Drugs: Studies, Biological Reduces Hospitalizations and Halves Severe Asthma Exacerbations

In adults and adolescents with severe asthma with type 2 inflammation characterized by increased blood eosinophil counts, the ultra-long-acting biologic depemokimab led to a statistically significant and clinically meaningful reduction in exacerbations over 52 weeks, compared with placebo plus standard of care. Given once every 6 months, the drug produced sustained suppression of a key marker of type 2 inflammation, a trigger of asthma attacks and hospital admissions. The data, which refer to the Phase III Swift-1 and Swift-2 clinical trials – according to a note released today by GSK – were presented at the European Respiratory Society International Conference underway until tomorrow in Vienna, Austria, and were simultaneously published in the ‘New England Journal of Medicine’.

Swift-1 and Swift-2 are duplicate studies with the same primary and secondary endpoints. Both met the primary endpoints with statistically significant reductions in the annualized rate of clinically significant exacerbations (asthma attacks) over 52 weeks compared to placebo, with the pre-specified pooled analysis showing a significant 54% reduction in exacerbations. In the pooled analysis, the reduction in clinically significant exacerbations requiring hospitalization or emergency department visits (secondary endpoint) was 72%. In the individual studies, secondary endpoints assessing quality of life or symptom-based measures showed improvements, but did not reach statistical significance compared to placebo.

Prevention of exacerbations, a known risk of hospitalization and a cause of cumulative lung damage and disease progression, has long been a goal of asthma treatment and care for which GSK is focused, the company recalls. Continued suppression of type 2 inflammation, a typical driver of exacerbations, could help change the course of the disease. The possibility of extended dosing intervals could represent an advantage in overcoming barriers such as adherence or frequent medical appointments, in achieving optimal outcomes. “With a dosing schedule of just two injections per year,” said Kaivan Khavandi, SVP, Global Head of Respiratory/Immunology R&D at GSK, “depemokimab has the potential to be the first ultra-long-acting biologic approved with a 6-month dosing schedule. This could offer clinicians and millions of patients with severe asthma an option that provides reassurance of sustained suppression of a key marker of type 2 inflammation over time and a reduction in the rate of exacerbations and hospitalizations, the key treatment goal in asthma.”

Lead author David Jackson, Professor of Respiratory Medicine at King’s College London and Clinical Lead for Severe Asthma at Guy’s and St Thomas’ Hospitals, London, said: “As a clinician, it is encouraging to see research that could evolve the management of severe asthma. For me, preventing exacerbations and particularly those that lead to hospital admissions is a treatment priority for the people I see with severe asthma. Not only are exacerbations traumatic for patients and contribute to pressure on healthcare/hospital systems, 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 harder for the patient to breathe.”

Depemokimab, the first ultra-long-acting biologic to be evaluated in Phase III studies, the note explains, has a high binding affinity and potency for interleukin-5 (IL-5), which will allow for 6-month dosing intervals for patients with severe asthma. IL-5 is a key cytokine (protein) in type 2 inflammation, typically detected by an increase in blood eosinophil counts. More than 80% of people with severe asthma have type 2 inflammation as their underlying pathobiology. Identifying these people could guide clinicians in initiating the correct treatment for their type of asthma, thereby helping to reduce the risk of exacerbations.

The proportion of patients experiencing an adverse event was similar between the depemokimab and placebo groups in Swift-1 (73%) and Swift-2 (72% vs. 78% placebo). No deaths or serious adverse events were related to study treatment. The trial was conducted during a period of high prevalence of Covid and these events were recorded as the most common adverse events. There was no difference in reporting of Covid between those receiving depemokimab or placebo. Nasopharyngitis, another name for the common cold, was the second most common adverse event in the pooled analysis with a lower rate in the depemokimab group than in the placebo group in Swift-1 (12% vs. 10% placebo) and Swift-2 (13% vs. 21%). Safety analysis of the data continues as part of the open-label extension studies.