Pharmaceutical Business review

Daiichi Sankyo, AstraZeneca’s ENHERTU gets BTD for HER2 Low Metastatic Breast Cancer

ENHERTU received BTD to treat adult patients with unresectable or metastatic HER2 low breast cancer. Credit: Sharon McCutcheon from Pixabay

This treatment is meant for patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer patients who have earlier received a systemic therapy in the metastatic setting or have developed disease recurrence during or within six months of completing adjuvant chemotherapy.

The adult patients with hormone receptor (HR) positive breast cancer should additionally either have received or be not eligible for endocrine therapy.

ENHERTU is a particularly engineered HER2 directed antibody drug conjugate (ADC) being developed and commercialised together by the two companies.

The BTD was given based on data from the crucial DESTINY-Breast04 phase 3 trial where ENHERTU showed a statistically important and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients diagnosed with HER2 low unresectable and/or metastatic breast cancer with HR positive or HR negative disease as against a physician’s choice of chemotherapy, which is the present standard of care.

Recently, the positive topline results of DESTINY-Breast04 were announced. This data will be revealed at an upcoming medical meeting.

The safety profile of ENHERTU was found to be in line with earlier clinical trials with no new safety concerns.

The interstitial lung disease (ILD) rates were in line with those seen in late-line HER2 positive breast cancer trials of ENHERTU with a lower rate of grade 5 ILD seen, as determined by an independent adjudication panel.

Daiichi Sankyo global head of research and development Ken Takeshita said: “Historically, only patients with HER2 positive metastatic breast cancer were shown to benefit from HER2 directed therapy. 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 fulfill 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 tumors have lower levels of HER2 expression.”

AstraZeneca executive vice president for oncology R&D Susan Galbraith 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.”

This is the third BTD for ENHERTU with regard to breast cancer.

Earlier, ENHERTU secured BTDs to treat second-line HER2 positive metastatic breast cancer last year, and later-line HER2 positive metastatic breast cancer in 2017.

Further two BTDs for ENHERTU have been granted in 2020 for HER2 positive metastatic gastric cancer, and HER2 mutant metastatic non-small cell lung cancer (NSCLC).