Savara Shares Plummet After Late-Stage Study Failure

Shares of Texas-based Savara are down more than 72% in premarket trading after the company announced its late-stage autoimmune alveolar pulmonary proteinosis (aPAP) treatment failed to hit its primary endpoint.

Savara said the Phase III IMPALA evaluation of Molgradex, an inhaled formulation of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), did not hit the main endpoint of improved lung function in the rare lung disease. The company said an average alveolar-arterial oxygen gradient A-aDO₂ improvement was 12.1 mmHg in the continuous dosing arm. In the placebo arm, the average A-aDO₂ improvement was 8.8 mmHg, which was not statistically significant.

Pulmonary alveolar proteinosis is caused by a build-up of proteins and other substances in the alveoli. aPAP is the most common type of the disease and is believed to represent about 90% of adults who get it, according to the Cleveland Clinic.

While the primary endpoint was not met, Savara is pointing to the secondary endpoints as a possible means forward for the drug. The company said there was an average improvement of 12.3 points in a quality of life measure for patients treated with Molgradex compared to 4.7 points in the placebo arm. The estimated treatment difference was 7.6 points which was statistically significant and approximately two times the generally accepted clinically meaningful difference of four points for this measure, the company said.

In addition to the A-aDO₂, the secondary endpoint of diffusing capacity of the lungs for carbon monoxide was assessed to evaluate the efficacy of Molgradex on gas transfer. Patients in the continuous dosing arm showed a mean improvement of 11.6%, while the placebo arms showed a 7.7% predicted and 3.9% predicted improvement, respectively. The estimated treatment difference of 7.9% between the continuous dosing arm and placebo was statistically significant.

Savara reported two other secondary endpoints as positive signs, the six-minute walk distance and requirement for whole lung lavage did not show statistically significant improvement despite positive growth.

Savara Chief Executive Officer Rob Neville put a positive spin on the IMPALA outcome and said they “remain encouraged” due to the secondary endpoint targets. Neville said the company plans to meet with both the U.S. Food and Drug Administration and the European Medicines Agency to determine whether or not there is a path forward regarding regulatory approval based on the current data and, perhaps, an additional trial. The company intends to submit the full data set from IMPALA to a peer-reviewed scientific journal or to an upcoming medical meeting for consideration.

Bruce Trapnell, a professor of medicine at University of Cincinnati College of Medicine and lead investigator of the IMPALA study, said the trends in reduction of A-aDO₂, as well as the improvement in the diffusion capacity, are very consistent with reduction of the surfactant burden that causes the clinical symptoms of aPAP.

“Most importantly, the impressive improvement in quality of life, as measured by the SGRQ, suggest that Molgradex not only improved objective measures of oxygenation, but also had a clinically meaningful therapeutic effect. I believe these data demonstrate that Molgradex can become an important pharmacological treatment option for patients with aPAP,” Trapnell said in a statement.

Despite the success of the secondary endpoints, company investors were not impressed and dumped the stock overnight, sending the stock plummeting to $2.95 per share, down from Wednesday’s close of $10.57.