DAIICHI-SANKYO
Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/Nasdaq: AZN) ENHERTU® (trastuzumab deruxtecan) has been approved in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.
ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca.
The approval by the European Commission (EC) follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the DESTINY-Breast03 phase 3 trial, which were published in The New England Journal of Medicine . In the DESTINY-Breast03 trial, 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<0.000001) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The median progression-free survival (PFS) for patients treated with ENHERTU was not reached (95% CI: 18.5-NE) compared to 6.8 months for T-DM1 (95% CI: 5.6-8.2), as assessed by blinded independent central review (BICR).
In Europe, more than 530,000 patients are diagnosed with breast cancer each year.1 Approximately one in five patients with breast cancer are considered HER2 positive.2 Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4
“This approval is an important milestone for patients and clinicians in Europe, since previously treated patients with HER2 positive metastatic breast cancer typically experience disease progression in less than a year with historical standard of care treatment,” said Javier Cortés, MD, PhD, Head, International Breast Cancer Center (IBCC), Barcelona, Spain. “In the DESTINY-Breast03 trial, the time to progression was extended well beyond a year for patients receiving ENHERTU, illustrating the potential for this medicine to set a new benchmark in the treatment of HER2 positive metastatic breast cancer.”
Additional results from the DESTINY-Breast03 phase 3 trial showed that in the secondary endpoint of overall survival (OS), there was a strong trend towards improved OS with ENHERTU (HR=0.55; 95% CI: 0.36-0.86), however this analysis is not yet mature and further follow-up is ongoing. Nearly all patients treated with ENHERTU were alive at nine months (96.1%; 95% CI: 92.8-97.9) compared to 91.3% of patients treated with T-DM1 (95% CI: 87.1-94.2). Confirmed objective response rate (ORR) was more than doubled in the ENHERTU arm versus the T-DM1 arm (79.7% [n=208; 95% CI: 74.3-84.4] versus 34.2% [n=90; 95% CI: 28.5-40.3]).
The safety of ENHERTU has been evaluated in a pooled analysis of 573 patients across multiple tumor types who had received at least one dose of ENHERTU (5.4 mg/kg) in clinical studies. The median duration of treatment with ENHERTU was 11.3 months (range 0.7-37.9 months). The most common adverse reactions were nausea (77.0%), fatigue (57.2%), vomiting (46.8%), alopecia (38.0%), neutropenia (34.6%), constipation (33.9%), decreased appetite (33.7%), anemia (32.3%), diarrhea (30.7%), musculoskeletal pain (27.4%), transaminases increased (24.4%), leukopenia (24.1%), thrombocytopenia (23.0%), and upper respiratory tract infection (22.7%).
Cases of interstitial lung disease (ILD) or pneumonitis were reported in 12.0% of patients. Most ILD cases were grade 1 (2.6%) and grade 2 (7.3%). Grade 3 cases occurred in 0.7% of patients, no grade 4 cases occurred and grade 5 cases occurred in 1.4% of patients. Patients should be advised to immediately report cough, dyspnea (shortness of breath), fever and/or any new worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD or pneumonitis and those with suspected ILD or pneumonitis should be evaluated by radiographic imaging, preferably a computed tomography (CT) scan. Patients with a history of ILD or pneumonitis may be at increased risk.
“We believe there is a significant need to transform outcomes for patients with HER2 positive metastatic breast cancer in Europe,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “In DESTINY-Breast03, treatment with ENHERTU demonstrated superior progression-free survival and a doubling of the response rate compared to another HER2 directed ADC. With this approval we are now able to offer patients with HER2 positive metastatic breast cancer another option earlier in their treatment.”
“With this approval, patients across Europe with HER2 positive metastatic breast cancer will have the opportunity to be treated with ENHERTU even earlier in the treatment of their disease, improving their chance for better outcomes beyond what we can already offer patients treated in later line settings,” said Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca. “Today’s news is a further step in achieving our vision to continuously bring the transformative potential of ENHERTU to patients as early as possible in their treatment to improve cancer outcomes.”
Based on the results of DESTINY-Breast03, the European Society for Medical Oncology Clinical Practice Guidelines were updated in October 2021 to recommend ENHERTU for use as the preferred second-line therapy for patients with HER2 positive metastatic breast cancer following progression with a taxane and trastuzumab.5
As part of this approval, the EC has also extended the market protection period for ENHERTU in this setting by one extra year based on the significant clinical benefit compared to existing approved therapies.
Financial Considerations
Following approval in the EU, an amount of $75 million is due from AstraZeneca to Daiichi Sankyo as a second-line milestone payment in HER2 positive metastatic breast cancer. For further details on the financial arrangements, please consult the collaboration agreement from March 2019 .
About DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. The primary efficacy endpoint of DESTINY-Breast03 is PFS based on blinded independent central review. Overall survival (OS) was a key secondary efficacy outcome measure. Secondary endpoints included ORR, duration of response and PFS based on investigator assessment. DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America. Results from DESTINY-Breast03 have been published in The New England Journal of Medicine . For more information about the trial, visit ClinicalTrials.gov .
About HER2 Positive Breast Cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.6 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.6 In Europe, more than 530,000 patients are diagnosed with breast cancer each year.1 Approximately one in five patients with breast cancer are considered HER2 positive.2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8
Despite initial treatment with trastuzumab, pertuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.3,4
About ENHERTU
ENHERTU (trastuzumab deruxtecan, fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received a (or one or more) 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, based on the results from the DESTINY-Breast03 trial. ENHERTU also is approved in several countries 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 based on the results from the DESTINY-Breast01 trial.
ENHERTU (6.4 mg/kg) is 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 received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Regulatory applications for ENHERTU are currently under review in China, Japan and several other countries for the treatment of adult patients with HER2 positive unresectable or metastatic breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.
ENHERTU is under review in Europe and Japan for the treatment of adult patients with unresectable or metastatic HER2 low (immunohistochemistry (IHC) 1+ or IHC 2+/in-situ hybridization (ISH)-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results from the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer must additionally have received or be ineligible for endocrine therapy.
ENHERTU also is currently under review in the U.S. for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have a HER2 (ERBB2) mutation and who have received a prior systemic therapy based on the results from the DESTINY-Lung01 and DESTINY-Lung02 trials, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.
ENHERTU recently was granted Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results of the DESTINY-Breast04 trial. Patients with HR positive breast cancer should additionally have received or be ineligible for endocrine therapy.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialize trastuzumab deruxtecan in March 2019 and datopotamab deruxtecan (Dato-DXd) in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan and datopotamab deruxtecan.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit www.daiichisankyo.com .
____________________________
References:
1
Globocan 2020. Europe Fact Sheets
. Last accessed: June 2022.
2
Ahn S, et al. J Pathol Transl Med
. 2020;54(1):34-44.
3
Barok M, et al. Breast Cancer Res
. 2014;16(2):209.
4
Nader-Marta G, et al. ESMO Open
. 2022; 7:1.
5
Gennari A, et al. Ann Oncol
.
2021; 32(12):1475-1495.
6
Sung H, et al. CA Cancer J Clin
. 2021; 10.3322/caac.21660.
7
Iqbal N, et al. Mol Biol Int
. 2014;852748.
8
Pillai R, et al. Cancer
.
2017;1;123(21):4099-4105.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220718005714/en/
Link:
About Business Wire
Subscribe to releases from Business Wire
Subscribe to all the latest releases from Business Wire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from Business Wire
Access Advance Welcomes Global Technology Leaders as Licensees and Licensors to New Video Distribution Patent Pool2.7.2025 02:00:00 CEST | Press release
Access Advance LLC ("Advance") today announced the inaugural roster of licensees and licensors for its Video Distribution Patent ("VDP") Pool, marking a significant milestone in the program's rapid market adoption since its January announcement. The participation of major global companies heavily involved in video codec technology demonstrates strong industry support for the comprehensive licensing solution covering HEVC, VVC, VP9, and AV1 codecs. The VDP Pool has successfully attracted a group of licensees/licensors including ByteDance, Kuaishou, NTT Docomo, and Tencent. This represents the beginning of what Access Advance expects to be widespread adoption among content streaming providers seeking simplified codec licensing. The licensees’ participation provides immediate access to the wide-ranging patent portfolio while benefiting from the fixed tiered pricing structure designed to scale with business size. "We're pleased to welcome ByteDance, Kuaishou, NTT Docomo and Tencent as our
Intralot S.A. to Acquire Bally’s International Interactive Business in a Transaction that Creates a Global Gaming Technology and Services Company in Lottery and Digital Online Gaming Markets1.7.2025 21:10:00 CEST | Press release
Intralot S.A. to Remain Listed on the Athens Stock ExchangeTransaction Enterprise Value of €2.7 Billion Intralot S.A. (ATSE: INLOT) (“Intralot”) and Bally’s Corporation (NYSE: BALY) (“Bally’s”) today announced that their respective Boards of Directors approved their entry into a definitive transaction agreement (“Transaction Agreement”) pursuant to which Intralot will acquire Bally’s International Interactive business (the “International Interactive Business”) in a cash-and-shares transaction that values the International Interactive Business at an enterprise value of €2.7 billion (the “Transaction”). The consideration for the acquisition of the International Interactive Business will comprise a combination of cash paid by Intralot and newly issued shares delivered by Intralot to Bally’s, as more specifically detailed below. As part of the Transaction, Intralot expects to refinance part of its existing debt facilities and Bally’s also expects to repay secured debt from the cash proceed
Valeo Foods Group Acquires Melegatti Cakes Expanding the Italian Bakery Portfolio1.7.2025 18:21:00 CEST | Press release
Valeo Foods Group, one of Europe’s leading producers of quality sweets, treats and snacks, has successfully acquired the assets of an Italian panettone, pandoro and croissant producer, Melegatti 1894 S.p.A.This acquisition is another step forward in Valeo Foods Groups’ strategy to expand its baked sweet treats portfolio, and reinforces Valeo’s commitment to bringing authentic Italian confections and established regional brands to a wider international audience. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250702677156/en/ Melegatti Founded in 1894 in Verona, Melegatti has a strong reputation for artisanal cakes - particularly pandoro, panettone and filled croissants - traditional recipes, and a rich Italian heritage, Melegatti has a proud legacy founded on family values, craftsmanship, and a passion for quality. “We are excited to welcome Melegatti into the Valeo Foods Group,” said Ronald Kers, Group CEO. “This acquisition
PUMA and Borussia Dortmund Extend Partnership1.7.2025 18:18:00 CEST | Press release
Sports company PUMA has extended its long-standing partnership with Borussia Dortmund, and will continue to create products that cater to BVB’s many passionate fans around the world and match the club’s dynamic, fast paced style of football. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250701775493/en/ Sports company PUMA has extended its long-standing partnership with Borussia Dortmund, and will continue to create products that cater to BVB’s many passionate fans around the world and match the club’s dynamic, fast paced style of football. Since the start of their partnership in the 2012/13 season, BVB has celebrated many successes, such as reaching the finals of the 2012/13 and 2023/24 UEFA Champions League and winning the 2016/17 and 2020/21 German DFB Cup. The club is currently participating in the FIFA Club World Cup, where it has already reached the round of 16. BVB continues to set the standard in European football w
Gogo Galileo HDX Coming to Cessna Citation Jet Models1.7.2025 17:00:00 CEST | Press release
Expected FAA Supplemental Type Certification in late 2025 Textron Aviation Inc., a Textron Inc. (NYSE: TXT) company, today announced Gogo Galileo HDX will be available for aftermarket installation on Cessna Citation jets after Federal Aviation Administration (FAA) Supplemental Type Certification (STC) expected in late 2025. The global Low Earth Orbit (LEO) solution allows customers to enjoy one of the best possible in-flight connectivity and aviation experiences, no matter where their journey takes them. This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20250701750049/en/ Textron Aviation Inc., a Textron Inc. (NYSE: TXT) company, today announced Gogo Galileo HDX will be available for aftermarket installation on Cessna Citation jets after Federal Aviation Administration (FAA) Supplemental Type Certification (STC) expected in late 2025. (Photo: Textron Aviation) By offering Gogo Galileo HDX as an aftermarket upgrade, the Textron Av
In our pressroom you can read all our latest releases, find our press contacts, images, documents and other relevant information about us.
Visit our pressroom