a9026i
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 April 2024
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Voydeya approved in US
2 April
2024
Voydeya approved
in the US as add-on therapy to ravulizumab or eculizumab for
treatment of extravascular
haemolysis in adults with the rare disease PNH
Approval of first-in-class, oral, Factor D inhibitor based on
results from pivotal ALPHA Phase III trial
Voydeya (danicopan) has
been approved in the US as add-on therapy to ravulizumab or
eculizumab for the treatment of extravascular haemolysis (EVH) in
adults with paroxysmal nocturnal haemoglobinuria
(PNH).1 Voydeya is
a first-in-class, oral, Factor D inhibitor developed as an add-on
to standard-of-care Ultomiris (ravulizumab) or Soliris (eculizumab) to
address the needs of the approximately 10-20% of patients with PNH
who experience clinically significant EVH while treated with a C5
inhibitor.2,3
The approval by the US Food and Drug Administration (FDA) was based
on positive results from the pivotal ALPHA Phase III
trial. Results from the
12-week primary evaluation period of the trial were published
in The
Lancet Haematology.2
Bart Scott, MD, Professor, Division of Hematology and Oncology at
the University of Washington Medical Center, and Professor,
Clinical Research Division at Fred Hutchinson Cancer
Center, said:
"The
approval of Voydeya offers
this small subset of PNH patients an add-on therapy designed to
address EVH, while maintaining disease control
with Ultomiris or Soliris.
Terminal complement inhibition with Ultomiris can address the life-threatening
complications of PNH, building on the efficacy and safety
of Soliris established over nearly 20
years."
Marc Dunoyer, Chief Executive Officer, Alexion,
said: "The approval of
first-in-class, Factor D inhibitor Voydeya marks
an important advancement in the treatment of PNH and builds on our
leadership and commitment to bring forward innovation in complement
science. As the ALPHA trial suggests, dual complement pathway
inhibition at Factor D and C5 may be an optimal treatment approach
for this subset of patients with EVH, enabling them to continue
with proven standard-of-care therapy."
The ALPHA Phase III trial evaluated the efficacy and safety
of Voydeya as add-on to Ultomiris or Soliris in patients with PNH who experienced
clinically significant EVH. Results showed
that Voydeya met the primary endpoint of change in
haemoglobin from baseline to week 12 and all key secondary
endpoints, including transfusion avoidance and change in Functional
Assessment of Chronic Illness Therapy -
Fatigue (FACIT-Fatigue) score.2
Results from the ALPHA Phase III trial
showed Voydeya was generally well tolerated, and no new
safety concerns were identified. In the trial, the most common
treatment-emergent adverse events were headache, nausea, arthralgia
and diarrhoea.2
Voydeya has been granted
Breakthrough Therapy designation by the US FDA and PRIority
MEdicines (PRIME) status by the European Medicines
Agency. Voydeya has also been granted Orphan Drug
Designation in the US, European Union (EU) and Japan for the
treatment of PNH. Voydeya has been approved in
Japan and recommended for
approval in the EU. Regulatory reviews are ongoing in
additional countries.
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).4-6
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.4 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.4,7,8
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.9,10 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.4,6,11 PNH
patients with EVH may continue to experience anaemia, which can
have various causes, and may require blood
transfusions.9,10,12,13 A
small subset of people living with PNH who are treated with a C5
inhibitor experience clinically significant EVH, which results in
continued symptoms of anaemia and may require blood
transfusions.4,7,14,15
ALPHA
ALPHA is a pivotal, global Phase III trial designed as a
superiority study to evaluate the efficacy and safety
of Voydeya as an add-on to C5 inhibitor
therapy Soliris or Ultomiris 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 Voydeya or placebo (2:1) in addition to their
ongoing Soliris or Ultomiris therapy for 12 weeks. A prespecified interim
analysis was performed once 63 randomised patients had completed 12
weeks of the primary evaluation period or discontinued treatment as
of June 28, 2022. At 12 weeks, patients on placebo
plus Soliris or Ultomiris were switched to Voydeya plus Soliris or Ultomiris, and patients on Voydeya plus Soliris or Ultomiris remained on this treatment for an additional
12 weeks. Patients who completed both treatment periods (24 weeks)
had the option to participate in a two-year long-term extension
period and continue to receive Voydeya in addition to Soliris or Ultomiris. The open-label period of the study is
ongoing.2,16
Voydeya (danicopan)
Voydeya (danicopan) is
a first-in-class oral Factor D inhibitor. The medication works
by selectively inhibiting Factor D, a complement system protein
that plays a key role in the amplification of the complement system
response. When activated in an uncontrolled manner, the
complement cascade over-responds, leading the body to attack its
own healthy cells. Voydeya has been granted Breakthrough Therapy
designation by the US Food and Drug Administration and PRIority
MEdicines (PRIME) status by the European Medicines
Agency. Voydeya has also been granted Orphan Drug
Designation in the US, EU and Japan for the treatment of
PNH.
Voydeya is approved in the
US as add-on therapy to ravulizumab or eculizumab for the treatment
of EVH in adults with PNH.
Voydeya is also approved
in Japan for certain adults with PNH in combination with C5
inhibitor therapy.
Alexion is also evaluating Voydeya 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 more
than 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 70 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 social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team,
please click here.
For Media contacts, click here.
References
1. Voydeya (danicopan) US prescribing information;
March 2024.
2. Lee JW, et al. Addition of
danicopan to ravulizumab or eculizumab in patients with paroxysmal
nocturnal haemoglobinuria and clinically significant extravascular
haemolysis (ALPHA): a double-blind, randomised, phase 3
trial. The Lancet
Haematology. 2023;10(12):E955-E965.
3.
Kulasekararaj AG, et al. Prevalence of clinically significant
extravascular hemolysis in stable C5 inhibitor-treated patients
with PNH and its association with disease control, quality of life
and treatment satisfaction. Presented at: European Hematology
Association (EHA) Hybrid Congress. 8-11 June 2023; Frankfurt,
Germany. Abs PB2056.
4. Brodsky RA. Paroxysmal nocturnal
hemoglobinuria. Blood. 2014;124(18):2804-2811.
5. Griffin M, et al. Significant
hemolysis is not required for thrombosis in paroxysmal nocturnal
hemoglobinuria. Haematologica.
2019;104(3):E94-E96.
6. Hillmen P, et al. The complement
inhibitor eculizumab in paroxysmal nocturnal
hemoglobinuria. N Engl J
Med.
2006;355(12):1233-1243.
7. Kulasekararaj AG, et al.
Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced
adult patients with PNH: the 302 study. Blood. 2019;133(6):540-549.
8. Hillmen P, et al. Effect of the
complement inhibitor eculizumab on thromboembolism on patients with
paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128.
9. Brodsky RA. A complementary new
drug for PNH. Blood. 2020;135(12):884-885.
10. Risitano AM, et al. Anti-complement
treatment for paroxysmal nocturnal hemoglobinuria: time for
proximal complement inhibition? A position paper from the SAAWP of
the EBMT. Front
Immunol.
2019;10:1157.
11. Kulasekararaj AG, et al. Long-term
safety and efficacy of ravulizumab in patients with paroxysmal
nocturnal hemoglobinuria: 2-year results from two pivotal phase 3
studies. Eur J
Haematol.
2022;109(3):205-214.
12. Berentsen S, et al. Novel insights into
the treatment of complement-mediated hemolytic
anemias. Ther Adv
Hematol. 2019;10:2040620719873321.
13. Kulasekararaj AG, et al. Monitoring of
patients with paroxysmal nocturnal hemoglobinuria on a complement
inhibitor. Am J
Hematol. 2021;96(7):E232-E235.
14. Lee JW, et al. Ravulizumab (ALXN1210) vs
eculizumab in adult patients with PNH naive to complement
inhibitors: the 301 study. Blood. 2019;133(6):530-539.
15.
Röth A, et al. Transfusion requirements in adult patients with
paroxysmal nocturnal hemoglobinuria naive to complement inhibitors
receiving ravulizumab and eculizumab: results from a phase 3
non-inferiority study [abstract]. ECTH 2019. Glasgow, UK ed.
Glasgow, UK2019.
16. ClinicalTrials.gov.
Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal
Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically
Evident Extravascular Hemolysis (EVH)(ALPHA). NCT Identifier:
NCT04469465. Available here.
Accessed March 2024.
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:
2 April
2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
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