Savara's inhaled GM-CSF nears an EU verdict backed by a positive Phase 3 DLCO result
MOLBREEVI's CHMP decision is expected in Q1 2027, arriving after IMPALA-2 already reported a lung-function benefit over placebo, with FDA and MHRA reviews running in parallel.
Executive Summary
- Europe's CHMP is weighing a marketing authorization for an inhaled GM-CSF therapy in a rare lung disease that currently has no approved disease-modifying treatment, with a decision due in the first quarter of 2027.
- The pivotal trial underpinning this filing has already reported its primary lung-function result against placebo, so the European review is acting on a completed dataset rather than awaiting a fresh readout.
- The EU decision follows US and UK filings for the same drug and indication, so the sequence of outcomes across three regulators becomes part of how this event should be read.
- No other program shares this drug, target, and indication in active development, leaving this asset without a validated same-class precedent to benchmark against inside autoimmune PAP.
The catalyst
Savara Inc. said the CHMP is reviewing the MOLBREEVI marketing authorization application for autoimmune PAP, with a decision expected in the first quarter of 2027. The filing sits alongside a US Biologics License Application under FDA Priority Review, carrying an August 22, 2026 PDUFA date, and a UK MHRA application accepted under Accelerated Review with a decision expected in the fourth quarter of 2026. Matt Pauls, Savara's Chair and CEO, said marketing applications for MOLBREEVI "are now being reviewed by regulatory agencies across the U.S., EU, and the U.K., all with decisions expected over the next 12 months". SavaraSavara Announces the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) Has Accepted the MOLBREEVI* Marketing Authorisation Application (MAA) for Autoimmune Pulmonary Alveolar Proteinosis (Autoimmune PAP)Apr 7, 2026
What the trial already showed
The application draws on IMPALA-2 (NCT04544293), a Phase 3, placebo-controlled trial that enrolled 164 patients across 18 countries and is now Active, not recruiting. The trial's primary endpoint measured the change from baseline in percent-predicted diffusing capacity for carbon monoxide (DLCO), a standardized measure of how well the lungs transfer gas into the blood, adjusted for hemoglobin, at week 24, comparing molgramostim against placebo in a double-blind, 48-week treatment period. Results for this outcome, along with a secondary set covering DLCO at week 48, the St. George's Respiratory Questionnaire, and exercise capacity measured in peak metabolic equivalents, were first posted to the trial record on August 7, 2025. Adverse-event reporting from the double-blind period showed 14 of 81 molgramostim-arm participants and 20 of 83 placebo-arm participants experienced a serious adverse event, with no deaths recorded in either arm. NCT04544293Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)NCT04544293
Timeline and enrollment history
The trial's primary completion date moved twice: from November 2023 to June 2024 in June 2021, then back to November 30, 2023 in October 2024, alongside a status change from Recruiting to Active, not recruiting in June 2023. Enrollment grew from a target of 160 to an actual count of 164 alongside the August 2025 results posting, a change under 3%. The overall study completion date runs to May 30, 2027, covering the ongoing open-label extension that has not yet been analyzed. NCT04544293Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)NCT04544293
The competitive field
No other industry sponsor is running a Phase 3 program for a GM-CSF agonist in autoimmune PAP; Savara's only other active trial in the indication is a pediatric study of the same drug, molgramostim, under NCT06431776. Programs elsewhere that touch the GM-CSF Receptor target sit in unrelated indications, including oncology immunotherapy and vaccine combinations, none of which serve as a direct efficacy comparator for autoimmune PAP. Autoimmune PAP has no disease-modifying therapy on the market today; molgramostim's registration would be the first approved treatment to act on the disease's underlying GM-CSF signaling defect rather than on symptom management through whole lung lavage. NCT04544293Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)NCT04544293
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.