Dupilumab

A chronic obstructive pulmonary disease approval marks Nucala's fifth in the U.S. While GSK’s Nucala may not have earned the distinction of becoming the first FDA approved biologic for chronic obstructive pulmonary disease (COPD), the British drugmaker is confident its IL-5 antibody still has a major role to play in tackling the traditionally tough-to-treat respiratory condition.Now, following an unexpected delay earlier this month, the company has a fresh FDA green light to put its thesis to the test.The FDA on Thursday approved Nucala as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. The thumbs-up makes Nucala (mepolizumab) the second biologic approved for the disease and the third new COPD therapy to score approval in the U.S. in less than a year.Notably, the FDA approved Sanofi and Regeneron’s immunology juggernaut Dupixent in the indication in September, while Verona Pharma’s Ohtuvayre received the regulatory all-clear last June. Dupixent and Ohtuvayre aren’t in direct competition given that Ohtuvayre is cleared in patients with persistent shortness of breath, while Dupixent is suited for COPD patients with persistent exacerbations.That said, Nucala and Dupixent will likely butt heads in the space following GSK’s launch, given that Dupixent's label covers a similar eosinophil-high patient population.Eosinophils, which are a type of white blood cell, serve as a biomarker for type 2 inflammation and help determine the risk of COPD exacerbations, GSK explained in a release.  COPD—which includes chronic bronchitis and emphysema—is a progressive inflammatory lung disease that causes breathing problems. The condition is one of the leading causes of death in the U.S. alongside heart disease and cancer. While it is mainly caused by smoking, nonsmokers are also susceptible, according to the Centers for Disease Control and Prevention.Inhaled triple therapies have been around to treat COPD for some time, but many patients on those standard-of-care treatments continue to experience persistent symptoms and exacerbations, GSK has said.In turn, the need for additional treatment options remains crucial, Luke Miels, GSK’s chief commercial officer, said on a media call ahead of the FDA’s decision.The GSK exec described patients in Nucala’s phase 3 Matinee study in COPD as being “maxed out" on standard of care. The trial findings suggest the IL-5 antibody can offer patients a “material improvement” while also keeping them out of the hospital, according to Miels.Sizing up the competition Miels figures Nucala will be an enticing option for doctors treating COPD patients given the breadth of the patients who participated in Matinee.GSK’s phase 3 trial recruited COPD patients with chronic bronchitis, emphysema only or both, which can “sometimes be difficult to separate,” Miels said. Conversely, the late-stage trials that supported Dupixent's COPD approval in September included patients who had chronic bronchitis and emphysema or bronchitis alone, but not emphysema only patients, Miels noted.“We had the widest population, which is important because for a physician to stratify these patients, it’s much simpler to be able to say, ‘OK, I can use Nucala in patients whether they’ve got emphysema, chronic bronchitis or both,’” he explained.GSK is also playing up Nucala’s ability to help COPD patients avoid hospitalization, which often marks a severe turn in a person’s prognosis.Around 1 in 4 COPD patients who are hospitalized end up dying within a year, while roughly half of patients who are hospitalized will likely die within five years, Miels said.“There’s a very high burden when you have severe exacerbations and end up being hospitalized,” Miels said. “So, the aim is to keep patients out of the hospital, keep them stable and keep them at home.”In the Matinee study that helped secure Nucala’s approval, the interleukin inhibitor led to a 21% reduction in the annualized rate of moderate or severe COPD exacerbations versus placebo, hitting its primary endpoint, GSK said in a data drop late last month. GSK’s drug also curbed the annualized rate of moderate or severe exacerbations compared to placebo by 31% in patients who only have chronic bronchitis.Nucala also cut patients’ yearly rate of exacerbations leading to emergency room visits and hospitalizations by 35% in one of the trial’s main secondary endpoints, GSK added.The study found that adverse events were largely on par between Nucala and placebo, with the most common issues patients faced including exacerbation or worsening of their COPD.Matinee specifically assessed Nucala in COPD patients with evidence of type 2 inflammation confirmed via high blood eosinophil count. Nucala's approval was also bolstered by older results from the late-stage Metrex study, which pitted the drug against placebo both in COPD patients with an eosinophilic phenotype and those without. While the indication is new territory for Nucala, GSK is no stranger to COPD and currently boasts the “largest product in COPD today” by way of its triple-therapy inhaler Trelegy Ellipta, Miels said. Nevertheless, the company is planning further outreach and education efforts for both doctors and patients in the wake of Nucala’s FDA nod, Miels said.The COPD approval marks the fifth Nucala has received from the FDA, following green lights in severe asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome.Meanwhile, Thursday's approval came two weeks after the FDA missed its original target decision date for Nucala in COPD. GSK had originally expected to hear a verdict on its filing by May 7. On GSK's media call earlier this month, Miels noted that the company plans to “essentially keep the same pricing structure that we already have” with Nucala, which currently costs around $3,800 for a single dose for injection in the U.S. before discounts. The company expects Nucala to hit 500 million pounds sterling (roughly $669 million) in peak year sales for COPD, Miels noted.For all of 2024, Nucala sales across its prior four indications grew (PDF) by 13% at constant currencies to 3.3 billion pounds ($4.4 billion). The drug generated (PDF) 444 million pounds ($594 million) in 2025’s first quarter, a 21% increase over the sum it delivered for the same period last year. 

GSK won a much-anticipated FDA approval for Nucala (mepolizumab) to treat chronic obstructive pulmonary disease (COPD) on Thursday. The green light — which comes more than two weeks past Nucala's PDUFA date — sets the anti–IL-5 antibody up to compete against Sanofi and Regeneron's Dupixent (dupilumab), the dominant player in the space.Specifically, Nucala was cleared as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. GSK decided to focus on patients with a peripheral blood eosinophil count of at least 300 cells/μl after the FDA rejected a broader COPD application in 2018.Dupixent is the first — and only other — biologic therapy approved for COPD, but key opinion leaders (KOLs) who spoke with FirstWord for a recent Therapy Trends report highlighted supporting data for several late-stage programmes, including Nucala, that suggest it could give the dual IL-4/IL-13 inhibitor a run for its money. For more, see Spotlight On: Biologics usher in a new era for COPD.While GSK had reported in September that Nucala significantly lowered the annualised rate of moderate or severe exacerbations in the Phase III MATINEE trial, meeting its primary endpoint, the pharma didn't reveal the specific data behind the study win until just a few weeks ago. A May publication in the NEJM detailed that Nucala reduced the exacerbation rate by 21% versus placebo from baseline through week 104, rising to 31% in patients with clinician-assessed chronic bronchitis. At the time, GSK's Chief Commercial Officer Luke Miels said the results were "very competitive" in comparison to Dupixent.Sanofi and Regeneron's drug was approved for COPD based on results from the BOREAS and NOTUS trials, which demonstrated a 30% and 34% reduction, respectively, in the annualised rate of moderate or severe exacerbations over 52 weeks, compared to placebo."Long-term follow-up studies have demonstrated that exacerbations are the single most important predictor of future risk, with particularly poor outcomes in those requiring hospital visits or admissions," Kaivan Khavandi, GSK's SVP and global head of respiratory, immunology & inflammation R&D, said in a company release. "Today there is hope for improved care for COPD patients with an eosinophilic phenotype."MATINEE also showed that Nucala led to a 35% reduction in the annualised rate of exacerbations leading to emergency department visits and/or hospitalisation versus placebo, a data point that Miels called "critical." However, the company noted that due to the study's statistical design, this secondary endpoint was only "nominally significant after adjustment for multiplicity." For related analysis, see Spotlight On: Can GSK deliver much needed pipeline momentum?Still, the hospitalisation-reduction data was enough to excite US-based pulmonologists surveyed in a recent FirstWord poll who said they were somewhat optimistic about Nucala's potential to carve out some market share away from Dupixent (See — Physician Views Results: GSK's Nucala may rival Dupixent in COPD with hospitalisation benefits).