Savara gets FDA breakthrough status despite large, late-stage failure
Savara watched their stock crater in June as they announced a late-stage failure on their lead compound. But now, based on the same Phase III trial, the FDA is giving the biotech and its rare lung disease drug breakthrough therapy designation.
The designation comes for Molgradex, an inhalant meant to treat autoimmune pulmonary alveolar proteinosis (aPAP). It was the lead compound in Savara’s 2016 buyout of Serendex. The disease is caused by autoantibodies that neutralize a protein called GM-CSF in the lungs, and the inhalant replenishes the lungs with a recombinant form of the protein.
Savara said in June that the drug had failed to significantly improve oxygen levels in trial patients’ alveolar, the parts of the lung obstructed in PAP patients. Savara tried to salvage the study, pointing to secondary and “exploratory” endpoints and blaming the primary failure on an unexpectedly high placebo effect. Investors didn’t buy it, tanking their stock price $SVRA 75%.
The FDA, though, appears to think there’s a story there. It’s impossible to know the agency’s thinking, but detailed slides Savara released this fall emphasized “a pattern of improvement” on several metrics in the 139-person trial and argued that the “totality of outcome data” support Molgradex over placebo.
That data included statistically significant improvements on the Saint Georges Respiratory Questionnaire and CT scans. The biotech also argued the primary endpoint (technically called A-aDO2), as well as a walking test called 6MWT, hemoglobin levels and the time before rescue surgery “trended” toward significance.
Molgradex was “effective as shown by changes in lung pathology, physiology, health status, function,” lead investigator Bruce Trapnell wrote.
That still leaves a lot of questions about the benefit for patients, and though investors came back with the breakthrough designation, they didn’t return Savara to its pre-June status. The stock nearly tripled on Monday, from $1.73 per share to $4.91. But that’s still less than half of the $10.57 price on June 12.
The news may also bolster confidence in Savara’s other programs. Those include a Phase II trial applying Molgradex to nontuberculous mycobacteria, with results expected early this year, and a now-enrolling study applying the drug to nontuberculous mycobacteria in cystic fibrosis patients. There’s also a vancomycin inhalant for MRSA infections in CF patients, with Phase III results expected in about a year.