This decision comes with the announcement of Savara‘s plan to reduce overall operating expenses, including in workforce, and of a strategy to simplify its pipeline, the company announced in a press release.
Accordingly, Savara said it will focus on the clinical development of Molgradex (molgramostim), an inhaled formulation of the granulocyte-macrophage colony-stimulating factor, for patients with autoimmune alveolar pulmonary proteinosis, or aPAP, a rare lung disorder.
The company expects to launch the IMPALA 2 Phase 3 trial (NCT04544293) in the second quarter of 2021, testing Molgradex for aPAP across North America, Europe, and Asia.
Savara had acquired the global rights to develop and market Apulmiq for the treatment of NCFB from Grifols. Apulmiq was originally developed by Aradigm, which withdrew an application to the European Medicines Agency requesting regulatory approval of the treatment (as Linhaliq) for NCFB patients with chronic lung infections associated with Pseudomonas aeruginosa bacteria.
Ciprofloxacin, the active ingredient in Apulmiq, is an antibiotic commonly used for the treatment of acute lung infections. Specifically, the treatment is made of both free ciprofloxacin, making it promptly available to fight infections, and ciprofloxacin loaded into tiny vesicles, called liposomes. These allow a slow release of the antibiotic into the lungs, enabling less dosing.
Data from two Phase 3 trials — ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245) — showed that Apulmiq was safe. In addition, the treatment extended the time to the first pulmonary exacerbation and lessened the frequency of exacerbations, when compared with a placebo.
However, a statistically significant difference favoring Apulmiq was only seen in ORBIT-4. This was the reason why the U.S. Food and Drug Administration refused to approve the therapy in January 2018, and maintained its decision in 2019.
The FDA recommended a new Phase 3 trial to examine the frequency of pulmonary exacerbations as a main goal, instead of using time to first exacerbation as in the ORBIT trials.
Savara had agreed to work with the FDA in the design of this confirmatory Phase 3 trial for Apulmiq’s approval, before it now announced the shut-down of the therapy’s clinical program.
Additionally, the company has announced that its AVAIL Phase 3 trial (NCT03181932), testing AeroVanc (vancomycin) in cystic fibrosis patients with methicillin-resistant Staphylococcus aureus lung infections, failed to reach its primary goal of improving lung function. Also, no reduction in the frequency of pulmonary exacerbations was seen, compared with a placebo. As a result, the clinical development of AeroVanc also will be discontinued, the company said.