REG - AstraZeneca PLC - Enhertu granted Priority Review for breast cancer

AstraZenecaAnnouncement

17/01/2022 07:05

For best results when printing this announcement, please click on link below:
http://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20220117:nRSQ5614Ya&default-theme=true

RNS Number : 5614Y  AstraZeneca PLC  17 January 2022

 

17 January 2022 07:00 GMT

 

Enhertu granted Priority Review in the US for patients with HER2-positive
metastatic breast cancer treated with a prior anti-HER2-based regimen

 

Based on ground-breaking DESTINY-Breast03 results showing AstraZeneca and
Daiichi Sankyo's Enhertu reduced the risk of disease progression or death by
72% versus trastuzumab emtansine (T-DM1)

 

Application being evaluated under FDA Real-Time Oncology Review and Project
Orbis

 

AstraZeneca and Daiichi Sankyo have received notification of acceptance of the
supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab
deruxtecan) for the treatment of adult patients in the US with unresectable or
metastatic HER2-positive breast cancer who have received a prior
anti-HER2-based regimen. The application has also been granted Priority
Review.

 

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

 

The Food and Drug Administration (FDA) grants Priority Review to applications
for medicines that, if approved, would offer significant improvements over
available options by demonstrating safety or efficacy improvements, preventing
serious conditions, or enhancing patient compliance.(1) The Prescription Drug
User Fee Act (PDUFA) date, the FDA action date for their regulatory decision,
is during the second quarter of 2022.

 

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR)
programme and Project Orbis, two initiatives of the FDA which are designed to
bring effective cancer treatments to patients as early as possible. RTOR
allows the FDA to review components of an application before submission of the
complete application. Project Orbis provides a framework for concurrent
submission and review of oncology medicines among participating international
partners.

 

Breast cancer is the most common cancer worldwide, with more than two million
cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.(2)
Approximately one in five cases of breast cancer are considered
HER2-positive.(3) Despite initial treatment with trastuzumab and a taxane,
patients with HER2-positive metastatic breast cancer will often experience
disease progression.(4) More treatment options are needed to further delay
progression and extend survival.(4-6)

 

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said:
"This review across geographies and the Priority Review in the US as part of
Project Orbis is so important because it speaks to the transformative
potential of Enhertu based on the unprecedented progression-free survival
benefit in this setting. The news reinforces the importance of bringing this
potential new option to patients as quickly as possible."

 

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This regulatory
review of Enhertu in the US marks the first time this medicine is
participating in both the Real-Time Oncology Review and Project Orbis
programmes. The FDA's prioritisation of our application underscores the
potential of this medicine and the continued need to expedite the availability
of new treatment options, while making it possible to potentially receive
approvals in several countries concurrently."

 

The sBLA is based on data from the DESTINY-Breast03 trial presented
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/enhertu-reduced-the-risk-of-disease-progression-or-death-by-72-vs-trastuzumab-emtansine-t-dm1-in-patients-with-her2-positive-metastatic-breast-cancer.html)
during the European Society for Medical Oncology (ESMO) Congress 2021.

 

In the trial, Enhertu demonstrated a 72% reduction in the risk of disease
progression or death compared to T-DM1 (hazard ratio  HR  0.28; 95% confidence
interval  CI : 0.22-0.37; p=7.8x10(-22)) in patients with HER2-positive
unresectable and/or metastatic breast cancer previously treated with
trastuzumab and a taxane.

 

DESTINY-Breast03 also recorded that nearly all patients treated with Enhertu
during the trial were alive at one year (94.1%) compared to 85.9% of patients
treated with T-DM1. Confirmed objective response rate (ORR) more than doubled
in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%). The safety profile
of Enhertu was consistent with previous clinical trials, with no new safety
concerns identified and no Grade 4 or 5 treatment-related interstitial lung
disease events.

 

In September 2021, Enhertu received its fourth Breakthrough Therapy
Designation
(https://www.astrazeneca.com/media-centre/press-releases/2021/enhertu-granted-btd-for-breast-cancer.html)
(BTD) in the US 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 approved 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 in more than 30 countries based on the results from
the DESTINY-Breast01 trial.

 

Enhertu is being further assessed in a comprehensive clinical development
programme evaluating efficacy and safety across multiple HER2-targetable
cancers, including breast, gastric, lung and colorectal cancers.

 

Notes

 

HER2-positive breast cancer

Breast cancer is the most common cancer and is one of the leading causes of
cancer-related deaths in women worldwide.(2) More than two million patients
with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths
globally.(2) Approximately one in five cases of breast cancer are considered
HER2-positive.(3)

 

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.(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 and a taxane, people with
HER2-positive metastatic breast cancer will often experience disease
progression.(4) More treatment options are needed to further delay progression
and extend survival.(4-6)

 

DESTINY-Breast03

DESTINY-Breast03 is a global head-to-head, randomised, open-label,
registrational Phase III trial evaluating the safety and efficacy of Enhertu
(5.4mg/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 progression-free survival
(PFS) based on blinded independent central review. Secondary efficacy
endpoints include overall survival, ORR, duration of response, PFS based on
investigator assessment and safety.

 

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in
Asia, Europe, North America, Oceania and South America. For more information
about the trial, visit ClinicalTrials.gov
(https://clinicaltrials.gov/ct2/show/NCT03529110) .

 

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 30 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. A Type II Variation is currently under review
by the European Medicines Agency (EMA) 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 based on the results from the
DESTINY-Breast03 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
gastroesophageal junction adenocarcinoma who have received a prior
trastuzumab-based regimen based on the results from the DESTINY-Gastric01
trial. A Type II Variation is currently under review by the EMA for the
treatment of adult patients with locally advanced or metastatic HER2-positive
gastric or gastroesophageal junction adenocarcinoma who have received a prior
anti-HER2-based regimen.

 

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.

 

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of
two significant advancements in the "ASCO Clinical Advance of the Year:
Molecular Profiling Driving Progress in GI Cancers," based on data from both
the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted
therapy advances of the year in non-small cell lung cancer (NSCLC), based on
the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

 

Daiichi Sankyo collaboration

Daiichi Sankyo Company, Limited (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, and datopotamab
deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where
Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for
manufacturing and supply of Enhertu and datopotamab deruxtecan.

 

AstraZeneca in breast cancer

Driven by a growing understanding of breast cancer biology, AstraZeneca is
starting to challenge, and redefine, the current clinical paradigm for how
breast cancer is classified and treated to deliver even more effective
treatments to patients in need - with the bold ambition to one day eliminate
breast cancer as a cause of death.

 

AstraZeneca has a comprehensive portfolio of approved and promising compounds
in development that leverage different mechanisms of action to address the
biologically diverse breast cancer tumour environment. AstraZeneca aims to
continue to transform outcomes for HR-positive breast cancer with foundational
medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the
next-generation oral selective oestrogen receptor degrader (SERD) and
potential new medicine camizestrant.

 

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for
metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca
with MSD (Merck & Co., Inc. in the US and Canada) continue to research
Lynparza in metastatic breast cancer patients with an inherited BRCA mutation
and are exploring new opportunities to treat these patients earlier in their
disease.

 

Building on the first approval of Enhertu, a HER2-directed ADC, in previously
treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo
are exploring its potential in earlier lines of treatment and in new breast
cancer settings.

 

To bring much needed treatment options to patients with triple-negative breast
cancer, an aggressive form of breast cancer, AstraZeneca is testing
immunotherapy Imfinzi (durvalumab) in combination with other oncology
medicines, including Lynparza and Enhertu, evaluating the potential of AKT
kinase inhibitor, capivasertib, in combination with chemotherapy, and
collaborating with Daiichi Sankyo to explore the potential of TROP2-directed
ADC, datopotamab deruxtecan.

 

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. FDA. Priority Review. Available at:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review.
Accessed January 2022.

2. 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; 10.3322/caac.21660.

3. Ahn S, et al. HER2 status in breast cancer: changes in guidelines and
complicating factors for interpretation. J Pathol Transl Med. 2020; 54(1):
34-44.

4. Barok M, et al. Trastuzumab emtansine: mechanism of action and drug
resistance. Breast Cancer Res. 2014; 16(2):209.

5. Mounsey L, et al. Changing Natural History of HER2-Positive Breast Cancer
Metastatic to the Brain in the Era of New Targeted Therapies. Clin Breast
Cancer. 2018; 18(1):29-37.

6. Martinez-S Sáez O, et al. Current and Future Management of HER2-Positive
Metastatic Breast Cancer. JCO Oncol Pract. 2021. 10.1200/OP.21.00172.

7. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers:
Overexpression and Therapeutic Implications. Mol Biol Int. 2014;852748.

8. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the
Lung Cancer Mutation Consortium. Cancer. 2017;1;123(21):4099-4105.

 

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  MSCFFFLFLVIRLIF