a9827l
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of January 2021
Commission
File Number: 001-11960
AstraZeneca PLC
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Enhertu approved in the US for gastric
cancer
18 January 2021 07:00 GMT
Enhertu approved in the US for the treatment of
patients with
previously treated HER2-positive advanced gastric
cancer
First HER2-directed medicine approved for patients with gastric
cancer in a decade
AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi
Sankyo)'s Enhertu (trastuzumab
deruxtecan) has been approved in the US 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.
In the US, gastric cancer is most frequently diagnosed in
the advanced stage, with only approximately 5% of patients
surviving beyond five years.1,2 Approximately
one in five gastric cancers are HER2 positive.3
The approval by the Food and Drug Administration (FDA) was based on
the positive results from the randomised DESTINY-Gastric01 Phase II
trial conducted in Japan and South Korea. In the
trial, Enhertu demonstrated a statistically
significant and clinically meaningful improvement in overall
survival (OS) and objective response rate (ORR) versus
chemotherapy (irinotecan or paclitaxel) in patients with
advanced gastric cancer or GEJ adenocarcinoma who had progressed on
at least two or more prior regimens including trastuzumab plus a
fluoropyrimidine- and platinum-based chemotherapy
combination.4
Ronan Kelly, MD, MBA, Director of the Charles A. Sammons Cancer
Center and the W.W. Caruth, Jr. Chair of Immunology at Baylor
University Medical Center, Dallas, Texas, US, said: "Patients with
metastatic HER2-positive gastric cancer with progression following
1st-line treatment have historically faced poor outcomes, including
low response to treatment and rapid disease progression. This
approval represents the first time a HER2-directed medicine has
demonstrated a significant improvement in survival compared to
chemotherapy following initial treatment in the metastatic setting,
and it has the potential to become the new standard of care for
this patient population."
Dave Fredrickson, Executive Vice President, Oncology Business Unit,
said: "Today's approval of Enhertu represents the first HER2-directed medicine
approved in a decade for patients with HER2-positive metastatic
gastric cancer. The results from the DESTINY-Gastric01 trial
highlight the potential to change clinical practice, showing a 41
per cent improvement in survival and a response rate more than
three times higher with Enhertu compared to chemotherapy. We are thrilled to
bring this important medicine to more patients and physicians in
the US."
Antoine Yver, Executive Vice President and Global Head, Oncology
Research and Development, Daiichi Sankyo, said:
"Enhertu is
the first antibody drug conjugate to receive approval in the US for
the treatment of patients with metastatic gastric cancer, and
represents a major advance in managing this difficult-to-treat
disease. This second indication in the US represents an important
step forward in our ambitious plan to accelerate the development
of Enhertu across a broad range of HER2-targetable
cancers."
In a pre-specified interim analysis from the DESTINY-Gastric01
trial, patients treated with Enhertu had a 41% reduction in the risk of death
versus patients treated with chemotherapy (based on a hazard ratio
[HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097)
with a median OS of 12.5 months versus 8.4
months.3
Confirmed ORR, assessed by independent central review was a major
efficacy outcome. Results showed a confirmed ORR
of 40.5% in patients treated
with Enhertu (n=126) compared
to 11.3% in patients treated with chemotherapy (n=62). Patients
treated with Enhertu had a 7.9% complete response rate and a
32.5% partial response rate compared to a complete response rate of
0% and a partial
response rate of 11.3% for
patients treated with chemotherapy.4
Enhertu demonstrated
a median
progression-free survival (PFS) of 5.6 months compared to 3.5
months with chemotherapy (HR=0.47; 95% CI 0.31-0.71).
Additionally, Enhertu showed a median duration of
response (DoR) of 11.3 months versus 3.9 months with
chemotherapy.4
Results from the DESTINY-Gastric01 trial were published
in The
New England Journal of Medicine in
June 2020.5
The most common adverse reactions, including laboratory
abnormalities, of any grade (greater than or equal to 20%) for
patients treated with Enhertu (n=125) in the DESTINY-Gastric01 trial were
anaemia, leukopenia, neutropenia, lymphocytopenia,
thrombocytopenia, nausea, decreased appetite, increased aspartate
aminotransferase, fatigue, increased blood alkaline phosphatase,
increased alanine aminotransferase, diarrhoea, hypokalaemia,
vomiting, constipation, increased blood bilirubin, pyrexia and
alopecia. Interstitial lung disease or pneumonitis occurred in 10%
of patients.4
This is the second indication approved for Enhertu in the US following the accelerated approval
for adult patients with unresectable or metastatic HER2-positive
breast cancer who have received two or more prior anti-HER2-based
regimens in the metastatic setting based on the DESTINY-Breast01
trial.
Enhertu was previously
granted Priority
Review, Breakthrough
Therapy Designation (BTD)
in HER2-positive metastatic gastric cancer
and Orphan Drug
Designation for gastric
cancer by the FDA. Two additional Phase II trials,
DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further
evaluating treatment with Enhertu in patients with HER2-positive metastatic
gastric cancer.
Financial considerations
Following US approval, an amount of $115m is due from AstraZeneca
to Daiichi Sankyo as a combined 2nd-line and 3rd-line milestone
payment in HER2-positive gastric cancer. In AstraZeneca, the
milestones paid will be capitalised as an addition to the upfront
payment made in 2019 and subsequent capitalised milestones and
amortised through the profit and loss.
Sales of Enhertu in the US are recognised by Daiichi Sankyo.
AstraZeneca reports its share of gross profit margin
from Enhertu sales in the US as collaboration revenue in
the Company's financial statements. For further details on the
financial arrangements, please consult the collaboration agreement
from March 2019.
Gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide
and the third leading cause of cancer mortality with a five-year
survival rate of 5% for metastatic disease; there were
approximately one million new cases reported in 2020 and more than
768,000 deaths.6 In
the US, it is estimated that 27,600 new cases of gastric cancer
were diagnosed in 2020 and more than 11,000 people died from the
disease.7
Approximately one in five gastric cancers are HER2
positive.1 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. Gastric cancer is usually diagnosed in
the advanced stage, but even when diagnosed in earlier stages of
the disease the survival rate remains modest.2 Recommended
1st-line treatment 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. For patients with metastatic gastric cancer
that progresses following initial treatment with a
trastuzumab-based regimen, there were previously no other approved
HER2-targeted medicines prior to the approval
of Enhertu.8
DESTINY-Gastric01
DESTINY-Gastric01 is a Phase II, open-label, multi-centre,
randomised controlled trial testing the safety and efficacy
of Enhertu (6.4 mg/kg) versus investigator's choice of
chemotherapy in a primary cohort of patients from Japan and South
Korea with HER2-positive (defined as IHC3+ or IHC2+/ISH+), locally
advanced or metastatic gastric cancer or GEJ adenocarcinoma who
have progressed on at least two or more prior regimens including
trastuzumab plus a fluoropyrimidine- and platinum-based
chemotherapy combination. Patients (n=188) were randomised 2:1 to
receive Enhertu or physician's choice of chemotherapy
(paclitaxel or irinotecan monotherapy). Patients were treated
with Enhertu 6.4mg/kg once every three weeks or
chemotherapy.
The main efficacy outcome measures were ORR, assessed by
independent central review, and OS. Additional efficacy outcome
measures were PFS and DoR.4
Enhertu
Enhertu (trastuzumab
deruxtecan; fam-trastuzuab deruxtecan-nxki in the US) is a
HER2-directed antibody drug conjugate (ADC). It is the lead ADC in
the oncology portfolio of Daiichi Sankyo and the most advanced
programme in AstraZeneca's ADC scientific
platform.
ADCs are targeted cancer medicines that deliver cytotoxic
chemotherapy ('payload') to cancer cells via a linker attached to a
monoclonal antibody that binds to a specific target expressed on
cancer cells. Enhertu is comprised of a humanised anti-HER2 IgG1
monoclonal antibody with the same amino acid sequence as
trastuzumab attached to a topoisomerase I inhibitor payload, an
exatecan derivative, via a tetrapeptide-based cleavable
linker.
Enhertu (5.4mg/kg) is
approved in the US under accelerated approval, and in Japan under
the conditional early approval system, 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 the metastatic setting based on the
DESTINY-Breast01 trial. In addition to the
US, Enhertu (6.4mg/kg) is also approved in Japan for
patients with HER2-positive unresectable advanced or recurrent
gastric cancer that progressed after chemotherapy based on the
DESTINY-Gastric01 trial.
Development programme
A comprehensive development programme is underway globally, with
nine registrational trials evaluating the efficacy and safety
of Enhertu monotherapy across multiple HER2 cancers,
including breast, gastric and lung cancers. Trials in combination
with other anticancer treatments, such as immunotherapy, are also
underway.
In May 2020, Enhertu received a BTD for the treatment of patients
with metastatic non-small cell lung cancer whose tumours have a
HER2 mutation and with disease progression on or after
platinum-based therapy.
Daiichi Sankyo collaboration
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 (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 gastrointestinal cancers
AstraZeneca has a broad development programme for the treatment of
gastrointestinal (GI) cancers across several medicines spanning a
variety of tumour types and stages of disease. In 2020, GI cancers
collectively represented over five million new cancer cases leading
to more than 3.5 million deaths.6 Within
this programme, the Company is committed to improving outcomes in
gastric, liver, oesophageal, pancreatic, and colorectal
cancers.
The Company aims to understand the potential
of Enhertu in the two most common GI cancers,
colorectal and gastric cancers. Imfinzi (durvalumab) is being assessed as both as
monotherapy and in combinations including with tremelimumab across
the two main types of liver cancer, hepatocellular carcinoma and
biliary tract cancer, and in oesophageal and gastric
cancers. Lynparza (olaparib) is a first-in-class PARP
inhibitor with a broad and advanced clinical trial programme across
multiple GI tumour types including pancreatic and colorectal
cancers. Lynparza is developed and commercialised in
collaboration with MSD (Merck & Co., Inc. inside the US and
Canada).
AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly growing portfolio of new medicines that has the
potential to transform patients' lives and the Company's future.
With seven new medicines launched between 2014 and 2020,
and a broad pipeline of small molecules and biologics in
development, the Company is committed to advance oncology as a key
growth driver for AstraZeneca focused on lung, ovarian, breast and
blood cancers.
By harnessing the power of six scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage
Response, Antibody Drug Conjugates, Epigenetics, and Cell Therapies
- and by championing the development of personalised combinations,
AstraZeneca has the vision to redefine cancer treatment 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, primarily for the treatment of diseases in three therapy
areas - Oncology, 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 and
follow the Company on Twitter @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team, please
click here.
For Media contacts, click here.
References
1. Curea F.G, et al. Current
Targeted Therapies in HER2-Positive Gastric
Adenocarcinoma. Cancer Biotherapy &
Radiopharmaceuticals. 2017;32 (10).
2. American
Cancer Society. Stomach Cancer: Early Detection, Diagnosis, and
Staging. Available at: https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html.
3. American
Cancer Society. Stomach Cancer: Treating Stomach Cancer. Available
at: https://www.cancer.org/cancer/stomach-cancer/treating/targeted-therapies.html.
4. ENHERTU® [fam-trastuzumab
deruxtecan-nxki] US prescribing information;
2021.
5. Shitara, K et al. Trastuzumab
Deruxtecan in Previously Treated HER2-Positive Gastric
Cancer. N Engl J
Med. 2020;382(25):2419-2430. DOI:
10.1056/NEJMoa2004413.
6. Global Cancer
Observatory. Cancer Today. Lyon, France: International Agency for
Research on Cancer. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf .
7. American
Cancer Society. Stomach Cancer: About Stomach Cancer. Available
at: https://www.cancer.org/cancer/stomach-cancer/about/key-statistics.html.
8. NCCN
Guidelines® Gastric
Cancer. Version 4.2019. December 20, 2019:
MS-22-36.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
18 January 2021
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|