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molgramostim (Gramal)

✓ Approved

Probiomed · CSF2RA · Recombinant Proteins

What is molgramostim?

molgramostim is a recombinant proteins developed by Probiomed. It is approved for therapeutic indications via injectable (others).

Drug Profile

Brand NamesGramal
CompanyProbiomed
Drug ClassRecombinant Proteins
Molecular TargetCSF2RA
RouteInjectable (Others)
StatusApproved
Sources: ClinicalTrials.gov, Probiomed

Mechanism of Action

Molecular Targets

molgramostim acts on 1 molecular target:

CSF2RAcolony stimulating factor 2 receptor subunit alpha (CD116, CSF2RX)
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Therapeutic Indications

molgramostim is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Blood and lymphatic system disordersBone marrow disorder✓ Approved

Related Research Articles

PubMedBMC pulmonary medicine2026-02-26

Efficacy of recombinant human GM-CSF compared to placebo for autoimmune pulmonary alveolar proteinosis: a systematic review and meta-analysis.

Naeem Umaimah U, Zahid Hafiza Fatima HF, Imtiaz Sarah S, Khan Quratulain Q et al.

BACKGROUND: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease characterized by surfactant accumulation within alveoli due to impaired clearance or GM-CSF signaling defect. Whole lung lavage (WLL) removes accumulated surfactant but is invasive and does not correct macrophages dysfunction. Recombinant GM-CSF (molgramostim or sargramostim) aims to restore macrophage activity¸ enhance gas exchange and reduce dependence on WLL. OBJECTIVE: This systematic review and meta-analysis evaluated the efficacy of recombinant human GM-CSF (molgramostim or sargramostim) compared with placebo in patients with aPAP. METHOD: Following PRISMA guidelines, PubMed, Cochrane CENTRAL, and Scopus were searched for randomized controlled trials in adults with aPAP receiving molgramostim or sargramostim versus placebo. Primary outcomes included changes in alveolar–arterial oxygen gradient (A-aDO₂) and diffusing capacity of the lung for carbon monoxide (DLCO). Secondary outcomes included St. George’s Respiratory Questionnaire (SGRQ) scores, radiologic ground-glass opacity (GGO) scores, vital capacity, six-minute walk distance, serum biomarkers (CEA and KL-6), and GM-CSF autoantibody levels. Data were analyzed using a random-effects model RevMan 5.4.1, and risk of bias with ROB 2.0. RESULT: Four RCTs involving 338 participants (190 interventions,148 control) were included. Recombinant GM-CSF significantly improved gas exchange, with decreased A-aDO₂ MD of -4.67 (95% CI: -8.49 to -1.42, p = 0.006) and increased DLCO (% predicted) with a mean difference of 6.13 (95% CI: 3.36 to 8.89). Significant improvements were also observed in SGRQ-T scores (MD = –6.60; p < 0.00001) and GGO scores (MD = –1.98; p = 0.0007). No significant differences were found for six-minute walk distance, vital capacity, or serum biomarkers. Most included trials showed low to moderate risk of bias with a few high risk. Egger’s test (p = 0.37) showed no publication bias and overall certainty of evidence ranged from moderate to high. CONCLUSION: Recombinant GM-CSF (molgramostim and sargramostim) is an effective, disease targeted therapy for aPAP. It improves pulmonary function gas exchange and radiological outcomes while reducing reliance on whole lung lavage. TRIAL REGISTRATION: PROSPERO reference number CRD420251165258.

PMID 41742124
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PubMedImmunotherapy2025-10-14

Recombinant GM-CSF drug evaluation review.

McCarthy Jack J, Boyle Niamh N, McCarthy Cormac C

Autoimmune Pulmonary Alveolar Proteinosis (aPAP) is a rare disease characterized by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation, and innate immune deficiency. Pathogenesis is driven by GM-CSF neutralizing autoantibodies (GMAbs) present in high titer in serum and bronchoalveolar lavage fluid (BALF) of patients. GM-CSF is a cytokine and a hematopoietic growth factor produced by a variety of cells. In the lungs, GM-CSF regulates surfactant homeostasis and lung host defense through innate immune function. Whole lung lavage (WLL) is the current first line therapy for aPAP. It is a procedure in which excessive surfactant is mechanically removed from the alveoli. Pathogenesis-driven treatment with GM-CSF augmentation has been investigated over the last two decades with recombinant GM-CSF (rGM-CSF). Molgramostim and sargramostim are rGM-CSF which can be self-administered at home by patients with aPAP either subcutaneously or using a handheld nebulizer. In Phase II and III studies of adults with aPAP, daily administration of inhaled molgramostim resulted in greater improvements in pulmonary gas transfer and functional health status than placebo, with similar rates of adverse events. In all clinical studies to date, rGM-CSF has shown a favorable safety profile with no dose limiting toxicity. This supports the application of inhaled rGM-CSF for the treatment of aPAP and the possibility of WLL as a rescue therapy.

PMID 41085041
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PubMedBMJ open respiratory research2025-09-20

Pharmacokinetics and pharmacodynamics of inhaled molgramostim in healthy people.

Trapnell Bruce C BC, Carey Brenna C BC, Robinson Brian R BR

Inhaled molgramostim, a form of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF), is a promising investigational pharmacotherapy for autoimmune pulmonary alveolar proteinosis (aPAP); however, its pharmacology in healthy subjects has not been reported. This randomised, double-blind, placebo-controlled, single-centre, phase 1 clinical trial assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled molgramostim in healthy adults in single ascending dose (SAD) and multiple ascending dose (MAD) studies: one 150, 300 or 600 µg administration or six consecutive daily 300 or 600 µg administrations with evaluations over 28 or 34 days, respectively. The primary endpoint was safety, which was evaluated based on the number and severity of treatment-emergent AEs following single and multiple inhaled doses of molgramostim. 42 subjects were enrolled including 18 in the SAD study and 24 in the MAD study; all completed the study. Inhaled molgramostim in healthy people was well tolerated and no dose-limiting safety concerns or anti-drug antibody formation were observed in either study. GM-CSF was measurable in serum 30 min after administration of inhaled molgramostim, peaked at 2 hours for all three doses and had an elimination half-life of 1.7±0.0 to 5.9±0.9 hours in the SAD and MAD studies. Systemic GM-CSF exposure was non-linear in both the SAD and MAD studies. Inhaled molgramostim caused a rapid increase in white blood cells (WBC) counts and leucocyte subsets that normalised by 8 hours (SAD) or 15-21 days (MAD). Fractional exhaled nitric oxide remained within the normal range at all doses but was numerically, but not significantly, increased at the 600 μg dose. In healthy people, inhaled molgramostim was well-tolerated and resulted in systemic exposure at picogram levels, which had the expected PD effects on blood leucocyte levels that mostly remained within normal ranges. NCT02468908; EudraCT No. 2013-001687-32.

PMID 40973220
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PubMedDrugs2025-08-28

Pharmacotherapy for Autoimmune Pulmonary Alveolar Proteinosis.

Jouneau Stéphane S, Chauvin Pierre P, Lederlin Mathieu M, Painvin Benoît B et al.

Pulmonary alveolar proteinosis is suspected when a "crazy paving" pattern is observed on a chest CT scan. This diagnosis is confirmed by the presence of eosinophilic extracellular material that shows positive staining with Periodic Acid Schiff on bronchoalveolar lavage samples. The autoimmune form of pulmonary alveolar proteinosis is confirmed by detecting anti-granulocyte-macrophage colony-stimulating factor antibodies in the patient's serum. The historical first-line treatment for autoimmune pulmonary alveolar proteinosis is whole lung lavage, which should only be performed in expert centers. It remains the preferred treatment for patients experiencing respiratory failure, especially at the time of diagnosis. Inhaled granulocyte-macrophage colony-stimulating factor supplementation with molgramostim or sargramostim is now considered a first-line treatment in the international guidelines for autoimmune pulmonary alveolar proteinosis, following the positive results of recent randomized placebo-controlled studies. Rituximab and plasmapheresis can be prescribed as third- and fourth-line treatments, respectively. Lung transplantation may be considered for eligible patients experiencing terminal respiratory failure. A deeper understanding of the pathogenesis of autoimmune pulmonary alveolar proteinosis has opened up new therapeutic avenues, such as the use of PPARγ agonists or statins.

PMID 40866780
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PubMedThe New England journal of medicine2025-08-20

Phase 3 Trial of Inhaled Molgramostim in Autoimmune Pulmonary Alveolar Proteinosis.

Trapnell Bruce C BC, Inoue Yoshikazu Y, Bonella Francesco F, Wang Tisha T et al.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by progressive surfactant accumulation and hypoxemia caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), which alveolar macrophages require to clear surfactant. Molgramostim is a formulation of inhaled recombinant human GM-CSF, but its efficacy and safety in patients with aPAP have not been studied sufficiently. In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with aPAP to receive molgramostim at a dose of 300 μg or placebo once daily for 48 weeks. The primary end point was the change from baseline to week 24 in the diffusing capacity of the lungs for carbon monoxide (DLCO), which was adjusted for hemoglobin concentration and expressed as a percentage of the predicted value. Secondary end points adjusted for multiplicity were the change from baseline in DLCO at 48 weeks and the change from baseline in the St. George's Respiratory Questionnaire total (SGRQ-T) and activity (SGRQ-A) scores (scores range from 0 to 100, with lower scores indicating better quality of life) and in exercise capacity at 24 and 48 weeks. A total of 164 patients underwent randomization: 81 were assigned to receive molgramostim and 83 to receive placebo. The least-squares mean change in DLCO from baseline to week 24 was 9.8 percentage points (95% confidence interval [CI], 7.3 to 12.3) with molgramostim and 3.8 percentage points (95% CI, 1.4 to 6.3) with placebo (estimated treatment difference, 6.0 percentage points; 95% CI, 2.5 to 9.4; P<0.001). The least-squares mean change in DLCO from baseline to week 48 was 11.6 percentage points (95% CI, 8.7 to 14.5) with molgramostim and 4.7 percentage points (95% CI, 1.8 to 7.6) with placebo (P<0.001), and the least-squares mean change in the SGRQ-T score at week 24 was -11.5 points (95% CI, -15.0 to -8.0) and -4.9 points (95% CI, -8.3 to -1.5), respectively (P = 0.007). No significant between-group difference in the change in SGRQ-A score was observed at 24 weeks, so no statistical inference was drawn with respect to subsequent secondary end points. The percentage of patients with at least one adverse event and the percentage with at least one serious adverse event were similar in the two groups. Once-daily inhaled molgramostim led to a greater increase in pulmonary gas transfer than placebo in patients with aPAP. (Funded by Savara; IMPALA-2 ClinicalTrials.gov number, NCT04544293; European Union Clinical Trials Information System number, 2024-511052-41-00.).

PMID 40834301
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PubMedERJ open research2025-03-25

Erratum: "Long-term outcomes in five patients with autoimmune pulmonary alveolar proteinosis treated with molgramostim inhalation solution" Celia Montaño, Elisabeth Bendstrup, Ida Rønnov-Jessen, Sara Salgado, Georg Sterniste, Arschang Valipour, Marcel Veltkamp and Maria Molina-Molina. ERJ Open Res 2024; 11: 00567-2024.

[This corrects the article DOI: 10.1183/23120541.00567-2024.].

PMID 40129543
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