Another new monoclonal antibody is on the horizon for the treatment of severe asthma. Sanofi and Regeneron’s Dupixent (dupilumab)—which is already approved for atopic dermatitis—has an FDA action date of October 20 for its asthma indication.
About 8% of the general population and 12% of children have asthma. For most people with asthma, the condition can be well controlled with corticosteroids and beta-agonists. But between 5% and 10% have severe cases that resist all control. These people experience acute exacerbations, emergency department visits, and hospital admissions. Sometimes the lungs atrophy. And prolonged use of the oral steroids used to control the disease can cause cataracts or osteoporosis.
Dupixent’s new indication is almost assured, given its existing approval and results from its clinical trials. It will join Nucala, (mepolizumab), Cinqair (reslizumab), and Fasenra (benralizumab) as a monoclonal antibody approved as a treatment for the type 2 inflammation phenotype in severe asthma. This variant of asthma is characterized, in part, by the immune system’s secretion of interleukins-4, -5, and -13 and by activation of eosinophils. High levels of eosinophils are a major cause of the inflammation in severe asthma. The interleukins are signaling molecules that kick off an increase in eosinophils in the airways.
But Dupixent also differs from its MAB cousins: Whereas the others target interleukin-5, Dupixent homes in on IL-4 and IL-13. Patients, rather mysteriously, respond differently to the same medicine, so Dupixent’s unique signaling molecules should make it a welcome addition to the asthma armamentarium.
Its clinical trial results are fairly impressive. The Phase 3 Liberty Asthma QUEST study of 1,902 subjects showed that Dupixent reduces acute exacerbations by almost 50% compared with a placebo. This improvement occurred regardless of eosinophil level. Dupixent also increased the forced expiratory volume in one second (FEV1) measurement by 0.32 liters. But there was also an unanticipated disturbing outcome: Eosinophilia occurred in 4.1% of the Dupixent group compared to 0.6% of those assigned to the placebo.
Competition is heating up among these products. Nucala, a GlaxoSmithKline product, appears to be the current sales leader, probably because it has been on the market the longest (it was approved in 2015). But AstraZeneca, maker of Fasenra, has been especially aggressive about taking on rivals and in anticipation of Dupixent’s asthma indication. According to Reuters, AstraZeneca aims to beat the price of its competitors (payers will be happy if there is some healthy price competition). Fasenra is priced at $38,000 for its initial year of therapy and at $28,000 or $33,000 for subsequent maintenance therapy.
Dupixent is currently priced at $37,000 annually for its dermatitis indication, an increase from its anticipated list price of $30,000. Still, that price would make Dupixent $1,000 cheaper than Fasenra’s first-year price.
As the drug manufacturers duke it out in the marketplace, an editorial in the June 28 issue of the New England Journal of Medicine made an appeal to their altruistic side, calling on them to help researchers sort out the safety and efficacy of the competing agents. The editorial’s authors, Jeffrey Drazen, MD, editor in chief of the Journal, and David Harrington, a professor emeritus at the Harvard T.H. Chan School of Public Health, said the manufacturers have an obligation to suppport head-to-head comparative effectiveness studies by providing their products to investigators at no cost.