Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Inhaled molgramostim, rhGM-CSF, Granulocyte Macrophage-Colony Stimulating Factor (rhGM-CSF)
Molgramostim · 5 trials · 6 indications
Change in Hb-adjusted % predicted DLCO from Baseline.
As a measure of pulmonary gas transfer, a standardized lung function test, DLCO, was conducted. The single-breath DLCO test was performed in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines for DLCO testing. Results reported as % predicted DLCO adjusted for hemoglobin concentration (%predicted DLCOadj).
Sputum culture conversion is defined as at least 3 consecutive sputum samples without growth of NTM during the treatment period.
Measurement of (A-a)DO2 was done by blood gas analysis. An arterial blood sample was collected in the supine position, after resting for at least 10 minutes (or longer if required to achieve stable oxygen saturation). The sample was analyzed for arterial oxygen tension (PaO2) and partial pressure of carbon dioxide (PaCO2). The calculation of (A-a)DO2 was done centrally by using a formula described in the protocol.
| Arm | Type | Description |
|---|---|---|
| molgramostim | EXPERIMENTAL | Molgramostim 300 mcg administered once daily via nebulizer for 48 weeks. |
| Placebo | PLACEBO_COMPARATOR | Double-blind treatment with placebo (PBO) nebulizer solution once daily for 48 weeks |
| Molgramostim Open-label Extension | EXPERIMENTAL | Open-label treatment with molgramostim nebulizer solution 300 µg once daily (Mol OD) for 96 weeks |
| Inhaled molgramostim/antimycobacterials | EXPERIMENTAL | Inhaled molgramostim administered in participants who remain sputum culture positive while currently on a multidrug NTM guideline-based antimycobacterial regimen, which has been ongoing for at least 6 months prior to the Baseline Visit |
| Inhaled molgramostim | EXPERIMENTAL | Inhaled molgramostim administered in participants who remain sputum culture positive but have stopped a multidrug NTM guideline-based antimycobacterial regimen at least 28 days prior to Screening due to lack of response or intolerance, or who never started such treatment |
| Double-blind molgramostim once daily | EXPERIMENTAL | Inhalation of molgramostim nebuliser solution 300 mcg once daily for 24 weeks |
| Double-blind molgramostim intermittent | EXPERIMENTAL | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 weeks (12 cycles) |
| Double-blind placebo | PLACEBO_COMPARATOR | Inhalation of placebo nebuliser solution once daily for 24 weeks |
| Open-label molgramostim intermittent | EXPERIMENTAL | Inhalation of molgramostim nebuliser solution 300 mcg for 7 days and placebo nebuliser solution for 7 days for 24 or 48 weeks from completion of the double-blind period |
| Molgramostim nebuliser solution, inhaled | EXPERIMENTAL | Single dose 150, 300 and 600 ug, multiple dose 300 and 600 ug for 6 days |
| Nebuliser solution, inhaled | PLACEBO_COMPARATOR | Inhaled nebuliser solution |
| Name | Type | Description |
|---|---|---|
| Molgramostim | DRUG | Molgramostim nebulizer solution will be administered once daily using a proprietary nebulizer optimized for the delivery of high molecular weight biologic compounds. |
| Placebo | DRUG | Matching placebo nebulizer solution |
| Molgramostim Open-label | DRUG | Molgramostim 300 µg nebulizer solution |
| Inhaled molgramostim | DRUG | 300 µg / dose molgramostim (recombinant human GM-CSF) for inhalation |
| Antimycobacterial regimen | DRUG | Multidrug NTM guideline-based antimycobacterial regimen |
| PARI eFlow nebulizer system | DEVICE | PARI eFlow nebulizer system |
Inclusion Criteria: * Be ≥6 and \<18 years of age, at the time of signing the informed consent and informed assent (if applicable). * Have a history of pulmonary alveolar proteinosis, based on examination of a lung biopsy, bronchoalveolar lavage cytology, or a high-resolution computed tomogram of t...
Molgramostim is being developed for autoimmune pulmonary alveolar proteinosis (aPAP), a rare lung condition, and has also been studied in non-tuberculous mycobacterial (NTM) infection. It is an inhaled formulation given by nebulizer. Savara, Inc. is pursuing it for aPAP, where it is in late-stage development.
Molgramostim targets GM-CSF, or granulocyte-macrophage colony-stimulating factor. It is a recombinant human GM-CSF, also written rhGM-CSF, delivered directly to the lungs by inhalation. In autoimmune pulmonary alveolar proteinosis, the disease involves neutralizing antibodies against GM-CSF, so restoring GM-CSF signaling in the lung is the therapeutic rationale.
Molgramostim is developed by Savara, Inc., which trades on the Nasdaq under the ticker SVRA. Savara is advancing the inhaled formulation, sometimes called inhaled molgramostim, for autoimmune pulmonary alveolar proteinosis and related lung conditions.
Molgramostim is in the NDA/BLA stage for autoimmune pulmonary alveolar proteinosis, meaning Savara has progressed it to the regulatory submission stage after Phase 3 testing. It is still an investigational therapy and has not been approved. Earlier Phase 2 work covered aPAP and non-tuberculous mycobacterial infection.
Three trials are listed. NCT04544293 is a Phase 3 study in adults with autoimmune pulmonary alveolar proteinosis that is active and not recruiting, with 164 participants. NCT06431776 is a recruiting Phase 3 pediatric aPAP trial in Germany. NCT03421743 was a completed Phase 2 trial in non-tuberculous mycobacterial infection.
Yes. Inhaled molgramostim is the same asset as molgramostim, referring to the nebulized formulation Savara is developing. The trials use the name inhaled molgramostim or inhaled molgramostim nebulizer solution, and the Phase 2 aPAP study is titled with the alternate abbreviation rhGM-CSF, which stands for recombinant human GM-CSF.