Blueprint
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 September
2018
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
FDA
approves AZ's Lumoxiti in hairy cell leukaemia
14
September 2018 07:00 BST
US FDA
approves Lumoxiti (moxetumomab
pasudotox-tdfk)
for certain patients with relapsed or refractory hairy cell
leukaemia
Approval of Lumoxiti, a first-in-class medicine for
hairy cell leukaemia
marks first new treatment option for patients in over 20
years1
75% of patients receiving Lumoxiti achieved
an
overall response; 30% had a durable complete
response2
AstraZeneca and MedImmune, its global biologics research and
development arm, announced today that the US Food and Drug
Administration (FDA) has approved Lumoxiti (moxetumomab pasudotox-tdfk) for the
treatment of adult patients with relapsed or refractory hairy cell
leukaemia (HCL) who have received at least two prior systemic
therapies, including treatment with a purine nucleoside
analog. Lumoxiti is not recommended in patients with severe
renal impairment (CrCl ≤ 29 mL/min).2 The
Phase III trial results demonstrated 75% (95% confidence interval
[CI]: 64, 84) of patients receiving Lumoxiti achieved an overall response; 30% (95% CI:
20, 41) had a durable complete response.2,3
Dave Fredrickson, Executive Vice-President, Global Head Oncology
Business Unit, said: "Today's FDA approval
of Lumoxiti represents a significant milestone for
people living with hairy cell leukaemia, a rare blood cancer that
can result in serious and life-threatening conditions. For
patients, this approval provides the first FDA-approved medicine
for this condition in more than 20 years."
Robert J. Kreitman, MD, Senior Investigator, Head of Clinical
Immunotherapy Section, Laboratory of Molecular Biology, Center for
Cancer Research, National Cancer Institute, and Principal
Investigator of the Phase III clinical trial, said: "While many
patients with hairy cell leukaemia experience a remission with
current treatments, 30% to 40% will relapse five to ten years after
their first treatment.4 With
subsequent treatments, durations of response diminish and
toxicities accumulate, and few approved treatment options
exist.5,6 Moxetumomab
pasudotox represents a promising non-chemotherapeutic agent for
HCL, addressing an unmet medical need for physicians and their
patients."
Lumoxiti was approved
under FDA Priority Review.7 The
approval is based on data from the Phase III single-arm, open-label
'1053' trial of Lumoxiti monotherapy in 80
patients who have received at least two prior therapies, including
a purine nucleoside analog.3 The primary
endpoint of the trial was durable complete response.3 Summary of key
results from the trial, as determined by a blinded independent
central review:2
|
Efficacy measure
|
Result %, (95% CI)
|
|
Durable
complete response ratea,b
|
30%
(20, 41)
|
|
Overall
response ratec
|
75%
(64, 84)
|
|
Complete response
rated
|
41%
(30, 53)
|
|
Partial
response ratee
|
34%
(24, 45)
|
|
Haematologic
remission rateb
|
80%
|
|
a
|
Durable complete response is defined as patients who achieved
complete response with haematologic remission for a duration of
more than 180 days
|
|
b
|
Haematologic remission is defined as
haemoglobin > 11g/dL,
neutrophils > 1500/mm3,
platelets > 100,000/mm3 without
transfusions or growth factor for at least 4
weeks
|
|
c
|
Overall response rate is defined as best overall response of
complete response or partial response
|
|
d
|
Complete response is defined as clearing of the bone marrow of
hairy cells by routine haematoxylin and eosin stain, radiologic
resolution of pre-existing lymphadenopathy and/or organomegaly, and
haematologic remission
|
|
e
|
Partial response is defined as ≥ 50% decrease or
normalisation (< 500/mm3)
in peripheral blood lymphocyte count, reduction of pre-existing
lymphadenopathy and/or organomegaly, and haematologic
remission
|
The median time to haematologic remission was 1.1 months (range:
0.2 to 13).2 At
data cut-off, the median duration of complete response was not yet
reached after a median 16.7 months of follow-up.2
Capillary leak syndrome (CLS) and haemolytic uraemic syndrome
(HUS), including life-threatening cases of each, have been reported
among patients treated with Lumoxiti. In the combined safety database of 129 HCL
patients treated with Lumoxiti, Grade 3 or 4 CLS occurred in 1.6% and 2% of
patients, respectively. Grade 3 or 4 HUS occurred in 3% and 0.8% of
patients, respectively.2
In the '1053' trial of 80 patients, the most common Grade 3 or 4
adverse reactions (reported in at least ≥ 5% of patients)
were hypertension, febrile neutropenia, and HUS. HUS was the most
common adverse reaction leading to discontinuation (5%). The most
common adverse reactions (≥ 20%) of any grade were infusion
related reactions (50%), oedema (39%), nausea (35%), fatigue (34%),
headache (33%), pyrexia (31%), constipation (23%), anaemia (21%),
and diarrhoea (21%). The most common laboratory abnormalities
(≥ 20%) of any grade were creatinine increased, ALT
increased, hypoalbuminaemia, AST increased, hypocalcaemia,
hypophosphataemia, haemoglobin decreased, neutrophil count
decreased, hyponatreamia, blood bilirubin increased, hypokalaemia,
GGT increased, hypomagnesaemia, platelet count decreased,
hyperuricaemia, and alkaline phosphate
increased.2
The recommended dose of Lumoxiti is 0.04 mg/kg administered as an intravenous
infusion over 30 minutes on days 1, 3, and 5 of each 28-day cycle
up to 6 cycles, disease progression, or unacceptable
toxicity.2
About hairy cell leukaemia
Hairy cell leukaemia (HCL) is a rare, chronic, and slow-growing
leukaemia in which the bone marrow overproduces abnormal B cell
lymphocytes.8,9 HCL
can result in serious and life-threatening conditions, including
infections, bleeding and anaemia.10 Approximately
1,000 people are diagnosed with HCL in the US each
year.11 While
many patients initially respond to treatment, 30% to 40% will
relapse five to ten years after their first
treatment.4 With
no established standard of care and very few treatments available,
there remains significant unmet medical need for people with
relapsed or refractory HCL.4,8
About Lumoxiti
Lumoxiti (moxetumomab
pasudotox, formerly CAT8015 or HA22) is a CD22-directed cytotoxin
and a first-in-class treatment in the US for adult patients with
relapsed or refractory hairy cell leukaemia (HCL) who have received
at least two prior systemic therapies, including treatment with a
purine nucleoside analog. Lumoxiti is not recommended in patients with severe
renal impairment (CrCl ≤ 29 mL/min).2 It
comprises the CD22 binding portion of an antibody fused to a
truncated bacterial toxin; the toxin inhibits protein synthesis and
ultimately triggers apoptotic cell death.2 Lumoxiti has
been granted Orphan Drug Designation by the FDA for the treatment
of HCL.
About the '1053' Phase III trial
The '1053' trial is a single-arm, multicentre Phase III clinical
trial assessing the efficacy, safety, immunogenicity and
pharmacokinetics of moxetumomab pasudotox monotherapy in patients
with relapsed or refractory HCL who have received at least two
prior therapies, including one purine nucleoside analog. The trial
was conducted in 80 patients across 34 sites in 14 countries. The
primary endpoint was durable complete response (CR), defined as CR
with haematologic remission (blood count normalisation) for >180
days. Secondary outcome measures included overall response rate,
relapse free survival, progression-free survival, time to response,
safety, pharmacokinetic and immunogenic
potential.7
Early discovery of moxetumomab pasudotox was led by the National
Cancer Institute (NCI). The collaboration between NCI and
MedImmune, AstraZeneca's global biologics research and development
arm, is an example of how scientific partnerships can lead to
important advances for cancer patients.
About AstraZeneca in Haematology
Leveraging its strength in oncology, AstraZeneca has established
haematology as one of four key oncology disease areas of focus and
is accelerating development of a broad portfolio of potential blood
cancer treatments. AstraZeneca and Acerta Pharma, its haematology
research and development centre of excellence, received US FDA
approval for the first medicine in this
franchise, Calquence (acalabrutinib), in
October 2017.
About 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 at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, we
are committed to advance Oncology as a growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to our core capabilities, we actively pursue innovative
partnerships and investments that accelerate the delivery of our
strategy, as illustrated by our investment in Acerta Pharma in
haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - 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.
About MedImmune
MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialisation of
small molecule and biologic prescription medicines. MedImmune is
pioneering innovative research and exploring novel pathways across
Oncology, Respiratory, Cardiovascular, Renal & Metabolic
Diseases, and Infection and Vaccines. The MedImmune headquarters is
located in Gaithersburg, MD, one of AstraZeneca's three global
R&D centres, with additional sites in Cambridge, UK and South
San Francisco, CA. For more information, please
visit www.medimmune.com.
About AstraZeneca
AstraZeneca 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. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide.
For more information, please visit www.astrazeneca.com and
follow us on Twitter @AstraZeneca.
|
Media
Relations
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Birmingham
|
UK/Global
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+44 203
749 5634
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Rob
Skelding
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UK/Global
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+44 203
749 5821
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Matt
Kent
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UK/Global
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+44 203
749 5906
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Gonzalo
Viña
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UK/Global
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+44 203
749 5916
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Jacob
Lund
|
Sweden
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+46
8 553 260 20
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Michele
Meixell
|
US
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+1 302
885 2677
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Investor
Relations
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Thomas
Kudsk Larsen
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+44 203
749 5712
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Henry
Wheeler
|
Oncology
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+44 203
749 5797
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Christer
Gruvris
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Cardiovascular;
Metabolism
|
+44 203
749 5711
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Nick
Stone
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Renal
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+44 203
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Adrian Kemp
Company Secretary
AstraZeneca PLC
References
|
1.
|
US Food and Drug Administration. Drugs@FDA: FDA Approved Drug
Products. Leustatin
(cladribine). Available
online. Accessed August
2018.
|
|
2.
|
Lumoxiti (moxetumomab
pasudotox-tdfk) Prescribing Information. AstraZeneca
Pharmaceuticals LP, Wilmington, DE. 2018.
|
|
3.
|
ClinicalTrials.gov. Moxetumomab Pasudotox for Advanced Hairy Cell
Leukemia. Available
Online. Accessed August 2018.
|
|
4.
|
Lopez-Rubio M, Garcia-Marco JA. Current and emerging treatment
options for hairy cell leukemia. Onco Targets
Ther.
2015;8:2147-2156. Available
online.
Accessed August 2018.
|
|
5.
|
Zinzani PL, Pellegrini C, Stefoni V, et al. Hairy cell
leukemia: evaluation of the long-term outcome in 121
patients. Cancer. 2010;116(20):4788-4792.
|
|
6.
|
Kreitman RJ, Arons E. Update on Hairy Cell Leukemia Clinical
Advances in Hematology and Oncology 2018. Clin Adv
Hematol Oncol.
2018;16(3):205-215. Available
Online.
Accessed August 2018.
|
|
7.
|
US Food and Drug Administration. Priority
Review. Available
Online.
Accessed August 2018.
|
|
8.
|
National Institutes of Health. Hairy Cell
Leukemia. Available
Online.
Accessed August 2018.
|
|
9.
|
Hairy Cell Leukemia Foundation. Hairy cell
leukemia. Available
online. Accessed August
2018.
|
|
10.
|
Hairy Cell Leukemia Foundation.
Complications. Available
Online.
Accessed August 2018.
|
|
11.
|
Troussard X, Cornet E. Hairy cell leukemia 2018: Update on
diagnosis, risk‐stratification,
and treatment. Am J
Hematol. 2017;92(12):1382-1390. Published
online November 7, 2017. Available
Online. Accessed August
2018.
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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:
14 September
2018
|
|
By: /s/
Adrian Kemp
|
|
|
Name:
Adrian Kemp
|
|
|
Title:
Company Secretary
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