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 2022
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Danicopan
Phase III trial met primary endpoint
16 September 2022 07:10 BST
Danicopan (ALXN2040) add-on
to Ultomiris or Soliris met primary endpoint in ALPHA Phase III
trial for patients with paroxysmal nocturnal haemoglobinuria who
experience clinically significant extravascular
haemolysis
Interim results demonstrate statistically significant improvement
compared to placebo in haemoglobin levels from baseline to week
12
A prespecified interim analysis of the ALPHA Phase III trial
evaluating danicopan (ALXN2040), an
investigational, oral factor D inhibitor, as an add-on to C5
inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab) showed positive high-level
results in patients with paroxysmal nocturnal haemoglobinuria
(PNH) who experience clinically significant extravascular
haemolysis (EVH).
The trial met its primary endpoint of change
in haemoglobin from baseline at 12 weeks and key
secondary endpoints, including transfusion avoidance and change in
Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue
score. Danicopan plus Ultomiris or Soliris demonstrated superiority compared to placebo
plus Ultomiris or Soliris for this specific patient population, with
statistically significant and clinically meaningful improvements
in haemoglobin levels, transfusion avoidance and FACIT Fatigue
scores from baseline.
PNH is a rare and severe blood disorder characterised by the
destruction of red blood cells, known as intravascular haemolysis
(IVH), and white blood cell and platelet activation that can cause
thrombosis (blood clots) and result in organ damage and potentially
premature death.1-3
Marc Dunoyer, Chief Executive Officer, Alexion, said: "Alexion has
relentlessly innovated for the PNH community, pioneering
with Soliris, the first treatment for PNH, and
establishing Ultomiris as a standard of care. We are proud of our
continued innovation to advance new ways of targeting the
complement cascade to help address the needs of patients living
with this debilitating disease. These are the first positive Phase
III results for an oral factor D inhibitor and demonstrate the
potential for danicopan add-on therapy to improve signs and
symptoms and reduce the need for transfusions for the limited
proportion of people living with PNH who experience clinically
significant EVH."
Professor Jong-Wook Lee, MD, PhD, Department of Haematology at
Seoul St. Mary's Hospital of The Catholic University of Korea, and
investigator in the ALPHA trial, said: "C5 inhibitors are a proven
treatment option for patients living with PNH, yet a small
percentage may continue to experience anaemia and burden of
transfusion due to clinically significant EVH, however it is not
life-threatening. These data show that danicopan has the potential
to resolve clinically significant EVH while allowing patients to
remain on standard of care treatment with Ultomiris or Soliris."
Danicopan was generally well tolerated and there were no clinically
meaningful differences in safety results observed between the
danicopan plus C5 inhibitor group and control group.
Alexion, AstraZeneca Rare Disease, will present these data at a
forthcoming medical meeting and intends to proceed with regulatory
submissions in the coming months.
Notes
PNH
PNH is a rare, chronic, progressive and potentially
life-threatening blood disorder. It is characterised by red blood
cell destruction within blood vessels (also known as intravascular
haemolysis) and white blood cell and platelet activation, which can
result in thrombosis
(blood clots).1-3
PNH is caused by an acquired genetic mutation that may happen any
time after birth and results in the production of abnormal blood
cells that are missing important protective blood cell surface
proteins. These missing proteins enable the complement
system, which
is part of the immune system and is essential to the body's defence
against infection, to 'attack' and destroy or activate these
abnormal blood cells.1 Living
with PNH can be debilitating, and signs and symptoms may include
blood clots, abdominal pain, difficulty swallowing, erectile
dysfunction, shortness of breath, excessive fatigue, anaemia and
dark-coloured urine.1, 4,
5
Clinically Significant EVH
EVH, the removal of red blood cells outside of the blood vessels,
can sometimes occur in PNH patients who are treated with C5
inhibitors. Since C5 inhibition enables PNH red blood cells to
survive and circulate, EVH may occur when these now surviving PNH
red blood cells are marked by proteins in the complement system for
removal by the spleen and liver.1,3,
6 PNH patients with EVH
may continue to experience anaemia, which can have various causes,
and may require blood transfusions.6 A
small subset of people living with PNH who are treated with a C5
inhibitor experience clinically significant EVH, which can result
in continued symptoms of anaemia and require blood
transfusions.
ALPHA
ALPHA is a pivotal, global Phase III trial designed to evaluate the
efficacy of danicopan as an add-on to C5 inhibitor
therapy Ultomiris (ravulizumab) or Soliris (eculizumab) in patients with PNH who
experience clinically significant EVH. In the double-blind, placebo
controlled, multiple-dose trial, patients were enrolled and
randomised to receive danicopan or
placebo (2:1) in addition to their ongoing C5 inhibitor therapy for
12 weeks. Prespecified interim analysis for efficacy was planned
once 75 percent (N~63) of participants completed 12 weeks of
treatment period 1. At 12 weeks, patients on placebo plus C5
inhibitor are switched to danicopan plus
a C5 inhibitor and patients on danicopan plus
a C5 inhibitor remain on treatment for an additional 12
weeks.
Patients who complete both treatment periods (24 weeks) have the
option to participate in a long-term extension period and continue
to receive danicopan in
addition to C5 inhibitor therapy.
Danicopan (ALXN2040)
Danicopan is an investigational oral medicine in development as an
add-on to C5 inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab) for patients with PNH who
experience clinically significant EVH. It is designed to
selectively inhibit factor D, a complement system protein that
plays a key role in the amplification of the complement system
response. Danicopan has been granted Breakthrough Therapy
designation by the US Food and Drug Administration and PRIority
MEdicines (PRIME) status by the European Medicines Agency.
Danicopan has also been granted Orphan Drug Designation in the US
and orphan designation in the EU for the treatment of PNH. Alexion
is also evaluating danicopan as a potential monotherapy for
geographic atrophy in a Phase II clinical
trial.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca
focused on rare diseases, created following the 2021 acquisition of
Alexion Pharmaceuticals, Inc. As a leader in rare diseases for 30
years, Alexion is focused on serving patients and families affected
by rare diseases and devastating conditions through the discovery,
development and commercialisation of life-changing medicines.
Alexion focuses its research efforts on novel molecules and targets
in the complement cascade and its development efforts on
haematology, nephrology, neurology, metabolic disorders, cardiology
and ophthalmology. Headquartered in Boston, Massachusetts, Alexion
has offices around the globe and serves patients in more than 50
countries.
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 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. Brodsky RA. Paroxysmal nocturnal
hemoglobinuria. Blood. 2014;124(18):2804-2811.
2. Griffin M, Hillmen P, Munir T, et
al. Significant hemolysis is not required for thrombosis in
paroxysmal nocturnal hemoglobinuria. Haematologica.
2019;104(3):e94-e96.
3. Hillmen P., et al. The Complement
Inhibitor Eculizumab in Paroxysmal Nocturnal
Hemoglobinuria. N Engl J
Med. 2006;355(12):1233-43.
4. Hillmen, P., et al. Effect of the
complement inhibitor eculizumab on thromboembolism on patients with
paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128.
5. Kulasekararaj,
A. G., et al. Ravulizumab
(ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients
with PNH: the 302 study. Blood.
2019;133(6):540-549.
6. Brodsky RA. A complementary new
drug for PNH. Blood. 2020;135(12):884-885.
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:
16 September 2022
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
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