FDA Grants Priority Review for Oral Paclitaxel and Encequidar in Metastatic Breast Cancer

The FDA has granted a Priority Review to the New Drug Application (NDA) for oral paclitaxel with encequidar for the treatment of patients with metastatic breast cancer after accepting the application for filing, announced Athenex, Inc. in a press release.¹

Per the Prescription Drug User Fee Act, a target action date of February 28, 2021, has been set for a decision on the NDA. The FDA has not made plans for an advisory committee meeting to discuss the NDA for encequidar.

“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. We see oral paclitaxel as a potentially important alternative to IV [intravenous] infusions, especially during the current pandemic, as it may allow [patients with] cancer to take the oral chemotherapy at home,” said Johnson Lau, MBBS, MD, chairman and CEO, Athenex, in a statement. “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.”

The submission of this application is supported by data from a pivotal phase 3 clinical trial of oral paclitaxel in combination with the P-glycoprotein pump inhibitor encequidar for the treatment of metastatic breast cancer, which was a randomized controlled study comparing the safety and efficacy of oral paclitaxel versus IV paclitaxel monotherapy (NCT02594371).

The trial met its primary end point by showing a statistically significant improvement in the overall response rate (ORR) with the oral chemotherapy compared with IV paclitaxel. Lower neuropathy was also observed with the oral agent in this study. The ORR was 36% with the oral therapy versus 24% with IV paclitaxel in the intention-to-treat population (P = .01). In the patients who had confirmed responses, the rate of a duration of response of more than 150 days was 2.5 times higher with the oral therapy versus with IV paclitaxel.²

According to findings with a data cut-off date of July 25, 2019, the study demonstrated a trend toward improved progression-free survival (PFS; P = .077) and overall survival (OS; P = .11) with oral paclitaxel. A higher proportion of patients receiving the oral therapy remained progression free compared with the IV agent.

According to data presented at the 2019 San Antonio Breast Cancer Symposium, the median PFS with oral paclitaxel and encequidar was 9.3 months versus 8.3 months with IV paclitaxel, and the median OS was 27.9 months versus 16.9 months, respectively.³

The company expects that the trends in PFS and OS will continue to improve with follow-up.

A lower incidence of neuropathy, as well as lower severity, was observed with the oral agent compared with IV paclitaxel, whereby 57% of the IV arm experienced neuropathy versus 17% and grade 3 neuropathy was only observed in 8% versus 1% of patients, respectively. A lower incidence of alopecia, arthralgia, and myalgia was also observed in the oral paclitaxel group. The incidence of neutropenia appeared similar between the 2 arms, but more grade 4 neutropenia and infection were observed in the oral arm, as well as more gastrointestinal adverse events.

In the intention-to-treat population, 402 patients with metastatic breast cancer were randomized 2:1 to the oral (n = 265) or IV paclitaxel (n = 137). The patient demographics were well balanced between the 2 arms. The primary end point was ORR confirmed at 2 consecutive time points by RECIST v1.1 criteria.

“We are working diligently with the FDA on this Priority Review to bring oral paclitaxel to patients with metastatic breast cancer as quickly as possible,” stated Rudolf Kwan, MD, chief medical officer of Athenex.¹ “Intravenous paclitaxel is a foundational chemotherapy in multiple tumor types and we plan to invest in broadening the label and uses for oral paclitaxel.”

_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. September 1, 2020. Accessed September 1, 2020. https://yhoo.it/3lxx9SN}

_{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. New Release. August 7, 2019. Accessed September 1, 2020. https://bit.ly/2YPWltS}

_{3. Umanzor G, Rugo HS, Barrios FJ, et al. Oral paclitaxel with encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: A phase III clinical study in metastatic breast cancer. Presented at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS6-01.}