FDA's action marks an abrupt change of course from the Priority Review granted September 2020.
FDA has sent Athenex a complete response letter (CRL) regarding the company’s new drug application (NDA) for oral paclitaxel plus encequidar for the treatment of metastatic breast cancer. The company announced the CRL early Monday and issued a statement along with other developments as part of its financial update for 2020.
Regulators called for a new “adequate and well-conducted clinical trial,” marking an about-face from the course Athenex seemed to be on when the company’s NDA was accepted for Priority Review in September 2020. The targeted action date was February 28, 2021.
FDA cited concerns about the risk to patients of increased neutropenia-related adverse events in the oral paclitaxel arm compared with the intravenous (IV) paclitaxel arm. Regulators also said they were concerned about the uncertainty over results of the primary end point of the objective response rate (ORR) at week 19 conducted by a blinded independent central review (BICR).
In its statement, Athenex said, “The agency stated that the BICR reconciliation and re-read process may have introduced unmeasured bias and influence on the BICR.”
Athenex officials expressed their surprise at the turn of events, and said they would request a meeting with FDA to discuss the response and a plan to move forward.
“Our clinical and regulatory teams are disappointed by the complete response letter,” Rudolf Kwan, MD, chief medical officer of Athenex, said in the statement. “We plan to work with the agency to resolve the issues raised in the CRL and to obtain approval for oral paclitaxel plus encequidar in metastatic breast cancer.”
The application was supported by data from a phase 3 trial that showed oral paclitaxel plus encequidar improved ORR compared with IV paclitaxel in patients with metastatic breast cancer; the ORR for the study drug was 36% compared with 24% for the control arm. Duration of response among those who responded to treatment was long as well, at 150 days or 2.5 times longer in those given oral paclitaxel with encequidar compared with IV paclitaxel.
Rates of neutropenia were comparable between the 2 arms, but more patients who took the study drug had grade 4 neutropenia and were more likely to have gastrointestinal side effects.
During the conference call, Athenex officials said the issue of whether the study population was representative of a US population also came up during the review process. The study arm of patients taking the combination drug was 90% Hispanic, 1% Black, and 7% White. According to the US Census Bureau, the nation’s population is 18.5% Hispanic, 13.4% Black, and 60% White.
Johnson Lau, MBBS, MD, FRCP, CEO of Athenex, said, “We remain committed to the breast cancer community and will explore the best path forward to obtain regulatory approval. In the interim, we will identify and undertake the appropriate internal organizational adjustments accordingly.”