The FDA has delayed its approval decision on Beren Therapeutics’ rare disease drug candidate, extending the asset’s long path toward the U.S. market.
In February, the FDA accepted adrabetadex, an investigational cyclodextrin therapy, for priority review in Niemann-Pick disease type C. The action positioned the agency to reach its decision by Aug. 17. That timeline was undone by Beren’s reply to the FDA’s request for updates and clarifications to existing data and supporting documentation, which the agency classed as a major amendment to the filing.
Needing time to review the updates and clarifications, the FDA has pushed the decision date back to Nov. 17. The three-month delay is the latest twist in a saga that dates back to the 2009 discovery that a cyclodextrin delayed clinical disease onset in mice.
The National Institutes of Health built on the finding and partnered the program with Vtesse, a biotech that launched in 2015 with $25 million and plans to power into a phase 2/3 trial. Vtesse began the trial that year and was acquired for $200 million upfront by Sucampo in 2017. Mallinckrodt agreed to acquire Sucampo for $1.2 billion later that year.
Then the previously fast-moving program stalled, with the phase 2/3 trial failing in 2018. Mandos, a subsidiary of Beren, acquired the asset in 2021 as part of Mallinckrodt’s bankruptcy process. Beren worked to find a path to market, leading to a filing for FDA approval late last year.
The filing is based on evidence that adrabetadex improves survival. Beren generated (PDF) the evidence by comparing overall survival (OS) in patients who received the cyclodextrin in the phase 2/3 program to an external control arm. After five years, OS in the adrabetadex population was 84%, versus 42% in the control group.
Companies relying on external control arms have suffered regulatory setbacks in the past year. The FDA raised concerns about a natural history control arm in rejecting Regenxbio’s filing for approval of a gene therapy, and pushed back against uniQure’s plan to seek approval based on external control.
