AZ gets FDA nod for Enhertu in first HER2-low cancer

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FDA building

The FDA has approved AstraZeneca and Daiichi Sankyo's Enhertu as the first targeted therapy for HER2-low breast cancer, a new category of the disease that was once lumped under the HER2-negative classification.

It has the potential to be a sizeable new indication for Enhertu (trastuzumab deruxtecan), a HER2-targeting antibody-drug conjugate, and central to AZ and Daiichi Sankyo's hopes of unlocking multibillion-dollar sales for the drug.

According to the FDA, out of the almost 290,000 new cases of breast cancer diagnosed in women in 2022, between 80% to 85% would be considered HER2-negative under the old grouping system.

Around 60% of that HER2-negative group can now be considered as HER2-low – roughly 140,000 cases using a back-of-the-envelope calculation – who can now consider Enhertu treatment as an alternative to endocrine therapy or chemotherapy.

The new approval is based on the DESTINY-Breast04 study in patients with HER2-low unresectable, metastatic breast cancer who received multiple lines of prior treatment, which headlined at this year's ASCO congress.

In the 557-patient study, Enhertu reduced the risk of disease progression or death by 50%, whilst improving overall survival by 36% compared to chemotherapy – translating to an extra half year of life for patients from 16.8 to 23.4 months.

That impressive data helped the FDA arrive at a decision to extend the use of Enhertu into the HER2-low setting four months ahead of schedule and with a broad label.

The US regulator has cleared the ADC for patients if they have received prior chemotherapy in the metastatic setting, or if their cancer returned during, or within six months of completing, adjuvant chemotherapy.

Enhertu can also be prescribed to patients regardless of their hormone receptor (HR) status, so is an option for HR-positive as well as potentially some triple-negative breast cancer (TNBC) patients, with the potential to encroach on Gilead Sciences' ADC Trodelvy (sacituzumab govitecan) in those settings.

Enhertu is also approved as a second- and third-line therapy for HER2+ metastatic breast cancer and a second-line therapy for HER2+ metastatic gastric cancer.

Regulatory applications for Enhertu are also currently under review in Europe, Japan and several other countries based on the DESTINY-Breast04 results, said AZ.