Savara reports exploratory IMPALA trial findings showing numerical improvements in gas transfer, respiratory quality of life and CT lung abnormalities with molgramostim in aPAP patients with preserved diffusion capacity.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Savara Inc. presented post-hoc findings from the Phase 2/3 IMPALA trial at the CHEST 2026 Annual Meeting in Phoenix, Arizona, evaluating inhaled molgramostim in patients with autoimmune pulmonary alveolar proteinosis (aPAP) and relatively preserved diffusion capacity.
The analysis included patients with baseline percent-predicted, hemoglobin-adjusted diffusing capacity of the lungs for carbon monoxide (DLco%) above 70%.
In aPAP, antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) impair alveolar macrophage function, allowing surfactant to accumulate in the lungs. This can interfere with pulmonary gas exchange and impair respiratory health.
Subgroup Selection and Baseline Disease Burden
IMPALA was a randomized, double-blind, placebo-controlled Phase 2/3 trial conducted at 34 sites across 18 countries. Of 138 randomized patients, 13 (9%) had baseline DLco% above 70%. The subgroup analysis included eight patients assigned to continuous once-daily molgramostim 300 µg and three assigned to placebo. Two patients assigned to intermittent molgramostim, administered for seven days every other week, were excluded because the continuous regimen was carried forward into IMPALA-2. Seven molgramostim-treated patients had complete Week 24 data.
Despite relatively preserved diffusion capacity, the subgroup had elevated alveolar–arterial oxygen gradient (A–aDO₂), impaired respiratory health-related quality of life (HRQoL) and substantial radiographic disease burden at baseline.
Gas Transfer Showed the Clearest Numerical Improvement
The primary endpoint was change from baseline to Week 24 in A–aDO₂, a measure of pulmonary gas transfer. Mean A–aDO₂ decreased from 32.5 to 19.8 mmHg with molgramostim, a reduction of 12.7 mmHg. In the placebo group, it decreased from 31.2 to 30.9 mmHg, a reduction of 0.3 mmHg.
Respiratory quality-of-life and imaging measures also changed over 24 weeks.
Measure | Molgramostim | Placebo |
Baseline mean DLco% | 81.9% (range 72.1–97.5%) | 76.9% (range 75.2–78.3%) |
A–aDO₂ change | −12.7 mmHg | −0.3 mmHg |
St. George’s Respiratory Questionnaire (SGRQ) Total change | −7.8 points | −7.2 points |
SGRQ Activity change | −11.1 points | −2.3 points |
CT ground-glass opacity (GGO) score change | −4.9 points | +0.2 points |
Lower SGRQ scores indicate better respiratory HRQoL. The larger numerical reduction in the SGRQ Activity score with molgramostim suggests a potential improvement in activity-related respiratory limitations. However, the SGRQ Total score improved by a similar amount in both groups, making the quality-of-life findings less consistent across measures.
The mean CT GGO score decreased from 8.7 to 3.9 with molgramostim, while it increased from 7.0 to 7.2 with placebo. This change is consistent with a reduction in radiographic lung abnormalities, although GGO is an imaging measure rather than a direct measurement of surfactant concentration.
DLco% was maintained in molgramostim-treated patients, without a reported decline. Given the relatively preserved baseline values, this finding is descriptive and does not establish an improvement in diffusion capacity.
Small Subgroup Limits the Strength of the Evidence
The results require cautious interpretation. The comparison involved only 11 patients: eight assigned to continuous molgramostim and three to placebo. Complete Week 24 data were available for seven molgramostim-treated patients. Savara described the findings as exploratory and hypothesis-generating, without inferential statistical testing for this subgroup.
Consequently, the numerical differences cannot establish a definitive treatment effect. The analysis also cannot determine whether the findings apply to the broader aPAP population or to all patients with relatively preserved diffusion capacity.
Clinical Interpretation
The findings highlight a distinction between diffusion capacity and overall disease burden. A DLco% above 70% did not exclude impaired gas transfer, reduced respiratory quality of life or substantial radiographic abnormalities in this subgroup.
Daily inhaled molgramostim was associated with numerical improvements across gas-transfer, activity-related quality-of-life and CT measures over 24 weeks. The gas-transfer result was the clearest numerical signal, while the quality-of-life findings were mixed.
These observations support further evaluation of disease burden beyond DLco% alone. However, the post-hoc design and very small sample prevent firm conclusions about efficacy in this subgroup. The findings should be considered alongside the broader IMPALA and IMPALA-2 evidence.
Molgramostim remains investigational for aPAP, and its potential role across disease-severity levels depends on the totality of clinical evidence and regulatory assessment.
Reference
Savara Presented New Data Showing Molgramostim Inhalation Solution Treatment Effects in Autoimmune Pulmonary Alveolar Proteinosis Patients with Mild Diffusion Impairment,” Savara Inc. October 21, 2026
Efficacy and Safety of Inhaled Molgramostim (rhGM-CSF) in Autoimmune Pulmonary Alveolar Proteinosis (IMPALA), ClinicalTrials.gov ID NCT02702180
About the Writer
Kirti Kumbhar(LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.