AstraZeneca announced on Wednesday that Enhertu was granted Breakthrough Therapy Designation in the US for patients with HER2-low metastatic breast cancer.
AstraZeneca and Daiichi Sankyo collaborated to create Enhertu, which has received Breakthrough Therapy Designation in the United States for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer who have received prior systemic therapy in the metastatic setting or who have developed disease recurrence during or within six months of completing adjuvant chemotherapy.
Patients with hormone receptor-positive breast cancer should have received endocrine therapy or be ineligible for it.
AstraZeneca and Daiichi Sankyo are working together to develop and commercialise Enhertu, a precisely tailored HER2-directed antibody-drug conjugate.
The FDA Breakthrough Therapy Designation expedites the development and regulatory review of possible new medications that are intended to treat a serious ailment and fill a major unmet medical need.
The new treatment, Enhertu must have shown promising preliminary clinical outcomes that show a significant improvement over existing medicines on a clinically important endpoint.
Up to half of all breast cancer patients have tumours with a HER2 immunohistochemistry score of 1+ or 2+ in combination with a negative in-situ hybridisation test, a level of HER2 expression that makes them ineligible for HER2-targeted therapy at this time. For individuals with metastatic breast cancer, HER2 testing is commonly used to determine the best treatment options.
Targeting the lower end of the HER2 expression spectrum could be another way to slow disease progression and extend survival in metastatic breast cancer patients. Chemotherapy is now the only treatment option for HR-positive tumours that have progressed on endocrine (hormone) therapy. Those who are HR-negative have a limited number of possibilities.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said, “Today’s news is a significant validation of the potential we see for the historic DESTINY-Breast04 trial to enable a paradigm shift in how breast cancer is classified by targeting the full spectrum of HER2 expression.”
“Enhertu continues to show transformative potential, and this milestone represents an important advance for patients with HER2-low metastatic breast cancer who are in urgent need of new treatment options and better outcomes.”
Based on findings from the key DESTINY-Breast04 Phase III study, which showed good high-level results in February 2022, the FDA awarded the Breakthrough Therapy Designation.
Enhertu showed a statistically significant and clinically meaningful improvement in progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic breast cancer in all randomly selected patients with HR-positive and HR-negative disease compared to the physician’s choice of chemotherapy, which is the current standard of care, in the trial.
Enhertu’s safety profile was similar to that of prior clinical trials, with no new safety issues discovered. The findings will be presented at a medical conference in the near future.
Enhertu has now been designated as a Breakthrough Therapy in breast cancer for the third time.
Enhertu previously obtained Breakthrough Therapy Designations in 2021 and 2017 for the treatment of second-line HER2-positive metastatic breast cancer and later-line HER2-positive metastatic breast cancer, respectively.
In 2020, Enhertu received two more Breakthrough Therapy Designations for HER2-mutant metastatic non-small cell lung cancer and HER2-positive metastatic gastric cancer.
“Historically, only patients with HER2-positive metastatic breast cancer were shown to benefit from HER2-directed therapy,” added Ken Takeshita, Global Head, R&D, Daiichi Sankyo.
“DESTINY-Breast04, in which Enhertu showed a clinically meaningful survival benefit in patients with HER2-low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients.”
“This Breakthrough Therapy Designation acknowledges the potential of Enhertu to fulfil an unmet medical need and we look forward to working closely with the FDA to bring the first HER2-directed therapy to patients with metastatic breast cancer whose tumours have lower levels of HER2 expression.”
AstraZeneca shares have dropped 0.25% to 18.8p despite Enhertu receiving another Breakthrough Therapy Designation.