Masitinib demonstrates potential for severe asthma

The first-in-class oral tyrosine kinase inhibitor (TKI) masitinib demonstrated a positive benefit-risk profile over a sustained period in patients with severe persistent asthma regardless of baseline eosinophil level, with the greatest benefit seen among those with the highest oral corticosteroid (OCS) dependency, according to data presented at ERS 2020.

“[Our study showed a] significant reduction in severe asthma exacerbation rate (SAER) … in the primary analysis population irrespective of baseline eosinophil level [and] in a subgroup of patients with [high] eosinophil levels,” said Prof Pascal Chanez from the University of Aix-Marseille, France in his presentation.

After approximately 60 weeks, annualized SAER was reduced by 35 percent with masitinib vs placebo in the primary analysis cohort (rate ratio [RR], 0.65; p=0.0103) and 38 percent in a subgroup of patients with a baseline eosinophil level of ≥150 cells/μL (RR, 0.62; p=0.0156). [ERS 2020, presentation #4612]

The sensitivity analyses saw a far more pronounced benefit among those who had the most severe asthma. “[These are the] patients who had a higher cumulative use of OCS, [which is] indicative of more severe asthma that is harder to control,” Chanez pointed out.

The SAER reductions in the sensitivity analyses ranged from 41 percent among those with severe asthma (RR, 0.59; p=0.0092 [cumulative OCS >500 mg] and RR, 0.49; p=0.0060 [cumulative OCS >1,000 mg] up to >70 percent among those with severe asthma and high eosinophil levels (RR, 0.51; p=0.0049 and RR, 0.29; p=0.0003, respectively).

Safety-wise, the rates of adverse events (AEs) were similar between the masitinib and the placebo arms among patients reporting ≥1 AE (83 percent vs 82 percent), ≥1 severe AE (48 percent vs 46 percent), and ≥1 serious, nonfatal AE (18 percent vs 16 percent). “Overall, safety was consistent with the known profile for masitinib [with] no new safety signals observed,” said Chanez.

Study AB07015 compared masitinib 6.0 mg/kg/day against placebo in 355 patients with severe asthma uncontrolled by high-dose ICS/LABA* and OCS (≥7.5 mg/day), with no restriction on baseline eosinophil levels. Participants were randomized in a 2:1 ratio. The study comprised a 2-week run-in phase and a 36-week treatment period. A blinded extension phase is planned until week 96.

While there are preclinical and clinical evidence showing the respiratory benefits of masitinib – which is being developed primarily for amyotrophic lateral sclerosis, as well as other neurologic, oncologic, and inflammatory conditions – Chanez noted that the current study population is distinct from other asthma trials. [Int Arch Allergy Immunol 2012;158:369-374; Allergy 2009;64:1194-1201] “[In our study, patients were] dependent on OCS and [did not wean], were treated irrespective of baseline eosinophil count, [and] were evaluated over a long period of time.”

Overall, the findings demonstrate the efficacy of masitinib in a difficult-to-treat population, he said. “[Our findings therefore suggest that] masitinib may provide a new treatment option for biologic-ineligible patients (ie, eosinophil count of ≤300 cells/µL) or those [who have already failed] biologics.”

“In eosinophilic asthma, biologic treatments reduce exacerbation rate by 50–60 percent. [This implies that] there is still an unmet need for more and better treatment options,” said discussant Professor Celeste Michal Porsbjerg from the Bispebjerg Hospital at the University of Copenhagen in Denmark. [ERS 2020, presentation #4615]

“[Given the] lack of effective treatment options for noneosinophilic asthma drugs … this is a very exciting study looking at the effect of an oral TKI,” commented Porsbjerg.