Severe asthma is a debilitating form of this respiratory disease that requires intensive treatment with high doses of inhaled corticosteroids combined with other controllers or biologic therapies. Despite these efforts, in many cases it remains difficult to control. In most patients with severe asthma, the disease is driven by type 2 inflammation, characterized by high levels of eosinophils, a type of white blood cell, whose activity is regulated by proteins such as IL-5, IL-4, and IL-13. These cytokines play a central role in the inflammation associated with a variety of immunological conditions.
This type of asthma, which affects a significant minority of patients, carries a disproportionate economic impact: it accounts for more than 60% of asthma-related costs in some countries and generates higher per-patient costs than other chronic diseases such as type 2 diabetes or stroke. The economic burden includes not only direct medical costs, but also loss of income due to frequent exacerbations leading to sick leave or even hospitalisation.
At the recent European Respiratory Society Congress (7-11 September in Vienna, Austria), GSK has presented the full results of the Phase III SWIFT-1 and SWIFT-2 clinical trials evaluating the potential of depemokimab as a treatment for severe asthma with type 2 inflammation, a form of the disease characterised by high levels of eosinophils in the blood. Both studies, whose results have been published in parallel in the New England Journal of Medicine, followed patients for 52 weeks, meeting their primary endpoints by demonstrating a significant reduction in the rate of severe exacerbations (asthma attacks). Compared with placebo, depemokimab managed to reduce these exacerbations by 54% (rate of 0.51 exacerbations per year versus 1.11 with placebo, p<0.001).
A pooled analysis of the two trials found that depemokimab also reduced the number of exacerbations requiring hospitalisation or an emergency department visit by 72% (0.02 exacerbations per year vs 0.09 with placebo, p=0.002). This nominally significant reduction indicates a considerable impact in preventing serious asthma complications. However, it is important to note that some secondary endpoints, such as improvements in quality of life and symptom reduction, did not reach statistical significance in the individual trials.
These results advance the investigation of targeted treatments for patients with severe asthma, with the aim of preventing exacerbations, which are a known risk factor for hospitalization and cumulative lung damage. In the long term, sustained suppression of type 2 inflammation could alter the course of the disease and reduce progression. In addition, the extended dosing intervals offered by depemokimab could improve treatment adherence, alleviating the burden of frequent medical visits and optimizing outcomes for patients.
“With a dosing schedule of just two annual injections, depemokimab has the potential to be the first ultra-long-acting biologic approved with six-month dosing, offering physicians and millions of patients with severe asthma an option that provides the reassurance of sustained suppression of a key marker of type 2 inflammation and reduced rates of exacerbations and hospitalizations – key goals in asthma treatment,” said Kaivan Khavandi, Senior Vice President and Global Head of R&D, Respiratory & Immunology.
David Jackson, lead author of the SWIFT-1 and SWIFT-2 studies, Professor of Respiratory Medicine at King’s College London and Clinical Director for Severe Asthma at Guy’s and St Thomas’ Hospitals in London, commented: “As a clinician, it is encouraging to see research findings that could evolve the treatment of severe asthma. For me, preventing exacerbations and in particular those that lead to hospitalisation is a treatment priority for the people I see with severe asthma. Not only are exacerbations traumatic for patients and contribute to pressures on healthcare systems and hospitals, but each exacerbation can cause irreversible changes to lung tissue that over time can lead to permanent loss of lung function and make it progressively more difficult for a patient to breathe.”
This is how this ultra-long-acting biological drug works against asthma
Depemokimab has become the first ultra-long-acting biological treatment evaluated in phase III clinical trials for severe asthma. This drug stands out for its high affinity and binding potency to interleukin-5 (IL-5), a key cytokine in type 2 inflammation, present in more than 80% of patients with severe asthma. Thanks to this ability to block IL-5, depemokimab will allow a dosing interval of up to six months, which could represent an important advance in treatment adherence and the reduction of exacerbations. Type 2 inflammation, identified by an elevated blood eosinophil count, is the underlying pathobiology in most cases of severe asthma, which means that early detection of this condition allows for more appropriate management of the disease.
Thanks to this ability to block IL-5, depemokimab will allow a dosing interval of up to six months, which could represent an important advance in treatment adherence and the reduction of exacerbations.
The SWIFT-1 and SWIFT-2 trials, conducted during a period of high prevalence of COVID-19, demonstrated comparable safety between patients treated with depemokimab and those receiving placebo. In SWIFT-1, 73% of patients in both groups reported an adverse event (AE), while in SWIFT-2 the proportion was 72% in the depemokimab group versus 78% in the placebo group. The most common adverse events were COVID-19 infections (20% in depemokimab vs. 22% in placebo in SWIFT-1; 15% in both groups in SWIFT-2), followed by nasopharyngitis, more commonly known as the common cold. Nasopharyngitis was reported at a lower rate in the depemokimab group (12% vs. 19% in placebo in SWIFT-1; 13% vs. 21% in placebo in SWIFT-2).
These studies not only showed good tolerability of the treatment, with no deaths or serious adverse events related to the drug, but will also serve as a basis for future regulatory applications around the world. Although depemokimab has not yet been approved in any country, the results of these trials open the door to a more effective and convenient treatment for patients with severe asthma, who could benefit from longer dosing intervals and greater stability in the control of their disease.
Source: GSK
