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May 20, 2026

C104-03 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

Key Points

To assess the long-term efficacy and safety of Molgramostim in patients with autoimmune pulmonary alveolar proteinosis (aPAP).
Randomized, double-blind, placebo-controlled phase 3 trial with a 48-week double-blind period followed by a 96-week open-label period.
Patients received inhaled Molgramostim (300 µg) or placebo during the double-blind period; all received Molgramostim during the open-label period.
Efficacy assessed via changes in diffusing capacity of the lungs for carbon monoxide (DLco%) and St. George’s Respiratory Questionnaire scores.
Mean increase in DLco% was 11.6 for the Molgramostim group and 3.7 for the placebo group at Week 48 (P = 0.0008).
Patients receiving Molgramostim throughout showed an overall DLco% increase of 14.7 from baseline (Weeks 0-96).
During the open-label period, SGRQ-T scores decreased by -15.0 and SGRQ-A scores decreased by -18.3 for the Molgramostim-Molgramostim group.

Abstract

Abstract Rationale aPAP is a rare chronic lung disease caused by autoantibodies blocking granulocyte-macrophage colony stimulating factor (GM-CSF) signaling, resulting in alveolar macrophage dysfunction and surfactant accumulation. Molgramostim inhalation solution (MOL) is a recombinant human GM-CSF in development as a pharmacotherapy for aPAP. IMPALA-2 is a randomized, double-blind, placebo-controlled phase 3 trial comprising a 48-week double-blind treatment (DB) period (completed) followed by a 96-week open-label treatment (OL) period (ongoing) to assess the long-term efficacy and safety of MOL. Here we report results from the first 48 weeks of the 96-week OL period. Methods Patients with aPAP were randomized to receive inhaled MOL (300 µg) or placebo (PBO) once daily during the DB period; all patients received MOL during the OL period. Efficacy was assessed by change from baseline in percent predicted diffusing capacity of the lungs for carbon monoxide (DLco%) and by St. George’s Respiratory Questionnaire Total (SGRQ-T) and Activity (SGRQ-A) Scores assessing respiratory health-related quality of life (HRQoL). Results Of 164 patients with aPAP receiving MOL (n = 81) or PBO (n = 83) during the DB period, 160 (98%) completed the DB period and continued into the OL period. At Week 48, the mean (standard error) changes from baseline in DLco% were 11.6 (1.4) for the MOL group and 3.7 (1.5) for the PBO group; the difference in least-squares mean changes between the MOL and PBO groups was 6.9 (P = 0.0008). During the OL period, patients receiving MOL during both DB and OL periods (MOL-MOL) continued to show improvement in DLco% through Week 96; the mean increase during Weeks 48-96 was 2.8 (1.2) with an overall increase from baseline (Weeks 0-96) of 14.7 (1.6) (Figure). In PBO patients crossing over to MOL in the OL period (PBO-MOL), DLco% increased during the OL treatment period through Week 96; the mean increase in DLco% during Weeks 48-96 was 8.8 (1.6). For SGRQ-T and SGRQ-A scores during the OL period, the MOL-MOL group showed continued improvement during Weeks 48-96 with mean decreases of -3.8 (1.6) and -4.2 (2.5) (SGRQ-T and SGRQ-A), and overall decreases from baseline (Weeks 0-96) of -15.0 (2.6) and -18.3 (3.5). In PBO-MOL, corresponding decreases were -6.5 (1.6) and -7.9 (2.0) during Weeks 48-96. Safety and tolerability were consistent with the DB period. Conclusions Long-term treatment with MOL continuously improved pulmonary gas transfer and respiratory HRQoL in patients with aPAP. In addition, PBO cross-over patients demonstrated improved pulmonary gas transfer and respiratory HRQoL. This abstract is funded by: Savara Inc.

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