GSK’s long-acting asthma treatment has been shown to halve the number of attacks in a pair of phase 3 trials, supporting the Big Pharma’s push toward approval despite falling short on some secondary endpoints.
The company had already revealed in May that depemokimab, a monoclonal antibody that blocks human interleukin-5 (IL-5) binding to its receptor, hit the primary endpoint of reducing attacks in the pivotal SWIFT-1 and SWIFT-2 trials. But GSK is only now sharing a look under the hood.
When analyzing data across both studies from 760 adults and adolescents with severe asthma and type 2 inflammation, depemokimab was shown to reduce asthma exacerbations by 54% over 52 weeks when compared to placebo, according to data presented at the European Respiratory Society International Conference in Vienna today.
A pooled analysis also showed a 72% reduction in clinically significant exacerbations that required hospitalization or a visit to an emergency department visit, one of the secondary endpoints across the trials.
However, depemokimab was less successful on other secondary endpoints analyzed individually in the trials, which assessed quality of life, asthma control and how much air a patient can exhale.
On a call to discuss the findings, Kaivan Khavandi, M.D., Ph.D., GSK’s global head of respiratory/immunology R&D, told Fierce Biotech that these secondary fails had been affected by a “significant placebo response, which is obviously an intrinsic challenge with patient-reported outcomes.”
“As a result of that, demonstrating a treatment effect was challenging,” Khavandi said.
When asked by Fierce whether the secondary misses would affect the company’s plans for depemokimab, Khavandi said that it “doesn’t alter the strategy at all.”
“It's well recognized that the most important clinical outcome to prevent is exacerbations,” he added. “And so we already see a paradigm of starting off with the hardest endpoints, which is reduction [of] exacerbations.”
The proportion of adverse events (AEs) was similar between the depemokimab and placebo arms of the studies—73% for both the depemokimab and placebo groups in SWIFT-1, and 72% and 78%, respectively, in SWIFT-2. No deaths or serious AEs were considered to be related to treatment, the company noted.
GSK is continuing to tout depemokimab as one of its 12 potential blockbuster launches of the coming years, with the asthma drug expected to generate peak-year sales of 3 billion pounds sterling ($3.9 billion) if approved.
IL-5 is a known key protein for asthma patients with type 2 inflammation, a condition that elevates levels of a white blood cell called eosinophils. Around 40% of patients taking short- acting biologics for their severe eosinophilic asthma discontinue their treatment within a year, Khavandi noted.
In this context, GSK is banking on depemokimab’s two injections per year setting it up to be the first approved “ultra-long-acting biologic” with six-month dosing.
“Sustained suppression of type 2 inflammation, an underlying driver of these exacerbations, could also help change the course of the disease and so extended dosing intervals can help tackle some of the other barriers to optimal outcomes, such as adherence or frequent healthcare appointments,” Khavandi explained.
On the same call with journalists, Khavandi wouldn’t go into detail about GSK’s time frame for taking depemokimab to regulators but did say that the company will be “immediately advancing to provide the relevant correspondence to the health authorities globally.”
A readout from the late-stage study of depemokimab in chronic rhinosinusitis with nasal polyps is also expected this year, and GSK will be “coordinating our submission strategy” to take account of this, he explained.