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The FDA supported Athenex to continue developing oral paclitaxel and encequidar for patients with metastatic breast cancer.
Athenex provided detailed analyses and further overall survival (OS) data on patient subgroups to the FDA at a recent Type A meeting to discuss the deficiencies noted in a complete response letter (CRL) regarding the use of oral paclitaxel and encequidar to treat patients with metastatic breast cancer, according to a press release from the global biopharmaceutical company.1
The additional data and analyses on patient subgroups helped Athenex to spotlight a more detailed look at the risks and benefits of the combination. The drug company also suggested collecting more OS data in order to better inform the design of a new clinical trial. This led to the FDA encouraging Athenex to continue developing the combination for treatment.
“We appreciate the FDA’s support for the development of oral paclitaxel and encequidar in this meeting and expect to maintain a collaborative dialogue on this program,” Rudolf Kwan, MBBS, MRCP, chief medical officer of Athenex, said in a press release. “We continue to believe that, if approved, oral paclitaxel and encequidar has the potential to address a major unmet need in metastatic breast cancer. We hope to agree on a program that is capital efficient and will result in value creation for our stakeholders.”
The original CRL was introduced by the FDA in March 2021, suggesting that the new drug application for oral paclitaxel and encequidar was not ready for approval as currently constructed. The FDA cited concerns with regard to the combination’s safety profile—specifically the high rates of neutropenia-related sequalae with the oral drug vs intravenous administration—and the results of the primary end point of overall response rate at week 19, investigated by blinded independent central review.2
“Our clinical and regulatory teams are disappointed by the complete response letter,” Kwan said in a press release in response to the FDA’s decision in February. “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 FDA recommended that Athenex implement a “well-designed and well-conducted” clinical trial to address these deficiencies, with the CRL specifically suggesting risk mitigation strategies to improve toxicities such as dose optimization or exclusion criteria for patients. Athenex expects to announce plans for an updated clinical trial to be presented to the FDA towards the end of 2021.
The initial application was supported by data from the randomized, multinational phase 3 KX-ORAX-001study (NCT02594371), investigating oral paclitaxel plus encequidar versus intravenous paclitaxel in a cohort of women with metastatic disease. According to the study's updated phase 3 findings, which were presented at the 2020 San Antonio Breast Cancer Symposium, women within the modified intent-to-treat (mITT) population achieved a median OS of 23.3 months vs the control arm (16.3 months; HR, 0.735; 95% CI, 0.556-0.972; P = .0262).3 The mITT cohort also experienced a median progression-free survival of 8.4 months, translating to a 26% reduction in risk of disease progression or death (HR, 0.735; 95% CI, 0.556-0.972; P = .0262).
The global biopharmaceutical company is also developing the combination to treat patients with cutaneous angiocarcinoma, which was granted Orphan Drug Designation by the FDA.