FDA Requests Additional Manufacturing Data for Savara's Molgramostim, Delaying Potential Approval

In a setback for Savara's respiratory asset molgramostim, the U.S. Food and Drug Administration (FDA) has issued a refuse to file (RTF) letter for the biotech's biologics license application (BLA). The decision, announced on May 27, 2025, stems from a need for additional chemistry, manufacturing, and controls (CMC) data, potentially pushing back the drug's approval timeline for the treatment of autoimmune pulmonary alveolar proteinosis (aPAP).

FDA's Refusal and Requested Information

The FDA determined that Savara's initial filing was "not sufficiently complete to permit substantive review," according to the company's press release. The regulatory body has requested additional CMC data, suggesting manufacturing-related issues may have influenced the decision. Importantly, the FDA did not raise any safety concerns about molgramostim or request additional efficacy studies.

Savara CEO Matt Pauls expressed confidence in addressing the FDA's concerns, stating, "Based on our understanding of the letter, we are confident we can thoroughly address the agency's request and expect to resubmit our [biologics license application] in the fourth quarter of 2025." The company is already in the process of generating the requested CMC data.

Molgramostim and aPAP: A Potential Breakthrough

Molgramostim, intended to be marketed under the trade name Molbreevi, is being developed to treat aPAP, a rare disease that clogs the air sacs in the lungs. This condition can lead to serious complications, including lung fibrosis and the potential need for lung transplantation.

As a granulocyte-macrophage colony-stimulating factor, molgramostim is designed to clear surfactant—a mixture of fat and proteins—from the alveoli in the lungs. The drug is administered via an investigational nebulizer specifically designed by Germany's PARI Pharma for use with molgramostim.

Savara's Commercial Preparations and Setbacks

Despite the current regulatory hurdle, Savara had been making commercial preparations for molgramostim's potential launch. In September 2024, the company hired Braden Parker, formerly of Orchard Therapeutics, as its chief commercial officer to assist with the drug's launch, which was initially projected for late 2025 or 2026.

The company also sponsored an episode of "The Balancing Act," a morning talk show on Lifetime, in October 2024. The program highlighted patient stories with rare and genetic diseases, focusing primarily on aPAP, molgramostim's intended indication.

Savara's commitment to molgramostim follows a significant pipeline restructuring in 2020, during which the company discontinued multiple other assets to focus on aPAP treatment. This latest setback underscores the challenges faced by biotechnology companies in bringing novel treatments for rare diseases to market, even in the later stages of development.