Daiichi Sankyo Submits sNDA in Japan for Enhertu in HER2-Positive Metastatic Breast Cancer, Demonstrating Superiority Over Kadcyla
Dec 25, 2021 00:39
CST Updated
00:39
AstraZeneca
Biopharmaceutical Manufacturer
Daiichi-Sankyo
Pharmaceutical R&D Developer
December 24, 2021 /BioValleyBIOON/ -- Daiichi Sankyo Company Limited recently announced that it has submitted a supplemental New Drug Application (sNDA) to Japan's Ministry of Health, Labour and Welfare (MHLW) for Enhertu (trastuzumab deruxtecan): for the treatment of unresectable or recurrent HER2-positive patients who have previously received trastuzumab and taxane.Breast CancerPatient.Enhertu is a HER2-targeted antibody-drug conjugate (ADC)., by Daiichi Sankyo andAstraZenecaCo-development. In October this year, based on the preliminary data from the DESTINY-Breast03 trial, the U.S. FDA granted Enhertu Breakthrough Therapy Designation (BTD). To date, Enhertu has been approved in the U.S.FDAGranted 4 BTDs, 2 of which are for the treatment of breast cancer.
Breast cancer is the most common type of cancer and one of the leading causes of cancer-related deaths. Approximately 20% of breast cancers are HER2-positive. Despite initial treatment with trastuzumab and taxanes, patients with HER2-positive metastatic breast cancer often experience disease progression and require additional treatment options to further delay progression and prolong survival.
This sNDA is based on the results of the groundbreaking head-to-head pivotal Phase 3 DESTINY-Breast03 trial. Relevant data were presented in September this year at the 2021 European Society for Medical Oncology (ESMO) Congress.TumorAnnounced at the ESMO Virtual Congress. The data shows：In HER2-positive unresectable and/or metastatic breast cancer patients previously treated with trastuzumab and taxanes, Enhertu demonstrated significantly superior efficacy compared to Roche's HER2-targeted ADC product, Kadcyla.（trastuzumab emtansine，T-DM1），Highly Consistent and Significant Benefits Observed Across Multiple Efficacy Endpoints and Key Subgroups。
Kadcyla is a targeted drug approved for the treatment of HER2-positive breast cancer patients mentioned above. DESTINY-Breast03 is the first global Phase 3 head-to-head trial comparing Enhertu with a positive control drug. Data from this trial supportedEnhertu as the New Standard of Care for These HER2-Positive Breast Cancer PatientsThe potential.
Data presented at the ESMO Congress showed that the DESTINY-Breast03 trial met its primary endpoint of progression-free survival (PFS) in a pre-specified interim analysis:Compared with Kadcyla, Enhertu significantly reduced the risk of disease progression or death by 72%.(HR=0.28; 95%CI:0.22-0.37; p=7.8x10E-22). After follow-ups of 15.5 months for the Enhertu group and 13.9 months for the Kadcyla group, the median PFS for patients in the Enhertu group has not yet been reached (95%CI:18.5-NE), while the median PFS for patients in the Kadcyla group was 6.8 months (95%CI:5.6-8.2).
In terms of the key secondary endpoint of investigator-assessed PFS,The median PFS in the Enhertu group was 3 times that of the Kadcyla group (25.1 months vs 7.2 months).; HR=0.26; 95% CI: 0.20-0.35; p=6.5x10E-24). Consistent PFS benefits were observed in key subgroups of patients treated with Enhertu, including those with a history of stable brain metastases.
Moreover, in terms of the key secondary endpoint, overall survival (OS):Compared with the Kadcyla group, the Enhertu group showed a strong trend of OS improvement (HR=0.56).; 95% CI: 0.36-0.86; nominal p=0.007172), but this analysis is not yet mature and lacks statistical significance. After one year, nearly all patients in the Enhertu group survived (94.1%), compared to 85.9% in the Kadcyla group.
Compared with the Kadcyla group, the Enhertu group confirmedObjective Response Rate (ORR) more than doubled (79.7% vs 34.2%)In the Enhertu group, 42 cases (16.1%) of complete response (CR) and 166 cases (63.6%) of partial response (PR) were observed, while in the Kadcyla group, 23 cases (8.7%) of complete response (CR) and 67 cases (25.5%) of partial response (PR) were observed.
In the trial, the safety profile of Enhertu was consistent with previous findings.Clinical TrialConsistent, no new safety issues were identified. The most common ≥3 grade treatment-emergent adverse events in the Enhertu group were neutropenia (19.1%), thrombocytopenia (7.0%), leukopenia (6.6%), and nausea (6.6%).
DESTINY-Breast03 Trial Results
In March 2019, AstraZeneca and Daiichi Sankyo reached a $6.9 billion immunotherapy agreement.TumorCollaborate to jointly develop Enhertu for the treatment of various cancer patients with different HER2 expression levels or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and HER2-low breast cancer.
Enhertu is a next-generation ADC drug that links the HER2-targeted humanized monoclonal antibody trastuzumab (Herceptin) with a novel topoisomerase 1 inhibitor exatecan derivative (DX-8951 derivative, DXd) through a 4-peptide linker, enabling targeted delivery of cytotoxic agents into cancer cells and reducing systemic exposure to cytotoxic agents compared with conventional chemotherapy.
To date, Enhertu (5.4mg/kg) has been approved in multiple countries as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting. Additionally, Enhertu (6.4mg/kg) has also been approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have previously received a trastuzumab-based regimen.
Breast cancer is the most common type of cancer in women and one of the leading causes of cancer-related deaths in women. Approximately 20% of breast cancer cases are HER2-positive. Despite recent advancements in treatment and the approval of several new drugs, there remains a significant unmet clinical need in patients with HER2-positive metastatic breast cancer. This disease is still incurable, and patients eventually experience disease progression after receiving currently available therapies. HER2 is a tyrosine kinase receptor growth-promoting protein expressed on variousTumorCell surface, including gastric cancer, breast cancer, lung cancer, and colorectal cancer, is associated with invasive disease and poor prognosis. (Bioon.com)