The new drug application was based on data from a single, pivotal, randomized, controlled, phase 3 study of encequidar for the treatment of metastatic breast cancer.
The FDA has accepted and granted priority review to the filing of a new drug application (NDA) for oral paclitaxel and encequidar (oral paclitaxel) for the treatment of metastatic breast cancer, according to Athenex, the developer of the agent.1
A prescription drug user fee act (PDUFA) date has been set by the FDA for February 28, 2021. In addition, the FDA indicated that it is not currently intending to hold an advisory committee to discuss the application.
“We are delighted to have achieved this major milestone for Athenex. We continue to finalize our commercial preparations to ensure a successful launch of [encequidar], if approved,” Johnson Lau, MBBS, MD, FRCP, chairman and chief executive officer of Athenex, said in a press release. “We see [encequidar] as a potentially important alternative to [intravenous; IV] infusions, especially during the current pandemic, as it may allow cancer patients to take the oral chemotherapy at home. We believe the [encequidar] program validates our broader Orascovery platform, and we are committed to applying the technology to convert other IV chemotherapies into oral agents.”
The NDA submission was based on data from a single, pivotal, randomized, controlled, phase 3 study of encequidar for the treatment of metastatic breast cancer, in which the study achieved its primary end point of a statistically significant improvement in overall response rate (ORR). The study compared the safety and efficacy of encequidar as monotherapy versus IV paclitaxel as monotherapy.
Overall, 402 patients with metastatic breast cancer were enrolled in a 2:1 ratio to receive either encequidar (n = 265) or IV paclitaxel (n = 137) in the intention to treat (ITT) population.2
In the encequidar cohort the ORR was 36% compared to 24% for patients randomized to IV paclitaxel (P = .01). Encequidar also demonstrated statistically significant improvements compared to IV paclitaxel based on other analyses on populations excluding non-evaluable patients, with P-values of 0.01 or less in all analyses. Additionally, the results showed that the proportion of confirmed responders with a duration of response of more than 150 days was 2.5 times higher in the encequidar group than in the IV paclitaxel group.
With a data cut-off of July 25, 2019, there was a strong trend observed in progression-free survival (PFS; P = .077) favoring encequidar over IV paclitaxel, as well as a strong trend in overall survival (OS; P = .11) favoring encequidar over IV paclitaxel. As of the cut-off date, a higher proportion of patients on encequidar compared with IV paclitaxel remained progression-free and Athenex suggested it expects the PFS and OS trend will continue to improve upon follow-up.
Of note, the encequidar cohort also had a lower incidence and severity of neuropathy compared to IV paclitaxel, with 57% of those in the IV paclitaxel group experiencing neuropathy (all grades) compared to 17% of those in the encequidar group. Moreover, grade 3 neuropathy was observed in 8% of those randomized to IV paclitaxel versus 1% of those randomized to encequidar.
The results also revealed a lower incidence of alopecia, arthralgia, and myalgia in the encequidar group. The incidence of neutropenia was similar in both groups, however there were more incidents of grade 4 neutropenia and infection in the encequidar group. Further, there were also more gastro-intestinal side effects in the encequidar group.
“We are working diligently with the FDA on this priority review to bring [encequidar] to patients with metastatic breast cancer as quickly as possible,” Rudolf Kwan, MBBS, MRCP, chief medical officer of Athenex, said in the release. “Intravenous paclitaxel is a foundational chemotherapy in multiple tumor types and we plan to invest in broadening the label and uses for [encequidar].”
Encequidar is also being evaluated in combination with ramucirumab (Cyramza) in patients with gastric cancer in an expansion phase of a phase 1b study, which has shown encouraging preliminary data. The agent also showed encouraging clinical activity in a pilot study of patients with angiosarcoma. Athenex is also testing the combination of encequidar with pembrolizumab (Keytruda) in patients with advanced solid malignancies.
1. Athenex Announces FDA Acceptance for Filing of U.S. NDA for Oral Paclitaxel and Encequidar in Metastatic Breast Cancer with Priority Review [news release]. Buffalo, NY. Published September 1, 2020. Accessed September 1, 2020. http://www.globenewswire.com/news-release/2020/09/01/2086762/0/en/Athenex-Announces-FDA-Acceptance-for-Filing-of-U-S-NDA-for-Oral-Paclitaxel-and-Encequidar-in-Metastatic-Breast-Cancer-with-Priority-Review.html
2. Athenex Announces Oral Paclitaxel and Encequidar had a Significantly Higher Response Rate Over IV Paclitaxel in a Phase III Pivotal Study in Metastatic Breast Cancer [news release]. Buffalo, NY. Published August 7, 2019. Accessed September 1, 2020. https://ir.athenex.com/news-releases/news-release-details/athenex-announces-oral-paclitaxel-and-encequidar-had