AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The approval by the Food and Drug Administration (FDA) was based on positive results from the DESTINY-Breast03 Phase III trial that showed Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p
The approval was granted under the FDA's Real-Time Oncology Review (RTOR) programme and converts the accelerated approval of Enhertu in later line HER2-positive metastatic breast cancer to standard approval, broadening Enhertu's breast cancer indication in the US to earlier lines of use in patients with HER2-positive metastatic breast cancer.
Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program for Sarah Cannon Research Institute, Nashville, Tennessee, US, said: "Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today's approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment."
Catherine Ormerod, Executive Vice President, Strategy and Mission, Living Beyond Breast Cancer, said: "This is an important day for the breast cancer community. With this approval, Enhertu now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease."
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Enhertu is already established in the later-line treatment of patients with HER2-positive metastatic breast cancer, and we are thrilled that with this approval, patients in the US will now be able to access the transformative potential of Enhertu earlier in their treatment. We look forward to bringing this important, potentially paradigm-shifting medicine to even more patients across the globe in an earlier setting as quickly as possible."
Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: "Today's FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA's accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer. Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to T-DM1 in an earlier setting of HER2-positive metastatic breast cancer."
The DESTINY-Breast03 Phase III trial results were recently published online in The New England Journal of Medicine.1 In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.
Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (Enhertu) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines®) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.2
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel's Ministry of Health Pharmaceutical Administration and Switzerland's Swissmedic.
This approval follows the recent Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this earlier setting.
Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.
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Financial considerations
Following this approval for Enhertu in the US, an amount of $100m is due from AstraZeneca to Daiichi Sankyo as a 2nd-line milestone payment in HER2-positive metastatic breast cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.
