REG - AstraZeneca PLC - Enhertu approved in EU for gastric cancer

AstraZenecaAnnouncement

19/12/2022 07:15

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20221219:nRSS0762Ka&default-theme=true

RNS Number : 0762K  AstraZeneca PLC  19 December 2022

19 December 2022 07:15 GMT

 

Enhertu approved in the EU for patients with previously treated HER2-positive
advanced gastric cancer

 

First HER2-directed medicine to be approved for gastric cancer in the EU

in more than a decade

 

Based on DESTINY-Gastric02 and DESTINY-Gastric01 where AstraZeneca and

Daiichi Sankyo's Enhertu demonstrated clinically meaningful efficacy

 

AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has been
approved in the European Union (EU) as monotherapy for the treatment of adult
patients with advanced HER2-positive gastric or gastroesophageal junction
(GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

 

Enhertu is a specifically engineered HER2-directed antibody drug conjugate
(ADC) being jointly developed and commercialised by AstraZeneca and Daiichi
Sankyo.

 

The approval by the European Commission follows the positive opinion
(https://www.astrazeneca.com/media-centre/press-releases/2022/enhertu-recommended-for-approval-in-the-eu-by-chmp-for-patients-with-previously-treated-her2-positive-advanced-gastric-cancer.html)
of the Committee for Medicinal Products for Human Use in November 2022 and is
based on results from the DESTINY-Gastric02 and DESTINY-Gastric01 Phase II
trials.

 

In DESTINY-Gastric02, which enrolled patients from North America and Europe,
treatment with Enhertu resulted in a confirmed objective response rate (ORR)
of 41.8% as assessed by independent central review (ICR). Median duration of
response (DoR) was 8.1 months.

 

In DESTINY-Gastric01, which enrolled patients from Japan and South Korea,
treatment with Enhertu resulted in a confirmed ORR of 40.5% versus 11.3% with
chemotherapy (irinotecan or paclitaxel) as 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% reduction in the risk of death versus patients treated
with chemotherapy (based on a hazard ratio of 0.59; 95% confidence interval:
0.39-0.88; p=0.0097) with a median overall survival (OS) of 12.5 months versus
8.4 months.

 

Approximately 136,000 cases of gastric cancer are diagnosed annually in
Europe, where it represents the sixth leading cause of cancer death.(1,2)
Gastric cancer is typically diagnosed in the advanced stage. Even when the
disease is diagnosed at earlier stages, the survival rate remains modest.(3,4)
Approximately one in five gastric cancers are HER2-positive.(5,6)

 

Eric Van Cutsem, MD, PhD, Head of Department of Oncology at the University of
Leuven, Belgium and Founding Chair of the ESMO-GI/World Congress of
Gastrointestinal Cancers, said: "Today's news is a welcome advance for
patients with HER2-positive advanced gastric cancer. Patients with this
disease face poor outcomes following progression on initial treatment with a
HER2-directed medicine as many do not respond to further treatment, and even
those that do respond often do not have durable responses. Data from the
DESTINY-Gastric02 and DESTINY-Gastric01 trials support Enhertu becoming a new
standard of care for patients in this setting."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "Today's important approval makes Enhertu the first
HER2-directed medicine to be approved for gastric cancer in the European Union
in more than a decade. Patients across the EU with advanced HER2-positive
disease who have progressed following treatment in the first-line setting, may
now have the opportunity to benefit from treatment with Enhertu."

 

Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi
Sankyo, Inc., said: "Enhertu is the first antibody drug conjugate to be
approved in Europe for advanced gastric cancer, representing a major advance
in treating this difficult-to-treat cancer. With this approval, we can now
offer patients with previously treated HER2-positive gastric cancer a
treatment with clinically meaningful efficacy."

 

In both trials, the safety profiles observed in patients treated with Enhertu
were consistent with those seen in other trials of Enhertu with no new safety
signals identified.

 

Enhertu is also approved in the US and several other countries for locally
advanced or metastatic HER2-positive gastric cancer.

 

Notes

 

Financial considerations

Following EU approval, an amount of $35m is due from AstraZeneca to Daiichi
Sankyo as a milestone payment for the previously treated HER2-positive gastric
indication. The milestone payment will be capitalised as an addition to the
upfront payment made by AstraZeneca to Daiichi Sankyo in 2019 and subsequent
capitalised milestones.

 

Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo.
AstraZeneca reports its share of gross profit margin from Enhertu sales in
those territories as collaboration revenue in the Company's financial
statements. AstraZeneca will record product sales in respect of sales made in
territories where AstraZeneca is the selling party.

 

Further details on the financial arrangements were set out in the March 2019
announcement
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html)
of the collaboration.

 

HER2-positive gastric cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the
fourth highest leading cause of cancer mortality, with a five-year global
survival rate of 5% to 10% for advanced or metastatic disease.(3,7,8)
Approximately one million new patients were diagnosed with gastric cancer in
2020, with 768,000 deaths reported globally.(2) In Europe, approximately
136,000 cases of gastric cancer are diagnosed annually, and Eastern Europe has
the second highest incidence of gastric cancer worldwide after Eastern
Asia.(2,8) Gastric cancer is the sixth leading cause of cancer death in Europe
and is typically diagnosed in the advanced stage. Even when diagnosed in
earlier stages of the disease, the survival rate remains modest.(1,3,4)

 

Approximately one in five gastric cancers are HER2-positive.(5,6) HER2 is a
tyrosine kinase receptor growth promoting protein expressed on the surface of
many types of tumours including breast, gastric, lung and colorectal
cancers.(5) HER2 overexpression may be associated with a specific HER2 gene
alteration known as HER2 amplification.(6)

 

Recommended first-line treatment in the EU for HER2-positive advanced or
metastatic gastric cancer is combination chemotherapy plus trastuzumab, an
anti-HER2 medicine, which has been shown to improve survival outcomes when
added to chemotherapy.(9,10) For patients with metastatic gastric cancer that
progresses following initial treatment with a trastuzumab-based regimen, there
were previously no other approved HER2-directed medicines in the EU prior to
the approval of Enhertu.(7,11,12)

 

DESTINY-Gastric02

DESTINY-Gastric02 is an open-label, single-arm Phase II trial in patients
evaluating the efficacy and safety of Enhertu (6.4mg/kg) in patients with
HER2-positive metastatic and/or unresectable gastric or GEJ adenocarcinoma
with disease progression on or after a trastuzumab-containing regimen.

 

The primary endpoint of DESTINY-Gastric02 is confirmed ORR based on ICR.
Secondary endpoints include progression-free survival (PFS), OS, DoR and
safety.

 

DESTINY-Gastric02 enrolled 79 patients at multiple sites in North America and
Europe. For more information about the trial, visit ClinicalTrials.gov
(https://clinicaltrials.gov/ct2/show/NCT04014075) .

 

DESTINY-Gastric01

DESTINY-Gastric01 is a randomised, open-label Phase II trial evaluating the
efficacy and safety of Enhertu (6.4mg/kg) in patients with primarily
HER2-positive (defined as immunohistochemistry  IHC  3+ or IHC 2+/in-situ
hybridisation  ISH +) advanced gastric cancer or GEJ adenocarcinoma with
disease progression following two or more prior treatment regimens including
fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were
randomised 2:1 to receive Enhertu or physician's choice of chemotherapy
(paclitaxel or irinotecan monotherapy).

 

The primary endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints include
OS, PFS, DoR, disease control rate and time to treatment failure, as well as
pharmacokinetic and safety endpoints.

 

DESTINY-Gastric01 enrolled 187 patients at multiple sites in Japan and South
Korea. For more information about the trial, visit ClinicalTrials.gov
(https://clinicaltrials.gov/ct2/show/NCT03329690) .

 

Enhertu

Enhertu 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 programme 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 (5.4mg/kg) is approved in more than 40 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 (5.4mg/kg) 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 (5.4mg/kg) is approved in Brazil and the US 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 chemotherapy 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 (5.4mg/kg) is approved under accelerated approval in the US for the
treatment of adult patients with unresectable or metastatic non-small cell
lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected
by an FDA-approved test, and who have received a prior systemic therapy, based
on the results of the DESTINY-Lung02 trial. Continued approval for this
indication may be contingent upon verification and description of clinical
benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of
adult patients with locally advanced or metastatic HER2-positive gastric or
GEJ who have received a prior trastuzumab-based regimen based on the results
from the DESTINY-Gastric01 and/or DESTINY-Gastric02 trial.

Enhertu development programme

A comprehensive development programme is underway globally, 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 in breast, non-small cell lung and gastric
cancer are currently under review in several countries.

 

Daiichi Sankyo collaboration

Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo]
and AstraZeneca entered into a global collaboration to jointly develop and
commercialise Enhertu (a HER2-directed ADC) in March 2019
(https://www.astrazeneca.com/media-centre/press-releases/2019/astrazeneca-and-daiichi-sankyo-enter-collaboration-for-novel-her-2-targeting-antibody-drug-conjugate.html#modal-historic-confirmation)
, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020
(https://www.astrazeneca.com/media-centre/press-releases/2020/astrazeneca-and-daiichi-sankyo-enter-collaboration-to-develop-and-commercialise-new-antibody-drug-conjugate.html#modal-historic-confirmation)
, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi
Sankyo is responsible for the manufacturing and supply of Enhertu and
datopotamab deruxtecan.

 

AstraZeneca in gastrointestinal cancers

AstraZeneca has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines and a variety of tumour
types and stages of disease. In 2020, GI cancers collectively represented
approximately 5.1 million new cancer cases leading to approximately 3.6
million deaths.(13)

 

Within this programme, the Company is committed to improving outcomes in
gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.

 

Imfinzi (durvalumab) is approved in the US in combination with chemotherapy
(gemcitabine plus cisplatin) for advanced biliary tract cancer and in
combination with Imjudo in unresectable hepatocellular carcinoma. Imfinzi is
being assessed in combinations, including with Imjudo in liver,
oesophageal and gastric cancers in an extensive development programme
spanning early to late-stage disease across settings.

 

Enhertu, a HER2-directed antibody drug conjugate, is approved in HER2-positive
advanced gastric cancer and is being assessed in colorectal
cancer. Enhertu is jointly developed and commercialised by AstraZeneca and
Daiichi Sankyo.

 

Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in
BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and
commercialised in collaboration with MSD (Merck & Co., Inc. inside the US
and Canada).

 

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand cancer and
all its complexities to discover, develop and deliver life-changing medicines
to patients.

 

The Company's focus is on some of the most challenging cancers. It is through
persistent innovation that AstraZeneca has built one of the most diverse
portfolios and pipelines in the industry, with the potential to catalyse
changes in the practice of medicine and transform the patient experience.

 

AstraZeneca has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.

 

AstraZeneca

AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical
company that focuses on the discovery, development, and commercialisation of
prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals,
including Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   WHO. Cancer Today Europe Mortality. Available at:
https://gco.iarc.fr/today/online-analysis-table.
(https://gco.iarc.fr/today/online-analysis-table.%20Accessed%20December%202022)
Accessed December 2022.

2.   WHO. International Agency of Cancer Research. Cancer Today. Stomach
Incidence. 2020. Available at:
https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf
(https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf) .
Accessed December 2022.

3.   SEER Cancer Stat Facts: Stomach Cancer. Available at:
https://seer.cancer.gov/statfacts/html/stomach.html
(https://seer.cancer.gov/statfacts/html/stomach.html.%20Accessed%20November%202022)
. Accessed December 2022.

4.   Cancer Research UK. Stomach Cancer Survival Statistics. Available at:
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero
(https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/stomach-cancer/survival#heading-Zero)
. Accessed December 2022.

5.   Iqbal N, et al. Human epidermal growth factor receptor 2 (HER2) in
cancers: overexpression and therapeutic implications. Mol Biol Int. 2014;
2014:852748.

6.   Abrahao-Machado LF, et al. HER2 testing in gastric cancer: an update.
World J Gastroenterol. 2016; 22(19):4619-4625.

7.   Casamayor M, et al. Targeted literature review of the global burden of
gastric cancer. Ecancermedicalscience. 2018; 12:883.

8.   Sung. H et al. Global cancer statistics 2020: GLOBOCAN estimates of
incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J
Clin. 2021; 71(3):209-249.

9.   Orditura M, et al. Treatment of gastric cancer. World J Gastroenterol.
2014; 20(7):1635-1649.

10.  Lordick F, et al. Gastric cancer: ESMO Clinical Practice Guideline for
diagnosis, treatment and follow-up. Ann Oncol. 2022 Oct;33(10):1005-1020.

11.  Thuss-Patience PC, et al. Trastuzumab emtansine versus taxane use for
previously treated HER2-positive locally advanced or metastatic gastric or
gastro-oesophageal junction adenocarcinoma (GATSBY): an international
randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017;
18(5):640-653.

12.  Satoh T, et al. Lapatinib plus paclitaxel versus paclitaxel alone in the
second-line treatment of HER2-amplified advanced gastric cancer in asian
populations: TyTAN-a randomized, phase III study. J Clin Oncol. 2014;
32(19):2039‐2049.

13.  WHO. World Cancer Fact Sheet. Available at:
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
(https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf)
. Accessed December 2022.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCBRBDDUXBDGDI