NUCALA autoinjector image from GSK
Chronic obstructive pulmonary disease, a condition CDC estimates affects about 14.2 million (6.5%) U.S. adults, can be brutal. And for patients with COPD, exacerbations are an acute risk, a sudden flare-up where breathing becomes a potentially life-threatening struggle against inflamed airways. “Anecdotally… if I reflect back on some of my experiences in… emergency medicine departments in London, it’s the COPD patients I remember,” said Dr. Kaivan Khavandi, SVP Global Head of Respiratory, Immunology and Inflammation R&D at GSK. Some of the patients are “frequent flyers,” often turning up in the emergency room. “They tend to come in very sick. It’s typically a terrifying experience for junior doctors,” Khavandi said.
In fact, chronic obstructive pulmonary disease is the fourth leading cause of death worldwide, according to WHO. The danger Khavandi describes is concentrated in the aftermath of an exacerbation. In a large national cohort study of first-ever COPD hospitalizations, 22% of patients died within one year of discharge. A review in Respiratory Research noted that studies on mortality following hospitalization related to an acute exacerbation of COPD have shown a one-year mortality from 22% to 43% and a 2-year mortality of 36 to 49%.
Nucala (mepolizumab) approval timeline
November 4, 2015: First FDA approval for severe asthma with an eosinophilic phenotype
December 12, 2017: Approved for eosinophilic granulomatosis with polyangiitis (EGPA/Churg-Strauss Syndrome)
June 6, 2019: Self-administration options approved (prefilled autoinjector and safety syringe)
September 12, 2019: Approved for children aged 6-11 with severe eosinophilic asthma
September 25, 2020: Approved for hypereosinophilic syndrome (HES) – first and only biologic for this indication
July 29, 2021: Approved for chronic rhinosinusitis with nasal polyps (CRSwNP)
January 22, 2022: 40mg prefilled syringe approved for pediatric patients
May 22, 2025: Approved for COPD with eosinophilic phenotype (≥150 cells/μL)
“At the point at which patients are having exacerbations… you’ve got a prognosis that’s comparable to metastatic cancer,” Khavandi said. He argues these events are now “probably more serious today than having a major ST elevation heart attack.” Against this backdrop, the latest FDA approval of GSK’s Nucala as an add-on maintenance therapy for adults with inadequately controlled COPD and an eosinophilic phenotype addresses an unmet need. But for GSK, it is also the opening move in a larger strategy to dismantle the conventional view of COPD and finally bring the precision of modern biologics to a field that has lagged for decades.
At present, Nucala is the only approved biologic for COPD patients with blood eosinophil counts as low as 150 cells/μL – capturing roughly 70% of inadequately controlled COPD patients on triple therapy. This represents over a million potential patients in the U.S. alone.
Nucala’s approval journey
Since its initial FDA approval for severe asthma in November 2015, Nucala has won a string of approvals across IL-5 mediated conditions: from eosinophilic granulomatosis with polyangiitis (2017) to hypereosinophilic syndrome (2020) to chronic rhinosinusitis with nasal polyps (2021).
But for GSK, the latest approval is part of its broader mission of deconstructing COPD. “I think there’s acceptance among pulmonologists and researchers that COPD is a clinical syndrome comprised of lots of different diseases,” he explained. “The ambition is to map pathology where we can say this patient’s disease is driven by IL-33, this one by IL-5, this one by TSLP. We have all those mechanisms in our portfolio.”
Dr. Kaivan Khavandi
This vision of a deconstructed COPD begins by addressing a fundamental challenge in chronic disease: adherence. Nucala’s once-monthly schedule already offers a convenience advantage over its main competitor, Dupixent, which is administered every two weeks for COPD. But GSK intends to push that advantage further. “We also have depemokimab… we’ve disclosed we’re going to develop for COPD,” Khavandi noted. “That’s two injections a year.” He frames this long-acting approach as an enabler of earlier treatment before the disease becomes severe.
This leads to the ultimate goal: redefining COPD treatment by intervening at a much earlier stage. Khavandi acknowledges that to date, all of GSK’s late-stage studies, including MATINEE and METREX, have focused on patients who are already very sick. “They’ve either had one severe exacerbation resulting in hospitalization or two moderate-to-severe requiring oral steroids,” he said. “They’re already at an advanced stage with poor prognosis.”
To break this reactive cycle, Khavandi outlined a shift in strategy. “The aspiration would be: Can we provide solutions that prevent them from even developing an exacerbating phenotype?” he asked. He immediately explained what it would take to make that a reality, noting that to be used in the “pre-biologic segment, it would need properties like depemokimab … and evidence in earlier-stage disease.”
Filed Under: Biologics, Pulmonology
