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 February 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 recommended for EU approval
26 February 2024
Voydeya recommended
for approval in the EU by CHMP as add-on treatment to ravulizumab
or eculizumab for adults with PNH who have residual haemolytic
anaemia
Recommendation of first-in-class, oral, Factor D inhibitor based on
ALPHA Phase III trial results
Voydeya (danicopan) has
been recommended for marketing authorisation in the European Union
(EU) as an add-on to ravulizumab or eculizumab for the treatment of
adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who
have residual haemolytic anaemia. 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 extravascular haemolysis (EVH) while treated with a C5
inhibitor.1,2
The Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) based its positive opinion on
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.1
PNH is a rare and severe blood disorder characterised by the
destruction of red blood cells within blood vessels, 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.3-5 Immediate,
complete and sustained terminal complement inhibition by blocking
the C5 protein helps reduce symptoms and complications, resulting
in improved survival for patients with
PNH.5-8 Approximately
10-20% 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.1-3,9-11
Professor Hubert Schrezenmeier, MD, Medical Director, Institute of
Transfusion Medicine at The University of Ulm, said: "C5 inhibition
with Ultomiris or Soliris is the standard-of-care in PNH, proven to
control IVH and reduce life-threatening thrombotic events, yet a
small portion of patients may experience clinically significant
EVH. In the ALPHA trial, Voydeya as an add-on to Soliris or Ultomiris increased haemoglobin levels and reduced
fatigue, anaemia and transfusion dependence. If
approved, Voydeya may optimise care for people impacted by
this burdensome condition while allowing patients to maintain
disease control with an established C5
inhibitor."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "Today's
positive CHMP recommendation recognises the promise
of Voydeya as an add-on to standard-of-care to address
signs and symptoms of clinically significant EVH for this small
subset of patients. As we saw in the pivotal ALPHA Phase III trial,
dual complement pathway inhibition at Factor D and C5 may be an
optimal treatment approach for these patients."
The ALPHA Phase III trial evaluated the efficacy and safety
of Voydeya as an 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.1
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.1
Voydeya has been granted
Breakthrough Therapy designation by the US Food and Drug
Administration and PRIority MEdicines (PRIME) status by the
EMA. Voydeya has also been granted Orphan Drug
Designation in the US, EU and Japan for the treatment of
PNH. Voydeya was recently approved in
Japan, and regulatory
submissions for Voydeya are currently under review 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).3-5
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.3 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.3,9,12
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.13,14 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.3,5,7 PNH
patients with EVH may continue to experience anaemia, which can
have various causes, and may require blood
transfusions.13-16 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.3,9-11
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 28 June 2022. At 12 weeks, patients on placebo plus a C5
inhibitor were switched to Voydeya plus Soliris or Ultomiris,
and patients on Voydeya plus Soliris or Ultomiris remained on 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.1,17
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
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 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 social media @AstraZeneca.
Contacts
For details on how to contact the Investor Relations Team,
please click here.
For Media contacts, click here.
References
1. 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.
2.
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.
3. Brodsky RA. Paroxysmal nocturnal
hemoglobinuria. Blood. 2014;124(18):2804-2811.
4. Griffin M, et al. Significant
hemolysis is not required for thrombosis in paroxysmal nocturnal
hemoglobinuria. Haematologica.
2019;104(3):E94-E96.
5. Hillmen P, et al. The Complement
inhibitor eculizumab in paroxysmal nocturnal
hemoglobinuria. N Engl J
Med.
2006;355(12):1233-1243.
6. Lee JW, et al. The role of the
alternative pathway in paroxysmal nocturnal hemoglobinuria and
emerging treatments. Expert Rev Clin
Pharmacol.
2022;15(7):851-861.
7. 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.
8. Kulasekararaj AG, et al. P812:
Long-term complement inhibition and survival outcomes in Patients
with paroxysmal nocturnal hemoglobinuria: an interim analysis of
the ravulizumab clinical trials. HemaSphere. 2022;6(Suppl):706-707.
9. 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.
10. 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.
11.
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.
12. Hillmen P, et al. Effect of the
complement inhibitor eculizumab on thromboembolism on patients with
paroxysmal nocturnal hemoglobinuria. Blood. 2007;110(12):4123-4128.
13. Brodsky RA. A complementary new drug for
PNH. Blood. 2020;135(12):884-885.
14. 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.
15. Berentsen S, et al. Novel insights into
the treatment of complement-mediated hemolytic
anemias. Ther Adv
Hematol. 2019;10:2040620719873321.
16. Kulasekararaj AG, et al. Monitoring of
patients with paroxysmal nocturnal hemoglobinuria on a complement
inhibitor. Am J
Hematol. 2021;96(7):E232-E235.
17. 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 February 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:
26 February 2024
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|
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