruit 408 participants with normally progressing disease, defined by maintaining minimum functionality across all areas measured by the ALS Functional Rating Scale-Revised (ALSFRS-R).
Strong Foundation from Previous Clinical Evidence
The decision to proceed with a new Phase 3 trial is supported by encouraging results from an earlier Phase 2/3 study (NCT02588677). In that trial, masitinib demonstrated significant therapeutic potential, particularly at the 4.5 mg/kg daily dose, showing:
- 27% reduction in disease progression compared to placebo
- Approximately one-year survival benefit in patients with mild to moderate disease
- Promising long-term outcomes in compassionate use programs
Trial Design and Objectives
AB23005 will evaluate masitinib at the 4.5 mg/kg dose against placebo over a 48-week treatment period, followed by an open-label extension phase. The study's primary endpoints include:
- Combined Assessment of Function and Survival (CAFS)
- Changes in ALSFRS-R scores
Secondary assessments will track quality of life metrics, survival data, and disease biomarkers. Meanwhile, the original AB19001 trial will be repurposed as a supportive study to investigate the safety and efficacy of a higher 6 mg/kg dose.
Scientific Rationale and Mechanism
Masitinib functions by inhibiting tyrosine kinases, enzymes crucial for immune cell function that are implicated in ALS-related inflammation and neuronal damage. The drug's mechanism suggests potential to moderate inflammatory responses and potentially slow disease progression in ALS patients.
This strategic pivot in clinical development follows regulatory feedback after previous conditional approval applications in the European Union and Canada. While these applications received negative opinions, regulators supported the pursuit of a confirmatory Phase 3 study focused on patient populations most likely to benefit from masitinib treatment.
