Budesonide/Formoterol fumarate/Glycopyrronium Bromide

In a historic first, the FDA on Thursday released about 200 novel and generic drug rejection letters, bucking the agency’s former reticence to publicize the documents in one place. But it’s a small step as nearly all the letters reviewed by Endpoints News were previously disclosed as part of the drugs’ approval packages. Two of the complete response letters not previously disclosed included one for AstraZeneca’s COPD treatment Breztri Aerosphere in 2019 and one for a label update for Astellas’ eye drug Izervay in 2024. All of the rejection letters released are for drugs that have since been approved. AstraZeneca disclosed its CRL in a press release but did not mention that the FDA said the submitted data “do not provide substantial evidence of the efficacy and safety for the use of Breztri Aerosphere.” The CRL also said “the single Aerosphere phase 3 pivotal trial failed on the co-primary endpoint of change from baseline in trough FEV1 for the comparison of Breztri Aerosphere and the glycopyrrolate and formoterol fumarate combination.” AstraZeneca said in a statement to Endpoints that its 2019 press release on the Breztri complete response letter “is an accurate reflection of the status of the regulatory filing and data at the time.” Breztri was later approved in 2020 following submission of additional data. For Izervay’s label expansion, Astellas also announced the CRL in a press release in 2024, but said the FDA comments outlined in the CRL “focus on a statistical matter” and “are unrelated to the safety and benefit/risk of the use of IZERVAY.” The FDA, however, said in the CRL that the company’s proposal to extend the dosing interval “was not supported by the submitted data and was not replicated in a second adequate and well controlled study.” Astellas did not immediately respond to a request for comment. The FDA noted that according to a 2015 analysis conducted by FDA researchers, drug companies “avoided mentioning 85% of the FDA’s concerns about safety and efficacy when announcing publicly that their application was not approved. Moreover, when FDA calls for a new clinical trial for safety or efficacy, that critical information is not disclosed approximately 40% of the time.” The FDA said the CRLs have been redacted for trade secrets and confidential commercial information. It’s unclear if the agency contacted the sponsors prior to releasing the new letters. The agency also said it is in the process of publishing additional CRLs from its archives. “For far too long, drug developers have been playing a guessing game when navigating the FDA,” FDA Commissioner Marty Makary said in a statement. “Drug developers and capital markets alike want predictability. So today we’re one step closer to delivering it to them, with an ultimate goal of bringing cures and meaningful treatments to patients faster.” Editor’s Note: This story was updated with comment from AstraZeneca. An earlier version was updated to reflect a review of the documents released today, finding that some were previously disclosed in approval packages.

The Lung Association is expanding access to the free Lung Health Navigator program. A who’s who of respiratory disease drug developers has backed the American Lung Association’s push to help chronic obstructive pulmonary disease (COPD) patients in rural communities. Sanofi and Regeneron, AstraZeneca, Roche’s Genentech and GSK have provided support for the Living Well with COPD educational campaign. The support will equip the Lung Association to work with rural partners and referral networks, plus local healthcare providers, to deliver services and education to COPD patients.The Lung Association created the campaign for all families across the U.S. affected by COPD, but has paid particular attention to people in rural communities. COPD rates are higher in rural communities than urban areas, the nonprofit said, and patients may lack easy access to hospitals and other resources.  To address the health equity challenge, the Lung Association is expanding access to the free Lung Health Navigator program. The program connects COPD patients to licensed healthcare professionals, either via a phone call, online chat or video meeting. Patients receive free, one-to-one support.  The Lung Association said it is sharing educational materials to help patients “improve communication with their healthcare provider, better understand available COPD treatments and improve their quality of life.” In parallel, the nonprofit is supporting healthcare providers to improve awareness of COPD therapy options.All of the companies that supported the campaign have COPD therapies. Sanofi and Regeneron received FDA approval for Dupixent in the indication last year. The COPD launch got off to a promising start, but the companies’ IL-33 prospect suffered a phase 3 blow in May. Genentech also has an IL-33 candidate. AstraZeneca’s rival IL-33 prospect failed a phase 2 trial last year but development is continuing.AstraZeneca already sells Breztri Aerosphere, an inhaler that competes with GSK’s Trelegy Ellipta for the COPD market. GSK recently won FDA approval for its IL-5 antibody Nucala in COPD. Nucala became the third biologic approved in COPD after Dupixent and Verona Pharma’s Ohtuvayre. Merck & Co. is reportedly closing in on a $10 billion deal to buy Verona.