Formoterol Fumarate/Glycopyrrolate

After multiple failed trials of Fasenra in COPD, AstraZeneca will move on to advancing two other biologics—Tezspire and tozorakimab—in the indication. After another swing and a miss for AstraZeneca's Fasenra in chronic obstructive pulmonary disease (COPD), the company is pivoting to other options in its portfolio that might have potential to treat the respiratory condition.In the phase 3 RESOLUTE trial, which included patients with elevated blood eosinophil counts, Fasenra showed numerical improvement in reducing COPD exacerbations but did not reach the statistical significance needed for the study to hit its primary endpoint.The results arrive seven years after Fasenra came up short in two phase 3 COPD trials and 11 years after the IL-5 receptor agonist failed to make the grade in a phase 2a study in the indication.“COPD, which remains a leading cause of death worldwide, is a complex, heterogeneous disease, and we continue to advance other promising approaches in our pipeline to address the unmet needs of patients,” Sharon Barr, who heads up R&D for AZ’s biopharmaceuticals unit, said in a Sept. 17 press release.The company has advanced two other biologics in the indication. Blockbuster asthma treatment Tezspire, a thymic stromal lymphopoietin (TSLP) blocker, is under investigation in two phase 3 trials, while IL-33 tozorakimab is in a phase 3 COPD study that's expected to read out in the first half of 2026. Despite earlier setbacks, AZ had hopes of succeeding with RESOLUTE based on analysis of the results from its prior Fasenra studies in COPD. RESOLUTE included 689 participants with elevated blood eosinophil counts and a history of at least two COPD exacerbations in the year preceding trial enrollment. The participants also were current or former smokers and were on triple-inhaled maintenance therapy.The primary endpoint was the annual rate of moderate or severe COPD exacerbations. Participants remained on their background therapy and received either placebo or 100-mg Fasenra every four weeks for three months, followed by a 100-mg dose every eight weeks. AZ was hoping to compete with other companies, which gained approvals for their biologic treatments in the indication. Sanofi and Regeneron scored a COPD nod for Dupixent in September 2024. Then, four months ago, GSK achieved a similar FDA approval for Nucala.While the results for the trial are “disappointing,” they do not change AZ's peak sales outlook for the brand, which currently stands at a range between $3 billion and $5 billion, a company spokesperson said in an email. Fasenra, which has been on the market for eight years, achieved (PDF) sales of $1.7 billion last year, up by 12% compared to 2023. AZ has a medicine on the market for COPD. Breztri Aerosphere, which was approved as an inhaled maintenance therapy in 2020, generated sales of $972 million last year. The treatment is a combination of the three ingredients included in AZ’s dual-drug regimens Symbicort and Bevespi.AZ’s Saphnelo excels in SubQ studyIt wasn’t all bad news from AZ on Wednesday, as interim results from a phase 3 trial of patients with systemic lupus erythematosus (SLE) showed that subcutaneous (SC) administration of Saphnelo topped placebo. The self-administration format of Saphnelo, which is infused under its current approval, showed a statistically significant and clinically meaningful reduction in disease activity, AZ said in a release. The safety profile of injectable Saphnelo measured up to that seen in previous studies of the drug's intravenous presentation, which was approved in lupus in 2021.The results “provide the opportunity for this important biologic to reach a wider group of patients in a more flexible and convenient way,” said Drexel University's Susan Manzi, M.D., who served as principal investigator on AZ's trial, in the company's announcement. “Despite guidelines recommending earlier intervention and biologic treatments, too many people with systemic lupus erythematosus rely on oral corticosteroids, which contribute to irreversible organ damage.” Results from the trial are under regulatory review and will be presented during the American College of Rheumatology (ACR) annual meeting in October, AZ added.Saphnelo, which generated $304 million in sales in the first half of this year, is projected to achieve peak annual sales of between $1 billion and $3 billion. Future readouts for Saphnelo are on tap in lupus nephritis, systemic sclerosis, myositis and cutaneous lupus erythematosus.