Clinical-stage biopharmaceutical company Savara Inc. was founded on a desire to develop innovative therapies for people living with rare respiratory diseases. The company’s work over the past few years centers around advancing molgramostim. Molgramostim, inhaled via an investigational eFlow® Nebulizer System, is a recombinant form of human granulocyte macrophage colony stimulating factor designed to treat autoimmune pulmonary alveolar proteinosis (aPAP).
Followng positive data from the Phase 2/3 IMPALA clinical study, molgramostim earned Breakthrough Therapy Designation in 2019. Savara chose to move forward in clinical development with the Phase 3 IMPALA-2 study. In fact, Savara shared recently, the company enrolled 164 participants for IMPALA-2. Their goal was 160 participants.
During the course of the study, participants will receive either 300 mcg molgramostim daily or a placebo. Researchers hope to understand how the therapy improves diffusing capacity for carbon monoxide, exercise tolerance, and other measures of lung function. Preliminary efficacy data should be available by week 24 of the trial, though the study will follow participants through week 48. At this point, the trial investigators will also assess safety measures. As such, Savara hopes to report top-line results by Q3.
Understanding Autoimmune Pulmonary Alveolar Proteinosis (aPAP)
Autoimmune pulmonary alveolar proteinosis is the most common form of pulmonary alveolar proteinosis – but is still considered to be a rare autoimmune lung disease. An estimated 300 to 3,000 people across the U.S. have aPAP. Most often, aPAP manifests between 20 to 50 years old. This rare condition occurs when IgG antibodies inhibit granulocyte-macrophage colony-stimulating factor. Normally, granulocyte-macrophage colony-stimulating factor helps clear old lung surfactant. In aPAP, excess lung surfactant builds up, preventing alveolar gas exchange.
Some individuals with aPAP may remain asymptomatic (showing no symptoms). Others may experience:
- A chronic cough
- Unintentional weight loss
- Pain in the chest
- Progressively worsening difficulty breathing
- Exercise intolerance
- Shortness of breath that worsens with exertion
- Episodic fevers
- General malaise
- Cyanosis, a bluish skin discoloration (in rare cases)
- Swollen fingertips (in rare cases)
aPAP may cause potentially severe or serious complications, such as secondary lung infections and coughing up blood, lung scarring, and significantly decreased lung function.
Right now, there are few effective therapies for aPAP. As Savara explains:
Today, there are no approved pharmaceutical treatments available for aPAP. The current standard-of-care is a Whole Lung Lavage (WLL), which does not treat the underlying cause of the disease [and] is an invasive and inconvenient procedure that must be performed by highly experienced physicians at specialist sites and necessitates hospitalization and admission to intensive care afterwards.
For this reason, identifying novel treatment options is increasingly urgent and important.
