The FDA rejected Ampio Pharmaceuticals’ (NYSE American:AMPE) proposed modified intent-to-treat (mITT) population as the primary analysis population for evaluating efficacy in the AP-013 trial, and the acceptability of AP-013 as a second pivotal trial to support a biologics license application (BLA) for Ampion, which is in development for the treatment of severe osteoarthritis of the knee.
The FDA did not agree with the company’s proposed change from the intent-to-treat population to the mITT population for the primary endpoint analysis, and that mITT is a substantive and material change to the Protocol and Statistical Analysis Plan that is not in accordance with the Special Protocol Assessment agreement.
Despite the COVID-related impact on patients and trial centers during the trial, the company should have sought FDA’s agreement on these changes prior to analyzing and unblinding the data.
In addition, the FDA did not agree that AP-013 could serve as a second pivotal trial for Ampion based on both the change in the analysis population and the analysis of pain only instead of the original prespecified co-primary endpoints.
“We are very disappointed in FDA’s answer,” Mike Martino, chairman and CEO of Ampio, said in a statement.
Despite the unmet medical need of severe osteoarthritis of the knee, Mr. Martino said it will be very difficult to salvage AP-013 itself as a pivotal trial. “Nonetheless, we and our regulatory experts believe there may be ways to do that, and we will follow-up with the FDA in the near term to discuss those options,” he added.
“However, I want to be clear,” Mr. Martino said. “At this point, I believe the best path forward for Ampio and Ampion is likely conducting a new Phase 3 trial. This management team has learned a great deal from conducting and analyzing the prior trials, including AP-013, and believe we are positioned to design and execute a trial that can lead to BLA approval.”