FDA Grants Priority Review to Oral Paclitaxel/Encequidar for Metastatic Breast Cancer

The FDA has granted a priority review to a new drug application (NDA) for oral paclitaxel and encequidar (oral paclitaxel) for use in patients with metastatic breast cancer, according to an announcement from Athenex, Inc.¹

The application was based on findings from a single pivotal phase 3 trial, which compared the use of encequidar and oral paclitaxel with intravenous (IV) paclitaxel monotherapy. Results showed that that the combination of encequidar and oral paclitaxel elicited a statistically significant overall response rate (ORR) compared with IV paclitaxel in this population, meeting the primary end point of the trial.²

Specifically, the ORR achieved with the encequidar regimen was 36% compared with 24% with IV paclitaxel (P = .01). Moreover, the rate of those who responded to treatment and experienced a duration of response of 150 days or longer was 2.5 times greater in the experimental arm versus the control arm.

Under the Prescription Drug User Fee Act, the FDA must make a decision on the NDA by February 28, 2021.

“We are delighted to have achieved this major milestone for Athenex. We continue to finalize our commercial preparations to ensure a successful launch of oral paclitaxel, if approved,” Johnson Y.N. Lau, MBBS, MD, FRCP, chairman and chief executive officer of Athenex, stated in a press release. “We see oral paclitaxel as a potentially important alternative to IV infusions, especially during the current pandemic, as it may allow [patients with] cancer to take the oral chemotherapy at home.”

Encequidar, formerly referred to as HMA30181A, is an investigational P-gp inhibitor that was designed to encourage oral absorption, allowing for agents that are currently only available via injection to be administered through the oral route.

A total of 402 patients with metastatic breast cancer were enrolled to the randomized, controlled phase 3 trial. Participants were randomized 2:1 to receive either encequidar/oral paclitaxel (n = 265) or IV paclitaxel (n = 137). Patient characteristics at baseline were found to be well balanced between the 2 treatment arms. The primary end point of the trial was ORR per via RECIST v1.1 criteria at 2 consecutive time points.

At the July 25, 2019 data cutoff date, results illustrated a trend toward a progression-free survival advantage with the investigational regimen compared with IV paclitaxel (P = .077). A trend toward an overall survival benefit was also reported in the arm that received encequidar (P = .11).

With regard to safety, encequidar was found to result in lower rates of neuropathy compared with IV paclitaxel. Across all grades, the neuropathy rate in the control arm was 57% versus just 17% in the investigational arm; rates of grade 3 neuropathy were 8% versus 1%, respectively. Moreover, patients who received the encequidar regimen also experienced lower rates of alopecia, arthralgia, and myalgia.

Neutropenia rates proved to be comparable between the 2 treatment arms, although more patients who received the encequidar regimen reported more grade 4 neutropenia and infection. Patients on the investigational arm also experienced gastrointestinal adverse effects at higher rate than those who were on the control arm.

“We believe the Oral Paclitaxel program validates our broader Orascovery platform, and we are committed to applying the technology to convert other IV chemotherapies into oral agents,” added Lau in the release.

References

1. Athenex announces FDA acceptance for filing of US NDA for oral paclitaxel and encequidar in metastatic breast cancer with priority review. News release. Athenex, Inc. September 1, 2020. Accessed September 1, 2020. https://bit.ly/2YUOfQE.
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. Athenex, Inc. August 7, 2019. Accessed September 1, 2020. https://bit.ly/2OLV7gN.