Benralizumab

iStock, Gearstd The path to market for Roche’s astegolimab became more uncertain after the investigational antibody failed to significantly lower disease exacerbation rates versus placebo in patients with chronic obstructive pulmonary disease. Roche’s quest to establish itself in the biologics market for chronic obstructive pulmonary disease ran into a late-stage roadblock on Monday when its investigational antibody astegolimab failed to elicit significant improvements in patients with the lung disease. Data in Monday’s release were sparse, with the Swiss pharma reporting only that astegolimab given every two weeks lowered annualized exacerbation rate, the study’s primary endpoint, by 14.5% at 52 weeks. The late-stage stumble puts Roche further behind powerhouse competitors Sanofi and Regeneron, which are the clear leaders in the space with Dupixent, approved as the first biologic for COPD in September 2024. Sanofi has previously forecast peak annual COPD sales of $5.5 billion for Dupixent . Roche’s disappointing outcome comes from the Phase III ARNASA trial, which has enrolled some 1,290 patients so far and administered astegolimab every two or every four weeks and compared it against placebo. Roche will report detailed results from ARNASA at an upcoming scientific congress. In the meantime, the pharma will “discuss these data with regulatory authorities to evaluate next steps for astegolimab,” chief medical officer Levi Garraway said in a prepared statement. Administered subcutaneously, astegolimab is a monoclonal antibody targeting the ST2 receptor, preventing binding of the IL-33 ligand and in turn suppressing a signaling cascade that underpins the immune pathways central to the alveolar damage characteristic of COPD. Phase IIa data published in 2022 were likewise underwhelming , with astegolimab failing to significantly lower 48-week exacerbation rate versus placebo. Still, the mid-stage trial suggested improvements in overall health and perceived well-being, leading Roche to start two late-stage studies shortly after: ARNASA in December 2022 and a Phase III open-label extension trial in June 2023. On Monday, Roche also presented Phase IIb data from the ALIENTO trial showing that astegolimab, dosed every two weeks, hit its primary efficacy endpoint, reducing annualized exacerbation rate by 15.4% at 52 weeks. This effect was statistically significant, according to the pharma. In addition to chasing Sanofi and Regeneron’s Dupixent for a piece of the COPD market, Roche also trails GSK, which is looking to expand its asthma drug Nucala into the indication. A Phase III readout in September 2024 found that Nucala significantly lowered annual rates of moderate or severe COPD exacerbations versus placebo. AstraZeneca is also advancing a COPD biologic, though it ran its own setback in 2018, after a Phase III flop forced the pharma to abandon plans to expand Fasenra into the indication. The company is now focusing on its late-stage anti-IL-33 antibody tozorakimab, which is currently in Phase III development for COPD.

AstraZeneca's inhaler Breztri Aerosphere, which was approved for COPD in 2020, has taken a step toward a label expansion as it has aced two asthma trials. AstraZeneca has taken a key step in advancing Breztri Aerosphere toward a potential label expansion and achieving its goal of annual sales of $3 billion to $5 billion for the 3-in-1 inhaler.Two phase 3 trials evaluating the effectiveness and safety of Breztri in a total of 4,434 patients with uncontrolled asthma have met their primary endpoints. The studies showed that Breztri delivered statistically significant and clinically meaningful improvements in lung function compared to dual-drug combinations of inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA) maintenance treatments, AZ said.Data from the KALOS and LOGOS studies will be shared with regulatory authorities and presented at an upcoming medical meeting, the company added.Breztri Aerosphere, which was approved for chronic obstructive pulmonary disorder (COPD) in 2020, is a fixed-dose combination of the corticosteroid budesonide, the LABA formoterol fumarate and the long-acting muscarinic antagonist (LAMA) glycopyrronium.With sales (PDF) of $300 million in the first quarter of 2025, an increase of 37% year over year, Breztri is on its way to blockbuster status for the first time this year.A label expansion to treat asthma would open the treatment up to another large patient population. The condition affects roughly 262 million people around the world, AZ said, with nearly half of those treated with dual therapies remaining uncontrolled. “Despite advancements in asthma treatments, millions of patients remain uncontrolled, which can cause frequent breathlessness, coughing and wheezing,” Alberto Papi, of the St. Anna University Hospital in Ferrara, Italy, said in a press release. “The results from the KALOS and LOGOS trials are exciting and demonstrate the potential of Breztri to evolve the standard of care to more effectively treat asthma in a single inhaled triple therapy.”Breztri was developed as a combination of AZ’s blockbuster Symbicort (budesonide/formoterol), which was approved for asthma in 2006, and Bevespi (formoterol fumarate/glycopyrrolate), which was approved for COPD in 2016. In its development, Breztri has trailed GSK’s triple therapy Trelegy Ellipta, which was approved for COPD in 2017 and for asthma in 2020. Trelegy generated sales of $3.5 billion in 2024, an increase of 26%. GlobalData forecasts that sales of Breztri will reach $2.3 billion in 2030.Breztri is one of several treatments AZ is developing for respiratory diseases, including Fasenra and Amgen-partnered Tezspire. Both of those drugs have been approved to treat asthma and AZ is eying potential COPD label expansions. Fasenra achieved sales of $1.7 billion last year. AZ reported sales for fast-rising Tezspire, which was approved in 2021, at $684 million.