- Savara's inhaled biological drug Molgradex failed in a Phase 3 trial to improve measures of lung function for patients with a rare disease called autoimmune alveolar pulmonary proteinosis (aPAP). Company shares crashed 75% in early trading June 13, dropping its market capitalization to below its March 31 cash balance.
- Executives said they plan to discuss the potential for a regulatory submission with Food and Drug Administration officials based on improvements in patient quality of life detected in the trial.
- Molgradex is available to patients in Europe through a compassionate use program, although the results should raise doubts over its continued use in the condition.
Savara employed a tested and sometimes successful biotech strategy: acquiring a drug already used on a limited basis and running a full clinical trial to justify full regulatory approval, wider use and a higher price. One success story using this strategy is Catalyst Pharmaceutical, which achieved FDA approval for Firdapse (amifampridine), although that drug is now embroiled in a lawsuit.
In Savara's case, it bought Molgradex (molgramostim) through an acquisition of the Danish company Serendex in 2016. The agent is an inhaled granulocyte macrophage colony stimulating factor (GM-CSF), a class of drugs that promotes production of disease-fighting immune cells. In aPAP, antibodies to GM-CSF cause a buildup of fats in the lung sacs called alveoli, interfering with oxygen absorption.
In Europe, Molgradex is made available on a "named-patient" basis, which allows physicians to request a drug directly from a manufacturer.
The Phase 3 IMPALA trial sought to validate that compassionate use by showing Molgradex could improve alveolar-arterial oxygen gradient. Patients inhaling Molgradex saw a 12.1 mgHg increase, but that was not statistically significant compared to the 8.8mgHg increase seen in patients taking a placebo.
Still, Savara executives expressed hope that the FDA would take a friendly view of Molgradex based on improvements in the patient-reported St.George Respiratory Questionnaire, a quality-of-life test. On that measure, patients taking Molgradex improved by 12.3 points on the 18-item questionnaire, compared with 4.7 points for placebo patients.
"We are preparing to meet with the FDA and [European Medicines Agency] to discuss the results from this study and to determine our options to seek approval based on the current data, and potentially conduct an additional study incorporating the learnings from IMPALA," Savara chief executive Rob Neville said in a release.
Savara became a publicly traded company in 2017 following the acquisition of troubled Mast Therapeutics, which had its own clinical failure, and assuming Mast's Nasdaq listing. Since that transaction, Savara has made three secondary share offerings, raising nearly $140 million.