After winning a standing ovation at the recent American Society of Clinical Oncology meeting, Enhertu’s HER2-low breast cancer data are now getting the VIP treatment at the FDA. And the drug’s developers, AstraZeneca and Daiichi Sankyo, are targeting an ambitiously broad patient population.
The FDA has granted a priority review to AZ and Daiichi’s bid to expand Enhertu into previously treated HER2-low breast cancer, the two companies said Monday.
Further, the agency is smoothing the process with two more expedited review programs. It’s reviewing the submission under the Real-Time Oncology Review pathway, which allows for early evaluation of data before completion of an application package. And it's putting the application into Project Orbis, which means foreign regulators can partake in the review.
The priority review sets an FDA decision for the fourth quarter of 2022, although the companies didn’t give the exact target action date.
With Enhertu’s new application, AZ and Daiichi aim to open HER2-low disease as an entirely new treatment category. By the two companies’ definition, tumors are considered HER2-low when they test immunohistochemistry (IHC) 1+, or if they test IHC 2+ but in situ hybridization-negative. Currently, these two scenarios are both grouped as HER2-negative.
SVB Securities analyst Andrew Berens, M.D., has recently projected that Enhertu could hit $4.6 billion sales in HER2-low patients alone by 2030.
AZ and Daiichi are targeting a very broad population of patients with unresectable or metastatic HER2-low breast cancer after just one prior therapy in the metastatic setting. Their application includes data on both HR-positive and HR-negative disease, a Daiichi spokesperson confirmed to Fierce Pharma.
For this application, Enhertu proved its case in the Destiny-Breast04 trial. In patients with previously treated HER2-low breast cancer, the HER2-targeted antibody-drug conjugate pared down the risk of disease progression or death by 50% and the risk of death by 36% compared with physician’s choice of chemotherapy.
The indication represents a bold ask on AZ and Daiichi’s part. First of all, the two companies are shooting for an approval after just one line of prior treatment in the metastatic setting. But patients enrolled in Destiny-Breast04 had received a median three lines of prior therapy, and nearly 90% of patients had at least two prior treatments for metastatic disease.
Second, of the 557 patients randomized in the study, the current analysis only had 58 HR-negative cases, including 40 on Enhertu and 18 on chemo. But AZ and Daiichi are apparently requesting a label regardless of HR status.
Enhertu’s performance did appear consistent in that small group of patients with HR-negative disease, otherwise also known as triple-negative breast cancer. In an exploratory analysis, Enhertu cut the risk of disease progression or death by 54% and the risk of death by 52% in those patients.
The companies included the HR-negative population in Destiny-Breast04 at the recommendation of the FDA, AZ’s oncology R&D chief Susan Galbraith, Ph.D., told Fierce Pharma during ASCO. She also pointed to the “unmet need and the quality of the data that we’ve seen and consistency across different groups.”
During a recent SVB Securities event, two experts told analysts that Enhertu may be used behind aromatase inhibitors and CDK4/6 inhibitors and SERDs initially in HR-positive patients, but that the drug may eventually move to earlier treatment.
One of the experts also argued that it may take some time before Enhertu is used in the HR-negative setting, but both experts expect the drug will eventually show a clear efficacy advantage in this area as data mature.