Savara Inc. Reports Sustained Efficacy and Favorable Safety Findings from the Ongoing IMPALA-2 Phase 3 Open-Label Extension Study of Molgramostim in aPAP Patients
Savara Inc. announced the presentation of new long-term efficacy and safety findings from its ongoing Phase 3 IMPALA-2 clinical trial evaluating molgramostim for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) during the ATS 2026 International Conference held in Orlando, Florida from May 15-20, 2026. The newly presented data provide additional evidence supporting the durability of response and tolerability profile of molgramostim in patients living with the rare respiratory disease.
The findings were shared in a scientific poster presentation titled “Long-Term Efficacy and Safety of Molgramostim in Patients with Autoimmune Pulmonary Alveolar Proteinosis (aPAP): Results from the IMPALA-2 Trial Open-Label Treatment Period,” presented by Bruce Trapnell. The study is sponsored by Savara and represents one of the largest and longest clinical investigations ever conducted in patients with aPAP, enrolling a total of 164 participants.
Autoimmune pulmonary alveolar proteinosis is a rare lung disease characterized by the abnormal accumulation of surfactant material within the alveoli, the tiny air sacs responsible for gas exchange in the lungs. The condition can significantly impair oxygen transfer, leading to progressive breathing difficulties, reduced exercise tolerance, fatigue, and diminished quality of life. Current treatment options remain limited, creating a substantial unmet medical need for targeted pharmacologic therapies capable of improving lung function and long-term disease management.
Molgramostim is an inhaled recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy designed to address the underlying immune dysfunction associated with aPAP. The therapy is administered through nebulization and is intended to improve pulmonary macrophage function, helping clear accumulated surfactant material from the lungs and restore respiratory function.
According to Savara, the IMPALA-2 trial consists of both a double-blind (DB) treatment period and an extended open-label (OL) treatment phase. During the double-blind portion of the study, patients received either nebulized molgramostim at a daily dose of 300 micrograms or placebo once daily. Specifically, 81 patients were assigned to the molgramostim treatment group while 83 patients received placebo.
Following completion of the double-blind phase, all participating patients were eligible to enter the ongoing 96-week open-label treatment period, during which every patient receives daily molgramostim therapy. The poster presentation at ATS 2026 focused on results from the first 48 weeks of this open-label extension phase.
Savara noted that patient retention throughout the study has remained exceptionally high. Of the 164 patients originally enrolled during the double-blind treatment period, 160 participants, representing approximately 98% of the study population, completed the blinded portion of the trial. All 160 of those patients chose to continue into the open-label extension phase. As of the latest data cutoff, only nine patients had discontinued during the open-label treatment period, resulting in a retention rate of approximately 94%.
Researchers evaluated efficacy primarily through measurements of pulmonary gas transfer using percent predicted diffusing capacity of the lungs for carbon monoxide (DLco%), a key indicator of lung function in aPAP patients. Additional assessments focused on respiratory health-related quality of life using the St. George’s Respiratory Questionnaire Total (SGRQ-T) and Activity (SGRQ-A) scores. Higher SGRQ scores indicate worse respiratory quality of life, meaning reductions in these scores reflect clinical improvement.
The newly presented findings demonstrated that long-term treatment with molgramostim produced sustained improvements in pulmonary gas transfer and respiratory quality of life over time. Importantly, patients who initially received placebo during the double-blind period also experienced meaningful improvements after crossing over to active treatment with molgramostim during the open-label phase.
At the conclusion of the 48-week double-blind treatment period, patients receiving molgramostim demonstrated significantly greater improvements in DLco% compared to patients receiving placebo. The molgramostim treatment group achieved a mean increase from baseline of 11.6, while placebo-treated patients experienced a mean increase of 3.9.
The open-label extension data further demonstrated durability of response among patients who continued molgramostim treatment throughout both study phases, referred to as the MOL-MOL group. These patients continued to show additional gains in pulmonary gas transfer between Weeks 48 and 96, with a mean increase of 2.8 during this period. Overall, the cumulative mean improvement in DLco% from baseline through Week 96 reached 14.7.
Patients who initially received placebo during the double-blind period and later crossed over to molgramostim treatment during the open-label extension, known as the PBO-MOL group, also demonstrated substantial clinical improvement after initiating active therapy. Between Weeks 48 and 96, these crossover patients experienced a mean DLco% increase of 8.8, suggesting that starting molgramostim treatment led to meaningful restoration of pulmonary gas transfer.
The study also reported encouraging long-term improvements in respiratory health-related quality of life measures. During the double-blind phase, patients treated with molgramostim experienced greater reductions in both SGRQ-T and SGRQ-A scores compared with placebo-treated patients, indicating improved respiratory symptoms and daily functioning.
At Week 48 of the double-blind period, mean changes from baseline in SGRQ-T scores were negative 10.8 for molgramostim-treated patients compared with negative 6.1 for placebo-treated participants. Similarly, SGRQ-A scores improved by negative 12.8 in the molgramostim group versus negative 7.8 in the placebo group.
These improvements continued during the open-label extension phase. Patients who remained on continuous molgramostim therapy throughout both phases of the study achieved additional reductions in respiratory quality-of-life scores between Weeks 48 and 96. Overall changes from baseline through Week 96 reached negative 15.0 for SGRQ-T and negative 18.3 for SGRQ-A, demonstrating sustained long-term benefits.
Patients transitioning from placebo to molgramostim treatment during the open-label period also showed clinically meaningful improvements in respiratory quality of life after beginning active therapy. Researchers reported notable reductions in both SGRQ-T and SGRQ-A scores among crossover patients during Weeks 48 through 96.
In addition to efficacy outcomes, investigators presented updated safety and tolerability findings from the open-label treatment period. According to Savara, molgramostim continued to demonstrate a generally favorable safety profile consistent with observations from the earlier double-blind phase of the study. Importantly, no patients discontinued the study due to treatment-related adverse events.
Bruce Trapnell, Professor of Medicine and Pediatrics at the University of Cincinnati College of Medicine and lead clinical investigator of the IMPALA-2 trial, said the long-term data reinforce the therapeutic potential of molgramostim in aPAP patients.
Trapnell noted that patients who received continuous molgramostim treatment demonstrated ongoing improvements in both lung function and quality of life after longer-term drug exposure. He also highlighted that patients who crossed over from placebo to active treatment experienced similar benefits after beginning molgramostim therapy during the open-label period.
According to Trapnell, the consistently high patient retention rate observed throughout the study further supports the long-term tolerability of molgramostim. He stated that the findings are aligned with previous results from the open-label period of the earlier IMPALA study and collectively suggest that prolonged treatment with molgramostim may provide durable clinical benefit for patients with autoimmune pulmonary alveolar proteinosis.
Savara stated that the complete poster presentation will be made available through the Congresses and Publications section of the company’s corporate website. In addition, the abstract has been published in a supplement of the American Journal of Respiratory and Critical Care Medicine.
The new findings presented at ATS 2026 add to the growing body of clinical evidence supporting molgramostim as a potential pharmacologic treatment option for patients with aPAP, a disease area where few approved therapies currently exist. As the IMPALA-2 trial continues, long-term follow-up data may further clarify the role of molgramostim in improving lung function, respiratory symptoms, and overall quality of life in this rare and challenging pulmonary disorder.
Autoimmune PAP is a rare lung disease characterized by the abnormal build-up of surfactant in the alveoli. Surfactant consists of proteins and lipids and is an important physiological substance that lines the alveoli to prevent them from collapsing. In a healthy lung, excess surfactant is cleared and digested by immune cells called alveolar macrophages. Alveolar macrophages need to be stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) to function properly in clearing surfactant, but in aPAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering macrophages unable to adequately clear surfactant.
As a result, an excess of surfactant accumulates in the alveoli, causing impaired gas exchange, resulting in clinical symptoms of shortness of breath, often with cough and frequent fatigue. Patients may also experience episodes of fever, chest pain, or coughing up blood, especially if secondary lung infection develops. In the long term, the disease can lead to serious complications, including lung fibrosis and the need for a lung transplant.
Savara is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, molgramostim inhalation solution (molgramostim) is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (aPAP). Molgramostim is delivered via a proprietary investigational eFlow® Nebulizer System (PARI Pharma GmbH) specifically developed for inhalation of molgramostim. Our management team has significant experience in rare respiratory diseases and pulmonary medicine, identifying unmet needs, and effectively advancing product candidates to approval and commercialization.
