第一三共与阿斯利康宣布Enhertu（德曲妥珠单抗）的新适应症上市申请获欧洲药品管理局（EMA）受理

• Submission based on DESTINY-Breast06 phase 3 trial results that showed Daiichi Sankyo andAstraZeneca’s ENHERTU demonstrated a statistically significant and clinically meaningfulimprovement in progression-free survival compared to standard of care chemotherapy 

About DESTINY-Breast06 

DESTINY-Breast06 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety ofENHERTU (5.4 mg/kg) versus investigator’s choice of chemotherapy (capecitabine, paclitaxel or nabpaclitaxel) in patients with HR positive, HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow(defined as IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had noprior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrinetherapy in the metastatic setting. Patients also were eligible if they had received one prior line of endocrinetherapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progressionwithin six months of starting first-line treatment or received endocrine therapy as an adjuvant treatment andexperienced disease recurrence within 24 months.

The primary endpoint is progression-free survival (PFS) in the HR positive, HER2 low patient population asmeasured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR inthe overall trial population (HER2 low and HER2 ultralow), overall survival (OS) in patients in the HER2low patient population and OS in the overall trial population. Other secondary endpoints include objectiveresponse rate, duration of response, time to first subsequent treatment or death, time to second subsequenttreatment or death and safety. Analysis of the HER2 ultralow subgroup was not powered to demonstratestatistical significance. 

DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and n=153 for HER2 ultralow) at multiplesites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visitClinicalTrials.gov.

About Breast Cancer and HER2 Expression 

Breast cancer is the second most common cancer and one of the leading causes of cancer-related deathsworldwide.1 More than two million breast cancer cases were diagnosed in 2022 with more than 665,000deaths globally.1 In Europe, approximately 557,000 cases of breast cancer are diagnosed annually.2 Whilesurvival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosedwith or who progress to metastatic disease are expected to live five years following diagnosis.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types oftumors, including breast cancer.4 Patients with high levels of HER2 expression (IHC 3+ or IHC2+/ISH+) areclassified as HER2 positive and treated with HER2 targeted therapies, representing approximately 15 to 20%percent of all breast cancers.5 Historically, tumors that were not classified as HER2 positive were classifiedas HER2 negative, despite the fact that many of these tumors still carry some level of HER2 expression.6 It isestimated that approximately 60% to 65% of HR positive, HER2 negative breast cancers are HER2 low andpotentially an additional 25% may be HER2 ultralow.7,8

Endocrine therapies are widely given consecutively in the early lines of treatment for HR positive metastaticbreast cancer.9 However, following two lines of endocrine therapy, further efficacy with additional endocrinetreatment is often limited.9 The current standard of care following endocrine therapy is chemotherapy, whichis associated with poor response rates and outcomes.9,10,11,12 

Prior to the approval of ENHERTU following chemotherapy in HER2 low metastatic breast cancer based onthe DESTINY-Breast04 trial, there were no targeted therapies approved specifically for patients with HER2low expression.13 There are no targeted therapies specifically approved for patients with HER2 ultralowexpression.14

About ENHERTU 

ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directedADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ENHERTU is the lead ADC inthe oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientificplatform. ENHERTU consists of a HER2 monoclonal antibody attached to a number of topoisomerase Iinhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patientswith unresectable or metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+) breast cancer whohave received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant oradjuvant setting, and have developed disease recurrence during or within six months of completing therapybased on the results from the DESTINY-Breast03 trial. 

ENHERTU (5.4 mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patientswith unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a priorsystemic therapy in the metastatic setting or developed disease recurrence during or within six months ofcompleting adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.ENHERTU (5.4 mg/kg) is approved in more than 35 countries worldwide for the treatment of adult patientswith unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations, as detectedby a locally or regionally approved test, and who have received a prior systemic therapy based on the resultsfrom the DESTINY-Lung02 trial. 

Continued approval in the U.S. for this indication may be contingent uponverification and description of clinical benefit in a confirmatory trial.

ENHERTU (6.4 mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patientswith locally advanced or metastatic HER2 positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the resultsfrom the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Full approval inChina for this indication will depend on whether a randomized controlled confirmatory clinical trial candemonstrate clinical benefit in this population. 

ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of adult patients with unresectable ormetastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have nosatisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02,DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the U.S. may becontingent upon verification and description of clinical benefit in a confirmatory trial.

About the ENHERTU Clinical Development Program 

A comprehensive global clinical development program is underway evaluating the efficacy and safety ofENHERTU monotherapy across multiple HER2 targetable cancers. Trials in combination with otheranticancer treatments, such as immunotherapy, also are underway. 

About the Daiichi Sankyo and AstraZeneca Collaboration 

Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercializeENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyomaintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply ofENHERTU and datopotamab deruxtecan.

About the DXd ADC Portfolio of Daiichi Sankyo 

The DXd ADC portfolio of Daiichi Sankyo currently consists of six ADCs in clinical development acrossmultiple types of cancer. ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan (Dato-DXd), aTROP2 directed ADC, are being jointly developed and commercialized globally with AstraZeneca.Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed andcommercialized globally with Merck & Co., Inc., Rahway, N.J. USA. DS-3939, a TA-MUC1 directed ADC,is being developed by Daiichi Sankyo. 

Designed using Daiichi Sankyo’s proprietary DXd ADC Technology to target and deliver a cytotoxicpayload inside cancer cells that express a specific cell surface antigen, each ADC consists of a monoclonalantibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) viatetrapeptide-based cleavable linkers.

Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan andDS-3939 are investigational medicines that have not been approved for any indication in any country. Safetyand efficacy have not been established.

About Daiichi Sankyo 

Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development ofsociety that discovers, develops and delivers new standards of care to enrich the quality of life around theworld. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science andtechnology to create new modalities and innovative medicines for people with cancer, cardiovascular andother diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.