- Submission based on DESTINY-Breast06 phase 3 trial results that
showed Daiichi Sankyo and AstraZeneca’s ENHERTU demonstrated a
statistically significant and clinically meaningful improvement in
progression-free survival compared to standard of care
chemotherapy
Daiichi Sankyo (TSE: 4568) today announced that the European
Medicines Agency (EMA) has validated the Type II Variation
application for ENHERTU® (trastuzumab deruxtecan) as a monotherapy
for the treatment of adult patients with unresectable or metastatic
HER2 low (defined as IHC 1+ or IHC 2+/ISH-) or HER2 ultralow
(defined as IHC 0 with membrane staining) breast cancer who have
received at least one endocrine therapy in the metastatic
setting.
ENHERTU is a specifically engineered HER2 directed DXd antibody
drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly
developed and commercialized by Daiichi Sankyo and AstraZeneca
(LSE/STO/Nasdaq: AZN).
Validation confirms that the application is complete and
commences the scientific review process by the EMA’s Committee for
Medicinal Products for Human Use. This application is based on data
from the DESTINY-Breast06 phase 3 trial presented as a
late-breaking oral session at the 2024 American Society of Clinical
Oncology (#ASCO24) Annual Meeting.
“This submission builds on our existing indication for ENHERTU
in patients with HER2 low metastatic breast cancer and an expanded
approval would enable the potential for use in an earlier disease
setting as well as in a broader patient population that now
includes HER2 ultralow,” said Ken Takeshita, MD, Global Head,
R&D, Daiichi Sankyo. “We look forward to working closely with
the EMA to potentially bring this medicine to more patients in the
EU.”
Additional regulatory submissions for ENHERTU in this indication
are underway globally.
About DESTINY-Breast06
DESTINY-Breast06 is a global, randomized, open-label, phase 3
trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg)
versus investigator’s choice of chemotherapy (capecitabine,
paclitaxel or nab paclitaxel) 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 no prior chemotherapy for advanced or
metastatic disease and received at least two lines of prior
endocrine therapy in the metastatic setting. Patients also were
eligible if they had received one prior line of endocrine therapy
combined with a CDK4/6 inhibitor in the metastatic setting and
experienced disease progression within six months of starting
first-line treatment or received endocrine therapy as an adjuvant
treatment and experienced disease recurrence within 24 months.
The primary endpoint is progression-free survival (PFS) in the
HR positive, HER2 low patient population as measured by blinded
independent central review (BICR). Key secondary endpoints include
PFS by BICR in the overall trial population (HER2 low and HER2
ultralow), overall survival (OS) in patients in the HER2 low
patient population and OS in the overall trial population. Other
secondary endpoints include objective response rate, duration of
response, time to first subsequent treatment or death, time to
second subsequent treatment or death and safety. Analysis of the
HER2 ultralow subgroup was not powered to demonstrate statistical
significance.
DESTINY-Breast06 enrolled 866 patients (n=713 for HER2 low and
n=153 for HER2 ultralow) at multiple sites in Asia, Europe, North
America, Oceania and South America. For more information about the
trial, visit ClinicalTrials.gov.
About Breast Cancer and HER2 Expression
Breast cancer is the second most common cancer and one of the
leading causes of cancer-related deaths worldwide.1 More than two
million breast cancer cases were diagnosed in 2022 with more than
665,000 deaths globally.1 In Europe, approximately 557,000 cases of
breast cancer are diagnosed annually.2 While survival rates are
high for those diagnosed with early breast cancer, only about 30%
of patients diagnosed with 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 of tumors, including breast
cancer.4 Patients with high levels of HER2 expression (IHC 3+ or
IHC2+/ISH+) are classified 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 classified as HER2 negative, despite the fact
that many of these tumors still carry some level of HER2
expression.6 It is estimated that approximately 60% to 65% of HR
positive, HER2 negative breast cancers are HER2 low and potentially
an additional 25% may be HER2 ultralow.7,8
Endocrine therapies are widely given consecutively in the early
lines of treatment for HR positive metastatic breast cancer.9
However, following two lines of endocrine therapy, further efficacy
with additional endocrine treatment is often limited.9 The current
standard of care following endocrine therapy is chemotherapy, which
is 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 on the DESTINY-Breast04 trial,
there were no targeted therapies approved specifically for patients
with HER2 low expression.13 There are no targeted therapies
specifically approved for patients with HER2 ultralow
expression.14
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 number of topoisomerase
I inhibitor 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 patients with unresectable or
metastatic HER2 positive (IHC 3+ or in-situ hybridization (ISH)+)
breast cancer who have received a 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 (5.4 mg/kg) is approved in more than 65 countries
worldwide for the treatment of adult patients with unresectable or
metastatic HER2 low (IHC 1+ or IHC 2+/ISH-) 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.
ENHERTU (5.4 mg/kg) is approved in more than 35 countries
worldwide for the treatment of adult patients with unresectable or
metastatic NSCLC whose tumors have activating HER2 (ERBB2)
mutations, as detected by a locally or regionally approved test,
and who have received a prior systemic therapy based on the results
from the DESTINY-Lung02 trial. Continued approval in the U.S. for
this indication may be contingent upon verification 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 patients with 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 results from the
DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06
trials. Full approval in China for this indication will depend on
whether a randomized controlled confirmatory clinical trial can
demonstrate clinical benefit in this population.
ENHERTU (5.4 mg/kg) is approved in the U.S. for the treatment of
adult patients with unresectable or metastatic HER2 positive (IHC
3+) solid tumors who have received prior systemic treatment and
have no satisfactory 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 be contingent 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 of ENHERTU monotherapy across
multiple HER2 targetable cancers. Trials in combination with other
anticancer 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 commercialize ENHERTU in March
2019 and datopotamab deruxtecan 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 ENHERTU
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 across multiple types of cancer.
ENHERTU, a HER2 directed ADC, and datopotamab deruxtecan
(Dato-DXd), a TROP2 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-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6
directed ADC, are being jointly developed and commercialized
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 cytotoxic payload inside cancer cells that
express a specific cell surface antigen, 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.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab
deruxtecan, raludotatug deruxtecan and DS-3939 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.
_________________________ References 1 Bray F, et al. CA
Cancer J Clin. 2024; 10.3322/caac.21834. 2 Globocan 2022. Breast
Cancer. Accessed August 2024. 3 National Cancer Institute. SEER
Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed August
2024. 4 Iqbal N, et al. Mol Biol Int. 2014;852748. 5 Ahn S, et al.
J Pathol Transl Med. 2020;54(1):34-44. 6 Sajjadi E, et al. Cancer
Drug Resist. 2022;5(4):882-888. 7 Denkert C, et al. Lancet Oncol.
2021 Aug;22(8):1151-1161. 8 Chen Z, et al. Breast Cancer Res Treat.
2023 Nov;202(2):313-323. 9 Manohar P, et al. Cancer Biol Med. 2022
Feb 15; 19(2):202–212. 10 Cortes J, et al. Lancet.
2011;377:914-923. 11 Yuan P, et al. Eur J Cancer. 2019;112:57-65.
12 Jerusalem G, et al. JAMA Oncol. 2018;4(10):1367–1374. 13 Modi S,
et al. N Engl J Med. 2022;387:9-20. 14 Eiger D, et al. Cancers.
2021 Mar; 13(5): 1015.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240818615324/en/
Media:
Global/US: Jennifer Brennan Daiichi Sankyo, Inc.
jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile)
EU: Simone Jendsch-Dowé Daiichi Sankyo Europe GmbH
simone.dowe@daiichi-sankyo.eu +49 (89) 78080 (office)
Japan: Daiichi Sankyo Co., Ltd.
DS-PR@daiichisankyo.co.jp
Investor Relations:
DaiichiSankyoIR@daiichisankyo.co.jp