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 November
2019
Commission
File Number: 001-11960
AstraZeneca PLC
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Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Anifrolumab
demonstrated superiority across multiple efficacy endpoints in
patients with systemic lupus erythematosus in Phase III TULIP 2
trial
12
November 2019 07:00 GMT
Anifrolumab
demonstrated superiority across multiple efficacy
endpoints
in patients with systemic lupus erythematosus in Phase III TULIP 2
trial
Anifrolumab achieved a statistically significant
reduction
in disease activity, a statistically significant reduction in
oral
corticosteroid use and improvement in skin
manifestations
AstraZeneca
today presented detailed results from the positive Phase III TULIP
2 trial for anifrolumab, a potential new medicine for the treatment
of moderate to severe systemic lupus erythematosus (SLE),
which demonstrated superiority across multiple efficacy endpoints
versus placebo, with both arms receiving standard of
care.
On the primary endpoint, anifrolumab achieved a
statistically significant and clinically meaningful reduction in
disease activity at week 52, with 47.8% of patients receiving
anifrolumab responding compared with 31.5% of patients on placebo,
as measured by the British Isles Lupus Assessment Group-based
Composite Lupus Assessment (BICLA) composite
measure.1 The
positive BICLA result in TULIP 2 is consistent with results from
pre-specified analyses using the BICLA endpoint in the Phase III
TULIP 12,3 and
the Phase II MUSE trials.4
The TULIP 2 trial also showed statistically significant differences
in multiple secondary endpoints.1 51.5%
of anifrolumab patients receiving oral corticosteroids (OCS)
greater than or equal to 10mg achieved a sustained reduction
in OCS use compared with 30.2% of patients on placebo.
Additionally, 49% of patients receiving anifrolumab with moderate
to severe skin disease experienced improved skin
manifestations at week 12, the pre-specified timepoint, compared
with 25% of patients receiving placebo. Skin manifestations were
measured by the Cutaneous Lupus Erythematosus Disease Area and
Severity Index (CLASI).
Mene Pangalos, Executive Vice President, BioPharmaceuticals
R&D, said: "There has only been one new medicine approved for
systemic lupus erythematosus in the last 60 years, which is why we
are so excited to see the positive TULIP 2 results. There is now a
strong body of evidence demonstrating the benefit of anifrolumab,
and we look forward to bringing this potential new medicine to
patients with systemic lupus erythematosus as soon as
possible."
Professor Eric F. Morand, Monash University, Australia, and
Principal Investigator on the TULIP 2 trial, said: "Systemic lupus
erythematosus is often difficult to treat, and innovative new
therapies are urgently needed. The TULIP 2
results demonstrated that, by targeting the type I interferon
receptor, anifrolumab reduces overall disease activity,
reduces corticosteroid use and improves skin
manifestations."
Dr. Richard Furie, Chief of the Division of Rheumatology at
Northwell Health, New York, US, and Principal Investigator on the
TULIP 1 trial and the Phase II
MUSE trial, said: "The results across the MUSE and TULIP trials are
very important because they support anifrolumab's potential to
address systemic lupus erythematosus, an often
devastating disease that can impact almost any organ and even
lead to long-term organ damage and
death."
The TULIP data are being presented at the American
College of Rheumatology (ACR) Annual Meeting 2019 in Atlanta, US.
The TULIP 1 data were also published simultaneously
in The
Lancet Rheumatology.
As previously disclosed, TULIP 1 did not meet its
primary endpoint based on the SLE Responder Index 4 (SRI4)
composite measure. However, analyses of secondary endpoints
show efficacy consistent with TULIP 2 on BICLA response, reduction
in OCS use, and improvement in skin disease
activity.2,3
The safety and tolerability findings in TULIP 1 and TULIP 2 were
consistent with the known profile of
anifrolumab.1,2,3 There
were more commonly reported cases of herpes zoster in patients on
anifrolumab (TULIP 1: 5.6% vs.1.6%, TULIP 2: 7.2% vs.1.1%). Most
cases were mild to moderate in severity and all were cutaneous and
resolved with antiviral treatment.
About anifrolumab
Anifrolumab is a fully human monoclonal antibody that binds to
subunit 1 of the type I interferon receptor, blocking the activity
of all type I interferons including IFN-alpha, IFN-beta and
IFN-omega.4 Type
I interferons are cytokines involved in the inflammatory
pathways.5 Between
60% and 80% of adults with SLE have an increased type I interferon
gene signature, which has been shown to correlate with disease
activity.5,6
AstraZeneca acquired global rights to anifrolumab through an
exclusive license and collaboration agreement with Medarex, Inc. in
2004. Medarex was acquired by Bristol-Myers Squibb in
2009.
About TULIP
The pivotal TULIP (Treatment of Uncontrolled Lupus via the
Interferon Pathway) programme includes two Phase III clinical
trials, TULIP 1 and TULIP 2, that evaluated the efficacy and safety
of anifrolumab versus placebo in patients with moderately to
severely active autoantibody-positive SLE who are receiving
standard of care treatment.
TULIP 1 randomised 457 eligible patients (1:2:2) to receive a
fixed-dose intravenous infusion of 150mg anifrolumab, 300mg
anifrolumab, or placebo every four weeks. TULIP 1 assessed the
effect of anifrolumab in reducing disease activity as measured by
the SRI4.
TULIP 2 randomised 365 eligible patients (1:1) to receive a
fixed-dose intravenous infusion of 300mg anifrolumab or placebo
every four weeks. TULIP 2 assessed the effect of anifrolumab in
reducing disease activity as measured by the BICLA.
The SRI4 and the BICLA are both validated composite measures of SLE
disease activity, which have been used as primary endpoints in
Phase III lupus trials.7 Each
contain the same disease activity assessment tools, British Isles
Lupus Assessment Group (BILAG) index and Systemic Lupus
Erythematosus Disease Activity Index 2000 (SLEDAI-2K), but utilise
different scoring systems.7 The
BICLA requires improvement in all organs with disease activity from
baseline, with no new flares. It can capture clinically meaningful
partial improvements within an organ system. The SRI4 requires
complete resolution in a single 'higher weight' lupus symptom or
complete resolution in multiple 'lower weight' lupus symptoms, with
no new flares. It does not require improvement across all affected
organ systems.
In addition to the pivotal Phase III TULIP programme, anifrolumab
is being evaluated in a Phase III long-term extension trial in SLE
and a Phase II trial in lupus nephritis.
About SLE
Systemic lupus erythematosus (SLE) is an autoimmune disease in
which the immune system attacks healthy tissue in the
body.8 It
is a chronic and complex disease with a variety of clinical
manifestations that can impact many organs and can cause a
range of symptoms including pain, rashes, fatigue, swelling in
joints, and fevers.9 It
is associated with a greater risk of death from causes such as
infection and cardiovascular disease.10 There
has been only one new medicine approved for SLE in the last 60
years.11
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 and
Metabolism, and Respiratory. 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.
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References
1. Morand E, Furie R, Tanaka Y,
et al. Efficacy and Safety of Anifrolumab in Patients with
Moderate to Severe Systemic Lupus Erythematosus: Results of the
Second Phase 3 Randomized Controlled Trial [oral]. Presented at:
ACR 2019 Annual Meeting; November 8-13, 2019. Abstract ID:
757228. https://acrabstracts.org/abstract/efficacy-and-safety-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus-results-of-the-second-phase-3-randomized-controlled-trial/ Accessed:
November, 2019.
2. Furie R, Morand E, Bruce
I, et al. A Phase 3 Randomized Controlled Trial of
Anifrolumab in Patients With Moderate to Severe Systemic Lupus
Erythematosus. Presented at: ACR 2019 Annual Meeting; November
8-13, 2019. Abstract ID: 1763. https://acrabstracts.org/abstract/a-phase-3-randomized-controlled-trial-of-anifrolumab-in-patients-with-moderate-to-severe-systemic-lupus-erythematosus/. Accessed:
October, 2019.
3. Furie R, Morand E, Bruce I, et
al. Anifrolumab: Type I Interferon Inhibitor Anifrolumab in Active
Systemic Lupus Erythematosus (TULIP-1): a Randomised, Controlled
Phase 3 Trial, Lancet
Rheumatology 2019;
doi.org/10.1016/S2665-9913(19)30076-1. Accessed November 11,
2019.
4. Furie R, Khamashta M, Merrill
J.T, et al. Anifrolumab, an Anti-Interferon‐a
Receptor Monoclonal Antibody, in Moderate‐to‐Severe
Systemic Lupus Erythematosus. Arthritis &
Rheumatology. 2017;69(2);376-386.
5. Lauwerys, B.R., Ducreux J,
Houssiau F.A., et al. Type I Interferon Blockade in Systemic
Lupus Erythematosus: Where Do We Stand? Rheumatology.
2013;53(8);1369-1376.
6. Crow, M. K., Type I Interferon in
the Pathogenesis of Lupus, The Journal of
Immunology.
2014;192(12);5459-5468.
7. Mikdashi J, Nived O. Measuring
Disease Activity in Adults with Systemic Lupus Erythematosus: The
Challenges of Administrative Burden and Responsiveness to Patient
Concerns in Clinical Research. Arthritis Research &
Therapy 2015;17(1):183.
8. The Lupus Foundation of America.
Available at https://resources.lupus.org/entry/what-is-lupus?utm_source=lupusorg&utm_medium=answersFAQ.
Accessed November 2019.
9. ACR. Guidelines for Referral and
Management of Systemic Lupus Erythematosus in Adults. American
College of Rheumatology Ad Hoc Committee on Systemic Lupus
Erythematosus Guidelines, Arthritis &
Rheumatism. 1999; 42;
1785-1796.
10. Nossent J, Cikes N, Kiss E, et
al. Current Causes of Death in Systemic Lupus Erythematosus in
Europe, 2000-2004: Relation to Disease Activity and Damage
Accrual. Lupus.16(5), 309-317.
11. Mahieu M. A., Strand V, Simon Lee
S., et al. A Critical Review of Clinical Trials in Systemic
Lupus Erythematosus. Lupus. 2016;25(10);1122-1140.
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:
12 November
2019
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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