TOKYO & MUNICH--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) ENHERTU® (trastuzumab deruxtecan) has been approved successful the European Union (EU) arsenic a monotherapy for the attraction of big patients with precocious HER2 affirmative gastric oregon gastroesophageal junction (GEJ) adenocarcinoma who person received a anterior trastuzumab-based regimen.
ENHERTU is simply a specifically engineered HER2 directed antibody cause conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
Approximately 136,000 cases of gastric crab are diagnosed annually successful Europe, wherever it represents the sixth starring origin of crab death.1,2 Gastric crab is typically diagnosed successful the precocious stage, and adjacent erstwhile the illness is diagnosed astatine earlier stages, the endurance complaint remains modest.3,4 Approximately 1 successful 5 gastric cancers are HER2 positive.5,6
The support by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use successful November 2022 and is based connected results from the DESTINY-Gastric02 and DESTINY-Gastric01 signifier 2 trials.
“Today’s quality is simply a invited beforehand for patients with HER2 affirmative precocious gastric cancer,” said Eric Van Cutsem, MD, PhD, Head of Department of Oncology, University of Leuven, Belgium and Founding Chair of the ESMO-GI/World Congress of Gastrointestinal Cancers. “Patients with this illness look mediocre outcomes pursuing progression connected archetypal attraction with a HER2 directed medicine arsenic galore bash not respond to further treatment, and adjacent those that bash respond often bash not person durable responses. Data from the DESTINY-Gastric02 and DESTINY-Gastric01 trials enactment ENHERTU becoming a caller modular of attraction for patients successful this setting.”
In DESTINY-Gastric02, which enrolled patients from Europe and North America, attraction with ENHERTU (6.4 mg/kg) resulted successful a confirmed nonsubjective effect complaint (ORR) of 41.8% (95% assurance interval [CI]: 30.8-53.4) arsenic assessed by autarkic cardinal reappraisal (ICR). Median duration of effect (DoR) was 8.1 months (95% CI: 5.9-NE).
In DESTINY-Gastric01, which enrolled patients from Japan and South Korea, attraction with ENHERTU resulted successful a confirmed ORR of 40.5% versus 11.3% with chemotherapy (irinotecan oregon paclitaxel) arsenic assessed by ICR. The median DoR was 11.3 months with ENHERTU versus 3.9 months with chemotherapy. Patients treated with ENHERTU had a 41% simplification successful the hazard of decease versus patients treated with chemotherapy (hazard ratio [HR] = 0.59; 95% CI: 0.39-0.88, p=0.0097) with a median OS of 12.5 months (95% CI: 9.6-14.3) versus 8.4 months (95% CI: 6.9-10.7).
“ENHERTU is the archetypal antibody cause conjugate to beryllium approved successful Europe for precocious gastric cancer, representing a large beforehand successful treating this difficult-to-treat cancer,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “With this approval, we tin present connection patients with antecedently treated HER2 affirmative gastric crab a attraction with clinically meaningful efficacy.”
“Today’s important support makes ENHERTU the archetypal HER2 directed medicine to beryllium approved for gastric crab successful the European Union successful much than a decade,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “Patients crossed the EU with precocious HER2 affirmative illness who person progressed pursuing attraction successful the first-line mounting whitethorn present person the imaginable accidental to payment from attraction with ENHERTU.”
In some trials, the information profiles observed successful patients treated with ENHERTU were accordant with those seen successful different trials of ENHERTU with nary caller information signals identified. Grade 3 oregon people 4 treatment-related adverse events from a pooled information investigation of patients treated with ENHERTU (6.4 mg/kg) crossed aggregate tumor types successful objective studies included neutropenia (27.9%), anemia (23.1%), leukopenia (12.9%), thrombocytopenia (9.0%), fatigue (8.2%), decreased appetite (8.1%), lymphopenia (7.4%), nausea (5.8%), accrued transaminases (4.7%), hypokalemia (4.2%), pneumonia (2.9%), febrile neutropenia (2.9%), vomiting (2.4%), diarrhea (2.1%), decreased value (2.1%), accrued humor alkaline phosphate (1.8%), interstitial lung illness (ILD) (1.6%), dyspnea (1.3%) and alteration ejection fraction (1.1%). Grade 5 treatment-related events occurred successful 2.6% of patients including ILD (1.9%).
Financial Considerations
Following support successful the EU, an magnitude of $35 cardinal is owed from AstraZeneca to Daiichi Sankyo arsenic a second-line milestone outgo successful HER2 affirmative metastatic gastric cancer. Sales of ENHERTU successful astir EU territories are recognized by Daiichi Sankyo. For further details connected the fiscal arrangements, delight consult the collaboration statement from March 2019.
About DESTINY-Gastric02
DESTINY-Gastric02 is an open-label, single-arm signifier 2 proceedings successful patients evaluating the efficacy and information of ENHERTU (6.4 mg/kg) successful patients with HER2 affirmative metastatic and/or unresectable gastric oregon GEJ adenocarcinoma with illness progression connected oregon aft a trastuzumab-containing regimen.
The superior endpoint of DESTINY-Gastric02 is confirmed ORR based connected ICR. Secondary endpoints see progression-free endurance (PFS), OS, DoR and safety. Primary results from the DESTINY-Gastric02 signifier 2 proceedings were presented astatine the European Society for Medical Oncology (ESMO) Congress 2021 with updated information presented astatine 2022 ESMO.
DESTINY-Gastric02 enrolled 79 patients astatine aggregate sites successful North America and Europe. For much accusation astir the trial, sojourn ClinicalTrials.gov.
About DESTINY-Gastric01
DESTINY-Gastric01 is simply a randomized, open-label signifier 2 proceedings evaluating the efficacy and information of ENHERTU (6.4 mg/kg) successful patients with chiefly HER2 affirmative (defined arsenic immunohistochemistry (IHC) 3+ oregon IHC 2+/in-situ hybridization (ISH)+) precocious gastric crab oregon GEJ adenocarcinoma with illness progression pursuing 2 oregon much anterior attraction regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to person ENHERTU oregon physician’s prime of chemotherapy (paclitaxel oregon irinotecan monotherapy).
The superior endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints see OS, PFS, DoR, illness power complaint and clip to attraction nonaccomplishment arsenic good arsenic pharmacokinetic and information endpoints. The superior investigation was published successful The New England Journal of Medicine with updated information presented astatine the 2021 American Society of Clinical Oncology Annual Meeting.
DESTINY-Gastric01 enrolled 187 patients astatine aggregate sites successful Japan and South Korea. For much accusation astir the trial, sojourn ClinicalTrials.gov.
About HER2 Positive Gastric Cancer
Gastric (stomach) crab is the 5th astir communal crab worldwide and the 4th highest starring origin of crab mortality, with a five-year planetary endurance complaint of 5% to 10% for precocious oregon metastatic disease.3,7,8 Approximately 1 cardinal caller patients were diagnosed with gastric crab successful 2020, with 768,000 deaths reported globally.2 In Europe, astir 136,000 cases of gastric crab are diagnosed annually, and Eastern Europe has the 2nd highest incidence of gastric crab worldwide aft Eastern Asia.2,8 Gastric crab is the sixth starring origin of crab decease successful Europe and is typically diagnosed successful the precocious stage, and adjacent erstwhile diagnosed successful earlier stages of the disease, the endurance complaint remains modest.1,3,4
Approximately 1 successful 5 gastric cancers are HER2 positive.5,6 HER2 is simply a tyrosine kinase receptor maturation promoting macromolecule expressed connected the aboveground of galore types of tumors including breast, gastric, lung and colorectal cancers.5 HER2 overexpression whitethorn beryllium associated with a circumstantial HER2 cistron alteration known arsenic HER2 amplification.6
Recommended first-line attraction successful the EU for HER2 affirmative precocious oregon metastatic gastric crab is operation chemotherapy positive trastuzumab, an anti-HER2 medicine, which has been shown to amended endurance outcomes erstwhile added to chemotherapy.9,10 For patients with metastatic gastric crab that progresses pursuing archetypal attraction with a trastuzumab-based regimen, determination were antecedently nary different approved HER2 directed medicines successful the EU anterior to the support of ENHERTU.7,11,12
About ENHERTU
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki successful the U.S. only) is simply a HER2 directed ADC. Designed utilizing Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the pb ADC successful the oncology portfolio of Daiichi Sankyo and the astir precocious programme successful AstraZeneca’s ADC technological platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a unchangeable tetrapeptide-based cleavable linker.
ENHERTU (5.4 mg/kg) is approved successful much than 40 countries for the attraction of big patients with unresectable oregon metastatic HER2 affirmative bosom crab who person received a (or 1 oregon more) anterior anti-HER2-based regimen, either successful the metastatic mounting oregon successful the neoadjuvant oregon adjuvant setting, and person developed illness recurrence during oregon wrong six months of completing therapy, based connected the results from the DESTINY-Breast03 trial. ENHERTU besides is approved successful respective countries for the attraction of big patients with unresectable oregon metastatic HER2 affirmative bosom crab who person received 2 oregon much anterior anti-HER2-based regimens based connected the results from the DESTINY-Breast01 trial.
ENHERTU (5.4 mg/kg) is approved successful Brazil and the U.S. for the attraction of big patients with unresectable oregon metastatic HER2 debased (IHC 1+ oregon IHC 2+/ISH-) bosom crab who person received a anterior systemic therapy successful the metastatic mounting oregon developed illness recurrence during oregon wrong six months of completing adjuvant chemotherapy based connected the results from the DESTINY-Breast04 trial.
ENHERTU (5.4 mg/kg) is approved nether accelerated support successful the U.S. for the attraction of big patients with unresectable oregon metastatic non-small compartment lung crab (NSCLC) whose tumors person activating HER2 (ERBB2) mutations, arsenic detected by an FDA-approved test, and who person received a anterior systemic therapy, based connected the results of the DESTINY-Lung02 trial. Continued support for this denotation whitethorn beryllium contingent upon verification and statement of objective payment successful a confirmatory trial.
ENHERTU (6.4 mg/kg) is approved successful respective countries for the attraction of big patients with locally precocious oregon metastatic HER2 affirmative gastric oregon gastroesophageal junction (GEJ) adenocarcinoma who person received a anterior trastuzumab-based regimen based connected the results from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trial.
About the ENHERTU Clinical Development Program
A broad planetary improvement programme is underway evaluating the efficacy and information of ENHERTU monotherapy crossed aggregate HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials successful operation with different anticancer treatments, specified arsenic immunotherapy, besides are underway.
Regulatory applications for ENHERTU successful breast, non-small compartment lung and gastric cancers are presently nether reappraisal successful respective countries.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a planetary collaboration to jointly make and commercialize ENHERTU successful March 2019 and datopotamab deruxtecan (Dato-DXd) successful July 2020, but successful Japan wherever Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is liable for the manufacturing and proviso of ENHERTU and datopotamab deruxtecan.
About the DXd ADC Portfolio of Daiichi Sankyo
The DXd ADC portfolio of Daiichi Sankyo presently consists of 5 ADCs successful objective improvement crossed aggregate types of cancer. The company’s objective proceedings signifier DXd ADCs see ENHERTU, a HER2 directed ADC and datopotamab deruxtecan (Dato-DXd), a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca; and, patritumab deruxtecan (HER3-DXd), a HER3 directed ADC. Two further ADCs including ifinatamab deruxtecan (I-DXd; DS-7300), a B7-H3 directed ADC, and DS-6000, a CDH6 directed ADC, are being developed done a strategical early-stage probe collaboration with Sarah Cannon Research Institute.
Each ADC is designed utilizing Daiichi Sankyo’s proprietary DXd ADC exertion to people and present a cytotoxic payload wrong crab cells that explicit a circumstantial compartment aboveground antigen. Each ADC consists of a monoclonal antibody attached to a fig of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan and DS-6000 are investigational medicines that person not been approved for immoderate denotation successful immoderate country. Safety and efficacy person not been established.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating caller modalities and innovative medicines by leveraging our world-class subject and exertion for our intent “to lend to the enrichment of prime of beingness astir the world.” In summation to our existent portfolio of medicines for crab and cardiovascular disease, Daiichi Sankyo is chiefly focused connected processing caller therapies for radical with crab arsenic good arsenic different diseases with precocious unmet aesculapian needs. With much than 100 years of technological expertise and a beingness successful much than 20 countries, Daiichi Sankyo and its 16,000 employees astir the satellite gully upon a affluent bequest of innovation to recognize our 2030 Vision to go an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For much information, delight sojourn www.daiichisankyo.com.
References:
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2 WHO. Stomach Cancer Fact Sheet. Accessed December 2022.
3 SEER Cancer Stat Facts: Stomach Cancer 2012-2018. Accessed December 2022.
4 Cancer Research UK. Stomach Cancer Survival Statistics. Accessed December 2022.
5 Iqbal N, et al. Mol Biol Int. 2014; 2014:852748.
6 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-4625.
7 Casamayor M, et al. Ecancermedicalscience. 2018;12:883.
8 Sung H, et al. Ca Cancer J Clin. 2021;71:209–249.
9 Oditura M, et al. World J Gastroenterol. 2014 Feb 21;20(7):1635-49.
10 Lordick F, et al. Ann Oncol. 2022; 33(10):1012.
11 Thuss-Patience PC, et al. Lancet Oncol. 2017;18(5):640-653.
12 Satoh T, et al. J Clin Oncol. 2014;32(19):2039‐2049.
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