Oral masitinib (AB Science) decreases exacerbations in patients with severe asthma uncontrolled by oral corticosteroids, irrespective of eosinophil count, new research shows.
"This is one of the most unmet needs in asthma patients," said principle investigator Pascal Chanez, MD, PhD, from the University of Aix-Marseille, France.
"For patients without an eosinophilic marker for consistent allergic triggers, there is a huge burden of disease," he told Medscape Medical News. "Currently, the only treatment for them is systemic corticosteroids."
For severe asthma, "we think this drug offers a piece of the treatment puzzle," Chanez said, explaining that severe asthma is a costly chronic disorder that causes disability and hospitalization. What's more, he said he believes masitinib will have good patient adherence because it is an oral medication, "not an injection."
Chanez had been scheduled to present findings from the study on this small-molecule biologic at the American Thoracic Society (ATS) 2020 International Conference this month; instead, a virtual ATS meeting will be held in August.
Masitinib, an oral stem-cell-factor receptor tyrosine kinase inhibitor, targets mast cells and macrophages that are affected in asthma by inhibiting three protein kinases: c-Kit, Lyn, and Fyn.
Chanez and his colleagues assessed 355 patients with severe persistent asthma uncontrolled by an oral corticosteroid dose of at least 5 mg/day and high-dose inhaled corticosteroids or long-acting beta agonists.
In the double-blind randomized trial, 240 participants received masitinib and 115 received placebo for 36 weeks.
The number of severe exacerbations — defined as worsening asthma that required more than a regular maintenance dose of corticosteroids for at least 3 days or hospitalization — was 35% lower in the masitinib group than in the placebo group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 - 0.84; P = .0014).
Adverse-event rates were similar in the masitinib and placebo groups (83.4% vs 82.0%), as were rates of serious adverse events (17.7% vs 16.5%) and severe adverse events (48.0% vs 45.9%).
A subgroup analysis of patients with an initial eosinophil count of at least 150 cells/µL showed a 38% reduction in severe exacerbations in the masitinib group (rate ratio, 0.69; 95% CI, 0.49 - 0.95; P = .0249).
"It's not perfect, but we see far fewer exacerbations," Chanez said. "The next step is to see what happens in real life with patients who may have comorbid conditions."
A Much-Needed Treatment
Masitinib was previously approved for use in dogs as a treatment for mast cell tumors (under the trade name Masivet).
"A drug that works in T2-low — noneosinophilic — asthma is of much interest. It is a critical space without any FDA-approved medications," said Wendy Moore, MD, from Wake Forest School of Medicine in Winston-Salem, North Carolina,
"I am pleased to see immunomodulators that affect effector cells other than eosinophils in phase 3 development," she told Medscape Medical News.
Biologic treatments for asthma have radically changed the landscape, "but only in specific subgroups of patients with severe asthma," she explained. Patients with persistent elevation in blood eosinophils and other biomarkers of T2-high asthma have several new FDA-approved biologic immunomodulators to choose from, such as mepolizumab (Nucala, GSK), benralizumab (Fasenra, AstraZeneca), and dupilumab (Dupixent, Sanofi Genzyme).
But there are many patients who do not qualify for the current FDA-approved drugs. And there are those who are better on a T2 biologic, but still not "fixed", suggesting that there is a mixture of T2-high and T2-low pathobiologic mechanisms at play in those complex patients, who are typically in the sickest group.
However, there is no mention of steroid-sparing or step-down in this trial as there was in trials of mepolizumab and benralizumab. Those trials "showed a 38% decrease in exacerbations in this oral-corticosteroid-dependent group that is reportedly independent of blood eosinophil count," Moore said.
Still, differentiating the effectiveness of biologic drugs is difficult, and not really the point, she added. What's more important is "clearly identifying which drug is the perfect match for the right patient. It's not about which drug is overall better."
The conclusion of Chanez's team — that masitinib significantly reduces the number of asthma exacerbations — "appears to be warranted," said Andy Nish, MD, from the Northeast Georgia Physicians Group in Gainesville, Georgia.
For severe non-type 2 patients with asthma who don't benefit from current treatments, "masitinib may represent a promising new biologic," he added.
The researchers had a relatively large and diverse study population, and defined the study population as at least relatively steroid-nonresponsive, he told Medscape Medical News. "Most asthma studies either look to wean systemic steroids or monitor need for steroid bursts over the course of the study.
By design, this study did not treat allergic or noneosinophilic asthma, and even for the eosinophilic subgroup, a level of "150 eosinophils is not a lot," Nish said.
American Thoracic Society (ATS) 2020 International Conference: Session B93.
Medscape Medical News © 2020
Cite this: Oral Masitinib Improves Severe Asthma - Medscape - May 28, 2020.