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Release
Savara Announces Molgramostim Nebulizer Solution (Molgramostim) Achieved Statistical Significance for Primary Endpoint and Multiple Secondary Endpoints in IMPALA-2, a Pivotal Phase 3 Clinical Trial in Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
- Statistically Significant Improvement in Percent Predicted Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Versus Placebo at Week 24 (Primary Endpoint) and Week 48 (Secondary Endpoint)
- Statistically Significant Improvement in St. George’s Respiratory Questionnaire (SGRQ) Total Score at Week 24 (Secondary Endpoint)
- 97% of Patients Completed Double-Blind Treatment Through Week 48 with No Trial Drug Related Adverse Events Leading to Discontinuation
- 100% of Patients Completing the 48-Week Double-Blind Period Elected to Participate in the 96-Week Open-Label Period
- Company Plans to Complete BLA Submission in 1H 2025
-
Company to Host Webcast Conference Call Today,
June 26, 2024 at8:00am ET
The trial met its primary endpoint. The treatment difference between molgramostim and placebo for mean change from baseline to Week 24 in hemoglobin-adjusted percent predicted DLCO achieved statistical significance. This statistically significant treatment difference was sustained at Week 48, a secondary endpoint, which demonstrated durability of effect.
The treatment difference between molgramostim and placebo for mean change from baseline to Week 24 in SGRQ Total Score achieved statistical significance. Two additional secondary endpoints reached nominal significance: SGRQ Activity Score at Week 24 and exercise capacity using a treadmill test at Week 48.
“There is a high unmet need for effective, disease-specific pharmacotherapy for autoimmune PAP,” said
IMPALA-2 Top Line Efficacy Results (Full Analysis Set, n=164):
Lung Function Efficacy Endpoints | ||||
Molgramostim 300 mcg mean change from baseline compared to placebo |
P-value | |||
Primary: DLCO % predicted (Hgb-adjusted) at Week 24 |
6.00 |
0.0007 |
||
Secondary: DLCO % predicted (Hgb-adjusted) at Week 48 |
6.90 |
0.0008 |
||
Secondary Efficacy Endpoints Measuring Clinical Benefit | ||||
Molgramostim 300 mcg mean change from baseline to Week 24 compared to placebo |
P-value | Molgramostim 300 mcg mean change from baseline to Week 48 compared to placebo |
P-value | |
SGRQ Total Score (points) |
-6.59 |
0.0072 |
-4.87 |
0.1046 |
SGRQ Activity Score (points) |
-7.81 |
0.0149 |
-5.99 |
0.1216 |
Exercise Capacity (peak METs) |
0.41 |
0.0845 |
0.55 |
0.0234 |
SGRQ is a patient-reported outcomes instrument that measures overall health, daily life, and a patient’s perceived well-being. SGRQ Activity assesses the patient’s ability to carry out daily physical activity. With SGRQ, a negative change from baseline corresponds to improvement. Exercise capacity as measured by a treadmill is a cardiorespiratory health (CRH) measurement. |
Molgramostim was well tolerated. The frequency of adverse events was generally similar between treatment groups. Two patients (2.5%) discontinued molgramostim treatment due to adverse events, both of which were considered unrelated to trial drug. The most commonly reported adverse events in the molgramostim group were COVID-19, cough, and pyrexia, with COVID-19 occurring more frequently with molgramostim than with placebo.
IMPALA-2 Top Line Safety Results (Safety Analysis Set, n=164):
Treatment Related Adverse Events | Molgramostim (N=81) n (%) |
Placebo (N=83) n (%) |
Any |
69 (85) |
71 (86) |
Most common |
||
COVID-19 |
18 (22) |
8 (10) |
Cough |
17 (21) |
18 (22) |
Pyrexia |
11 (14) |
9 (11) |
Nasopharyngitis |
11 (14) |
7 (8) |
Arthralgia |
9 (11) |
7 (8) |
Headache |
9 (11) |
7 (8) |
Diarrhea |
9 (11) |
2 (2) |
Alveolar proteinosis |
4 (5) |
12 (14) |
Serious |
14 (17) |
20 (24) |
Treatment related |
20 (25) |
16 (19) |
“The IMPALA-2 results not only met, but exceeded, our expectations, validating our hypothesis that molgramostim provides clear, durable improvement in gas exchange, and beyond that, clinical benefits that positively impact quality of life for aPAP patients," said
Molgramostim has been granted Orphan Drug, Fast Track, and Breakthrough Therapy designation from the
Conference Call
Savara management will host a conference call and live audiovisual webcast to discuss the IMPALA-2 results at
About the IMPALA-2 Trial
IMPALA-2 is a global, pivotal, Phase 3, 48-week, randomized, double-blind, placebo-controlled clinical trial designed to compare the efficacy and safety of molgramostim 300 mcg administered once daily by inhalation with matching placebo in patients with aPAP. The trial is being conducted at 43 clinical trial sites across 16 countries in the
About aPAP
Autoimmune PAP is a rare lung disease characterized by the abnormal build-up of surfactant in the alveoli (or air sacs) of the lungs. Surfactant consists of proteins and lipids and is an important physiological substance that lines the alveoli to prevent them from collapsing. In a healthy lung, excess surfactant is cleared and digested by immune cells called alveolar macrophages. Alveolar macrophages need to be stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) to function properly in clearing surfactant, but in autoimmune PAP, GM-CSF is neutralized by antibodies against GM-CSF, rendering the macrophages unable to adequately clear surfactant. As a result, an excess of surfactant accumulates in the alveoli, causing impaired gas exchange, resulting in clinical symptoms of shortness of breath, often with cough and frequent fatigue. Patients may also experience episodes of fever, chest pain, or coughing up blood, especially if secondary lung infection develops. In the long-term, the disease can lead to serious complications, including lung fibrosis and the need for a lung transplant.
About Savara
Savara is a clinical stage biopharmaceutical company focused on rare respiratory diseases. Our lead program, molgramostim nebulizer solution, is an inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) in Phase 3 development for autoimmune pulmonary alveolar proteinosis (aPAP). Molgramostim is delivered via an investigational eFlow® Nebulizer System (
Forward-Looking Statements
Savara cautions you that statements in this press release that are not a description of historical fact are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words referencing future events or circumstances such as “expect,” “intend,” “plan,” “anticipate,” “believe,” and “will,” among others. Such statements include, but are not limited to, statements related to the anticipated timing of the submission of a Biologics License Application; that there is a high unmet need in aPAP for a pharmacotherapy; that the evidence now clearly demonstrates molgramostim has the potential to be a safe and efficacious treatment option for aPAP patients; statements regarding the therapeutic benefits of molgramostim in aPAP and the impact of molgramostim on quality of life for aPAP patients; that the strong efficacy data and favorable benefit-risk profile potentially position molgramostim to be the first and only approved therapeutic for aPAP in the
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