Datopotamab Deruxtecan Application in the EU for Patients with Advanced Nonsquamous Non-Small Cell Lung Cancer Voluntarily Withdrawn
AstraZeneca (AZN) and Daiichi Sankyo have voluntarily withdrawn their marketing authorization application (MAA) in the EU for datopotamab deruxtecan (Dato-DXd) for treating advanced nonsquamous non-small cell lung cancer (NSCLC). The withdrawal follows feedback from the European Medicines Agency's Committee for Medicinal Products for Human Use.
The companies remain committed to developing the drug for lung cancer patients through seven pivotal trials. Their separate application for datopotamab deruxtecan in hormone receptor positive, HER2 negative metastatic breast cancer remains under EU review.
AstraZeneca (AZN) e Daiichi Sankyo hanno ritirato volontariamente la loro domanda di autorizzazione alla commercializzazione (MAA) nell'UE per il datopotamab deruxtecan (Dato-DXd) per il trattamento del carcinoma polmonare non a piccole cellule (NSCLC) avanzato, non squamoso. Il ritiro è avvenuto a seguito di un feedback del Comitato per i Medicinali per Uso Umano dell'Agenzia Europea dei Medicinali.
Le aziende rimangono impegnate nello sviluppo del farmaco per i pazienti affetti da cancro ai polmoni attraverso sette studi pivotal. La loro domanda separata per il datopotamab deruxtecan in cancro mammario metastatico positivo ai recettori ormonali e negativo per HER2 è attualmente in fase di revisione da parte dell'UE.
AstraZeneca (AZN) y Daiichi Sankyo han retirado voluntariamente su solicitud de autorización de comercialización (MAA) en la UE para el datopotamab deruxtecan (Dato-DXd) para tratar el cáncer de pulmón no microcítico avanzado (NSCLC) no escamoso. La retirada se produce tras los comentarios del Comité de Medicamentos para Uso Humano de la Agencia Europea de Medicamentos.
Las empresas siguen comprometidas con el desarrollo del fármaco para los pacientes con cáncer de pulmón a través de siete ensayos pivotal. Su solicitud separada para el datopotamab deruxtecan en cáncer de mama metastásico positivo para receptores hormonales y negativo para HER2 sigue en revisión en la UE.
AstraZeneca (AZN)와 Daiichi Sankyo가 고급 비편평 비세포 폐암(NSCLC) 치료를 위한 datopotamab deruxtecan(Dato-DXd)의 EU 마케팅 허가 신청(MAA)을 자발적으로 철회했습니다. 철회는 유럽 의약품청(European Medicines Agency)의 인체를 위한 의약품 심사 위원회의 피드백에 따른 것입니다.
이들 기업은 7개의 주요 임상 시험을 통해 폐암 환자를 위한 약물 개발에 최선을 다하고 있습니다. 호르몬 수용체 양성, HER2 음성 전이성 유방암에 대한 datopotamab deruxtecan의 별도 신청은 EU에서 심사 중입니다.
AstraZeneca (AZN) et Daiichi Sankyo ont retiré volontairement leur demande d'autorisation de mise sur le marché (MAA) dans l'UE pour le datopotamab deruxtecan (Dato-DXd) pour le traitement du cancer du poumon non à petites cellules (NSCLC) avancé non squameux. Ce retrait fait suite aux retours du Comité des médicaments à usage humain de l'Agence européenne des médicaments.
Les entreprises restent engagées à développer le médicament pour les patients atteints de cancer du poumon à travers sept essais cliniques majeurs. Leur demande séparée pour le datopotamab deruxtecan dans le cadre d'un cancer du sein métastatique positif aux récepteurs hormonaux et négatif à HER2 est toujours en cours d'examen par l'UE.
AstraZeneca (AZN) und Daiichi Sankyo haben ihren Marketing-Autorisierungsantrag (MAA) in der EU für datopotamab deruxtecan (Dato-DXd) zur Behandlung von fortgeschrittenem nicht-squamösem nicht-kleinzelligem Lungenkrebs (NSCLC freiwillig zurückgezogen. Der Rückzug erfolgt nach Rückmeldungen des Ausschusses für Humanarzneimittel der Europäischen Arzneimittel-Agentur.
Die Unternehmen bleiben jedoch weiterhin verpflichtet, das Medikament durch sieben entscheidende Studien für Lungenkrebspatienten zu entwickeln. Ihr separater Antrag für datopotamab deruxtecan bei hormonrezeptorpositivem, HER2-negativem metastasiertem Brustkrebs befindet sich weiterhin in der Prüfung durch die EU.
- Application for breast cancer indication remains under review in EU
- Seven pivotal trials ongoing in various lung cancer settings
- Withdrawal of EU marketing authorization application for NSCLC indication
- Regulatory setback following EMA committee feedback
Insights
The withdrawal of datopotamab deruxtecan's MAA in the EU for NSCLC represents a significant setback for AstraZeneca and Daiichi Sankyo. This ADC targeting TROP2 was positioned to compete in the lucrative $24 billion NSCLC market. The EMA's feedback leading to withdrawal suggests potential concerns with either efficacy data or risk-benefit profile from the TROPION-Lung01 trial.
Think of this like a racing car failing its technical inspection before a major race - while the car can be improved and brought back, it means missing out on valuable track time and potential victories. The companies will need to address the EMA's concerns, which could require additional data or analyses, potentially delaying EU market entry by 12-24 months.
The ongoing review for breast cancer indication and seven pivotal trials in lung cancer settings provide multiple shots on goal, but this withdrawal could impact market confidence in the broader datopotamab deruxtecan program. The NSCLC market is increasingly competitive with other ADCs and novel therapeutics in development.
The voluntary withdrawal will likely pressure AstraZeneca's stock in the near term, as datopotamab deruxtecan was expected to be a key growth driver. Market estimates projected potential peak sales of $2.5-4 billion for the NSCLC indication in the EU. This setback could result in a 3-5% downward revision in consensus revenue forecasts for 2025-2026.
However, AstraZeneca's diverse oncology portfolio and the pending breast cancer indication provide some cushion. The company's market cap of
The decision to withdraw the MAA was informed by feedback from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA). Daiichi Sankyo and AstraZeneca will continue to work to bring datopotamab deruxtecan to patients with lung cancer in the EU who can benefit and are committed to unlocking the potential of this medicine in lung cancer through our robust clinical development program which includes seven pivotal trials in various lung cancer settings.
Datopotamab deruxtecan is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by Daiichi Sankyo and AstraZeneca.
Daiichi Sankyo and AstraZeneca’s application in the EU for datopotamab deruxtecan for the treatment of hormone receptor (HR) positive, HER2 negative metastatic breast cancer based on the TROPION-Breast01 phase 3 trial remains under review.
About TROPION-Lung01
TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of datopotamab deruxtecan versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
The dual primary endpoints of TROPION-Lung01 are progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, and disease control rate as assessed by both BICR and investigator, and safety.
TROPION-Lung01 enrolled approximately 600 patients in
Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology in September 2024.
About Advanced Non-Small Cell Lung Cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.1 In
TROP2 is a protein broadly expressed in the majority of NSCLC tumors.6 There is currently no TROP2 directed ADC approved for the treatment of lung cancer.7,8
About Datopotamab Deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Additional regulatory submissions in breast cancer are under review in
Datopotamab deruxtecan has been granted Breakthrough Therapy Designation by the
About the Datopotamab Deruxtecan Clinical Development Program
A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple negative breast cancer and HR positive, HER2 low or negative breast cancer. The program includes seven phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating datopotamab deruxtecan as a monotherapy and in combination with other anticancer treatments in various settings.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and datopotamab deruxtecan in July 2020, except in
About the ADC Portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo.
The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc.,
The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com.
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References
1 World Health Organization. Global Cancer Observatory: Lung. Accessed December 2024.
2 American Cancer Society. Key Statistics for Lung Cancer. Accessed December 2024.
3 Chen R, et al. J Hematol Oncol. 2020:13(1):58.
4 Majeed U, et al. J Hematol Oncol. 2021;14(1):108.
5 Pircher A, et al. Anticancer Research. 2020;70(5):287-294.
6 Mito R, et al. Pathol Int. 2020;70(5):287-294.
7 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer. Accessed December 2024.
8 Rodríguez-Abreau D, et al. Ann Onc. 2021 Jul;32(7): 881-895.
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Media Contacts
Global/US:
Jennifer Brennan
Daiichi Sankyo, Inc.
jennifer.brennan@daiichisankyo.com
+1 908 900 3183 (mobile)
EU:
Natalia Juncal Strandt
Daiichi Sankyo Europe GmbH
natalia.juncalstrandt@daiichisankyo.com
+49 (151) 16817622 (mobile)
Daiichi Sankyo Co., Ltd.
DS-PR@daiichisankyo.co.jp
Investor Relations Contact:
DaiichiSankyoIR_jp@daiichisankyo.com
Source: Daiichi Sankyo
FAQ
Why did AZN withdraw the EU application for datopotamab deruxtecan in lung cancer?
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