Savara Inc. has submitted a Marketing Authorisation Application (MAA) to the UK Medicines and Healthcare Products Regulatory Agency (MHRA) for Molbreevi (molgramostim inhalation solution), seeking approval for the treatment of autoimmune pulmonary alveolar proteinosis (autoimmune PAP). The MHRA has accepted the application for review, completing a set of parallel regulatory submissions that now spans the US, European Union, and United Kingdom.
The MHRA accepted the MAA under its Accelerated Review pathway, with a 150-day assessment period and a decision expected in Q4 2026, the company said. Molbreevi previously received Innovation Passport and Promising Innovative Medicine designations from the MHRA. In the US, the US FDA is reviewing a Biologics License Application (BLA) under Priority Review, with a PDUFA date of August 22, 2026. The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is also reviewing an MAA, with a decision expected in Q1 2027. Molbreevi holds Breakthrough Therapy, Fast Track, and Orphan Drug designations from the US FDA, and Orphan Drug Designation from the EMA.
The clinical package supporting the submissions draws on two controlled trials. The Phase II/III IMPALA trial (NCT02702180), published in the New England Journal of Medicine in 2020, was a randomized, double-blind, placebo-controlled study measuring change in alveolar–arterial oxygen gradient (A–aDO2) at Week 24. Continuous once-daily inhaled molgramostim produced a mean improvement of −12.8 mmHg versus −6.6 mmHg for placebo, a treatment difference of −6.2 mmHg (P=0.03). The St. George's Respiratory Questionnaire total score also favoured the treatment arm (difference −7.4; P=0.01). Overall adverse event rates were reported as similar across groups, with chest pain occurring more frequently in the molgramostim arm. The IMPALA-2 Phase III trial, reported in abstract form at the 2024 British Thoracic Society meeting, used hemoglobin-adjusted % predicted diffusing capacity of the lungs for carbon monoxide (DLco%) as its primary endpoint. At Week 24, the least-squares mean difference in DLco% change was 6.0% (P=0.0007), extending to 6.9% (95% CI 2.9–10.9) at Week 48. The treatment was described as well tolerated, with most adverse events mild or moderate, though full safety tables have not yet been published.
Autoimmune PAP is a rare chronic lung disease in which neutralizing IgG autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) impair alveolar macrophage function, causing progressive surfactant accumulation in the alveoli. This leads to impaired gas exchange, dyspnoea, cough, and fatigue, with long-term risks including pulmonary fibrosis and the need for lung transplantation. The current standard of care — whole lung lavage — requires general anaesthesia, does not address the underlying immune dysfunction, and must often be repeated as surfactant re-accumulates. Molgramostim, delivered directly to the alveolar space via the proprietary eFlow Nebulizer System (PARI Pharma GmbH), is designed to restore GM-CSF signalling to dysfunctional macrophages, addressing the root pathophysiology rather than providing symptomatic relief alone. If authorized, it would represent the first approved drug therapy for autoimmune PAP globally. Regulatory decisions from the FDA, MHRA, and EMA are all anticipated within the next 12 months.
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