AstraZeneca and Daiichi Sankyo sprint to market after FDA clears Enhertu in just two weeks
Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.
The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.
Enhertu is now the first therapy approved to treat patients with HER2-low breast cancer, a newly defined subset of HER-2 negative breast cancer patients, according to the FDA. About 60% of HER2-negative patients fall into the HER2-low bucket, meaning they have some HER2 proteins, but not enough to be classified as HER2-positive, regulators said in a news release.
Patients can take the drug if they’ve received a prior chemotherapy in the metastatic setting, or seen their cancer return within six months of completing adjuvant chemotherapy.
“This approval in HER2-low breast cancer is probably one of the most meaningful approvals in the breast cancer space in decades, both in terms of redefining the way breast cancer patients are classified, as well as offering a treatment option in an area of such significant unmet need,” Ashley Gaines, AstraZeneca’s VP and US franchise head of the breast cancer business, told Endpoints News.
Gaines added that the company has an “extensive educational plan” in place to start educating healthcare providers and patients on Enhertu and how to classify HER2-low patients.
The approval was based on data from the DESTINY-Breast04 study, which AstraZeneca and Daiichi unveiled earlier this year at ASCO to a standing ovation.
Of the 494 hormone receptor positive (HR+) patients, those on Enhertu saw a 49% reduction in the risk of disease progression or death compared to chemotherapy (P<0.0001). Across all patients (including 63 hormone receptor negative (HR-) patients), researchers saw “a similar 50% reduction in the risk of disease progression or death,” compared to chemotherapy, according to a news release.
Median progression-free survival was 9.9 months in the Enhertu population, compared to 5.1 months in the chemo arm.
The drug did, however, get slapped with boxed warnings for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Treatment-related ILD or pneumonitis occurred in 12% of patients, the majority of which were low-grade, according to the partners. Three patients in the trial died from ILD or pneumonitis, as well as two patients from sepsis, and others from ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion and respiratory failure.
“Early detection and intervention is key in ensuring that patients can be well-managed, and that has been and continues to be a critical education priority for us,” particularly with ILD, Gaines said.
Enhertu was first approved back in December 2019 in HER2-positive breast cancer, and has since racked up indications in earlier breast cancer settings and some types of gastric cancer. AstraZeneca paid $1.35 billion upfront for the collaboration rights back in 2019, and upon the new approval, the pharma giant owes Daiichi Sankyo another $200 million in milestone payments.
It comes at a good time, as Daiichi lost a bid just a couple weeks ago to escape a $42 million patent infringement case. A jury awarded Seagen back in April after finding that Daiichi infringed on a patent for its antibody-drug conjugate technology in the development of Enhertu — and despite an effort by Daiichi to appeal the decision, a Texas federal judge upheld it last month.
Daiichi said at the time that it would continue to explore its options to contest the ruling.
Upon announcing Enhertu’s new indication, the FDA noted the Cancer Moonshot initiative, an Obama-era mission reignited by President Joe Biden back in February with the goal of reducing the cancer death rate by at least 50% over the next 25 years. Just weeks ago, the president tapped a Cancer Cabinet to get things moving.
“Enhertu’s approval further illustrates how the FDA’s efforts align with the Cancer Moonshot goals of targeting the right treatments to the right patients, speeding progress against the most deadly and rare cancers, and learning from the experience of all patients,” the FDA said in a news release.
This article has been updated to clarify that Enhertu’s approval came less than two weeks after the sBLA acceptance.