Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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 an investigational inhaled therapy being studied for autoimmune pulmonary alveolar proteinosis (aPAP) and nontuberculous mycobacterial (NTM) infection. It is developed by Savara, Inc. (NASDAQ: SVRA) and is currently in Phase 3 clinical trials for aPAP.
Molgramostim is a recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) that targets the GM-CSF receptor. It is designed to restore GM-CSF signaling, which is impaired in autoimmune pulmonary alveolar proteinosis, and is administered via inhalation.
Molgramostim is developed by Savara, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol SVRA. The company is conducting Phase 3 clinical trials for the drug in autoimmune pulmonary alveolar proteinosis.
Molgramostim is in Phase 3 clinical development for autoimmune pulmonary alveolar proteinosis. It is not FDA approved and remains investigational. A Phase 3 trial (NCT04544293) is active but not recruiting, and another Phase 3 pediatric trial (NCT06431776) is recruiting.
Molgramostim has been studied in several trials. Completed Phase 2 trials include NCT02702180 in autoimmune pulmonary alveolar proteinosis and NCT03421743 in NTM infection. Active Phase 3 trials include NCT04544293 in aPAP and NCT06431776 in pediatric aPAP.
Molgramostim is a recombinant human GM-CSF, similar in class to sargramostim, but it is a distinct molecule developed by Savara, Inc. It is administered via inhalation for pulmonary conditions, whereas sargramostim is typically given systemically.