Molgramostim

Cytokine (granulocyte Macrophage Colony Stimulating Factor)Rx: InvestigationalCompound: Investigational

Also known as: CSF2 recombinant, GM-CSF, Leucomax, Molgradex, recombinant human GM‑CSF, rhGM‑CSF, rhu GM-CSF (E. coli)

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Source Molgramostim at Peptiology

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Summary

Molgramostim is a recombinant human granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) investigated for therapeutic use. The principal clinical focus is autoimmune pulmonary alveolar proteinosis (aPAP), a rare lung disorder where neutralising antibodies impair surfactant clearance. Inhaled molgramostim is being evaluated as a disease‑modifying, home‑administered therapy, and it has also been studied as an adjunct to antibiotics in abdominal sepsis.

Mechanism of Action

Molgramostim mimics endogenous GM‑CSF and binds the heterodimeric CSF2 receptor (α‑chain CD116 and common β‑chain). Ligand engagement activates JAK2, leading to STAT5 phosphorylation and transcription of genes that promote differentiation, survival and activation of alveolar macrophages and neutrophils. In the lung, restored macrophage function enhances surfactant catabolism, while systemic effects increase white‑blood‑cell counts, supporting innate immunity.

What the Research Shows

Randomised, double‑blind trials have examined inhaled molgramostim in aPAP. The phase 3 IMPALA‑2 study (164 patients) showed a 6‑percentage‑point greater improvement in DLCO at 24 weeks versus placebo (P<0.001) and a clinically meaningful reduction in St George's Respiratory Questionnaire total score, with adverse‑event rates comparable to placebo. Earlier phase 2 data (2020) demonstrated superior improvement in alveolar‑arterial oxygen difference and quality‑of‑life scores, though chest pain was more frequent with continuous dosing. A phase 1 PK/PD study in healthy volunteers reported dose‑related, transient leukocytosis and no anti‑drug antibodies, confirming tolerability. A single trial in abdominal sepsis (58 patients) found molgramostim plus antibiotics shortened time to improvement, reduced hospital stay and infectious complications versus placebo. A 2025 review summarised these findings, noting a favourable safety profile across studies.

Reported Benefits

In aPAP, inhaled molgramostim consistently improves gas‑transfer measures (DLCO, A‑aDO2) and patient‑reported health status, with effect sizes exceeding minimal clinically important differences. The phase 3 trial reported a 9.8‑point rise in DLCO versus 3.8 points with placebo, and a 11.5‑point drop in SGRQ total score versus 4.9 points. In abdominal sepsis, adjunctive molgramostim accelerated clinical improvement (median 2 vs 4 days), shortened hospitalization (median 9 vs 13 days) and lowered infectious complications. Across trials, overall adverse‑event frequencies were similar to control groups.

Limitations of the Evidence

Evidence is limited to relatively small, disease‑specific trials; long‑term outcomes and durability of response remain unclear. The aPAP studies enrolled fewer than 200 participants each and focused on 24–48‑week endpoints. Data on intravenous or subcutaneous administration are confined to early‑phase or non‑pulmonary studies, preventing direct comparison with inhaled delivery. The sepsis trial was a single‑center study from 2006, and its findings have not been replicated. No head‑to‑head comparisons with other GM‑CSF products or with whole‑lung lavage exist, and regulatory approval has not been granted.

Safety Considerations

Molgramostim was well tolerated in both healthy volunteers and patients. The most common treatment‑emergent events were mild, transient increases in white‑blood‑cell counts that returned to baseline within hours to days. In the phase 3 aPAP trial, the proportion of participants experiencing any adverse event or a serious adverse event was similar to placebo; chest pain occurred more frequently with continuous inhalation in the earlier trial. No dose‑limiting toxicities, anti‑drug antibodies, or unexpected laboratory abnormalities were reported in the PK/PD study. Overall, the safety profile appears comparable to placebo over the studied durations.

How It Is Administered

Molgramostim is supplied as a recombinant protein for inhalation, typically delivered via a handheld nebuliser at a dose of 300 µg once daily in aPAP trials. Intravenous and subcutaneous routes have been used in early‑phase research but are not standard clinical formulations. The drug is stored as a lyophilised powder reconstituted before nebulisation; dosing schedules may vary in investigational protocols.

Routes of Administration

InhalationInhaledIntravenousSubcutaneous

Goals & Uses

  • Pulmonary alveolar proteinosisRespiratoryModerate
  • Treatment of aplastic anemiaHematologyLow
  • Bone marrow transplant supportHematology/OncologyModerate
  • Chemotherapy‑induced neutropeniaHematologyModerate
  • Treatment of chemotherapy-induced neutropeniaHematologyHigh
  • Infectious disease adjunct (COVID-19)Infectious DiseaseLow
  • Acute Respiratory Distress Syndrome (ARDS)RespiratoryLow
  • Treatment of autoimmune pulmonary alveolar proteinosis (aPAP)PulmonologyModerate

Contraindications

  • Concurrent myeloid malignancyOncologyHigh
  • Known hypersensitivity to molgramostim or any excipientAllergyHigh
  • Hypersensitivity to GM-CSF or E. coli-derived proteinsAllergy/ImmunologyHigh
  • Active autoimmune conditions (non-PAP) without monitoringImmunologyModerate
  • Excessive myeloid blast count (>10%) or leukemiaOncologyHigh
  • Active myeloid malignancy (e.g., AML)OncologyModerate

Adverse Effects

  • Bone painMusculoskeletalCommon
  • Fever and flu-like symptomsConstitutionalCommon
  • Cough/bronchospasm (inhaled route)PulmonaryCommon
  • Injection site reactionsLocalCommon
  • Capillary leak syndromeVascularRareLeakage of fluid from blood vessels into tissues
  • Pleural/pericardial effusionCardiovascular/PulmonaryUncommon
  • FeverSystemicCommonElevated body temperature
  • Injection‑site reactionLocalCommon
  • Bone pain / musculoskeletal painMusculoskeletalCommon

Drug Interactions

  • Other myeloid growth factors (e.g., filgrastim)Low
  • Myelosuppressive chemotherapy agentsModerate
  • CorticosteroidsModerate
  • LithiumLow

Population Constraints

  • PregnancyReproductive SafetyRelative
  • Pediatric patientsAgeRelative
  • Pediatric patients (<1 year)AgeRelative
  • Pregnant womenReproductiveRelative
  • Patients with autoimmune disease historyImmunologyRelative
  • Renal or hepatic impairmentOrgan DysfunctionRelative

Regulatory Status

  • European UnionInvestigationalEMA has not granted marketing authorization.
  • United StatesInvestigationalNot FDA‑approved; used in clinical trials.
  • United KingdomInvestigationalMHRA classifies as Clinical Trial Material.

Approved in some European and other countries historically for chemotherapy-induced neutropenia; sargramostim (yeast-derived, glycosylated) is the FDA-approved GM-CSF in the US. Molgramostim (inhaled) is under active investigation in the EU and US for autoimmune pulmonary alveolar proteinosis (IMPALA trials).

Evidence & Sources

Frequently Asked Questions

What condition is molgramostim being studied for?

The primary indication under investigation is autoimmune pulmonary alveolar proteinosis, a rare disease in which antibodies block GM‑CSF activity and impair surfactant clearance. It has also been evaluated as an adjunct in abdominal sepsis.

How is molgramostim administered?

In clinical studies for aPAP, molgramostim is inhaled using a nebuliser, usually 300 µg once daily. Intravenous and subcutaneous routes have been explored in early‑phase trials but are not part of the current standard protocol.

What benefits have been demonstrated?

Randomised trials have shown that inhaled molgramostim improves lung gas‑transfer (DLCO, A‑aDO2), reduces dyspnoea scores, and enhances quality‑of‑life measures in aPAP. In a sepsis study, it shortened time to clinical improvement and reduced hospital stay.

What side effects should be expected?

The safety record is comparable to placebo. Common observations include transient rises in white‑blood‑cell counts and, in one study, a higher incidence of chest pain with continuous dosing. No dose‑limiting toxicity or anti‑drug antibodies have been reported.

Is molgramostim approved for clinical use?

Molgramostim remains an investigational, prescription‑only product. It has not received regulatory approval for any indication, and its use is confined to clinical trials and research settings.

What is Molgramostim?

Molgramostim is a recombinant human granulocyte‑macrophage colony‑stimulating factor (GM‑CSF) investigated for therapeutic use. The principal clinical focus is autoimmune pulmonary alveolar proteinosis (aPAP), a rare lung disorder where neutralising antibodies impair surfactant clearance. Inhaled molgramostim is being evaluated as a disease‑modifying, home‑administered therapy, and it has also been studied as an adjunct to antibiotics in abdominal sepsis.

What is Molgramostim used for?

Molgramostim is educationally associated with: Pulmonary alveolar proteinosis, Treatment of aplastic anemia, Bone marrow transplant support, Chemotherapy‑induced neutropenia, Treatment of chemotherapy-induced neutropenia, Infectious disease adjunct (COVID-19), Acute Respiratory Distress Syndrome (ARDS), Treatment of autoimmune pulmonary alveolar proteinosis (aPAP). Educational only — not medical advice.

How is Molgramostim administered?

Recorded routes of administration: Inhalation, Inhaled, Intravenous, Subcutaneous.

What are the potential side effects of Molgramostim?

Reported adverse effects include: Bone pain, Fever and flu-like symptoms, Cough/bronchospasm (inhaled route), Injection site reactions, Capillary leak syndrome, Pleural/pericardial effusion, Fever, Injection‑site reaction, Bone pain / musculoskeletal pain. This list is not exhaustive — consult a qualified clinician.

Who should avoid Molgramostim?

Recorded contraindications: Concurrent myeloid malignancy, Known hypersensitivity to molgramostim or any excipient, Hypersensitivity to GM-CSF or E. coli-derived proteins, Active autoimmune conditions (non-PAP) without monitoring, Excessive myeloid blast count (>10%) or leukemia, Active myeloid malignancy (e.g., AML). Consult a qualified clinician before use.

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