REG - AstraZeneca PLC - Voydeya approved in US

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02/04/2024 07:15

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RNS Number : 8967I  AstraZeneca PLC  02 April 2024

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
(https://www.astrazeneca.com/media-centre/press-releases/2023/danicopan-as-add-on-to-ultomiris-or-soliris-improved-haemoglobin-levels-and-maintained-disease-control-in-patients.html)
. Results from the 12-week primary evaluation period of the trial were
published in The Lancet Haematology
(https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(23)00315-0/fulltext)
.(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
(https://www.astrazeneca.com/media-centre/press-releases/2024/voydeya-danicopan-granted-first-ever-regulatory-approval-in-japan-for-adults-with-pnh-to-be-used-in-combination-with-c5-inhibitor-therapy.html)
and recommended for approval in the EU
(https://www.astrazeneca.com/media-centre/press-releases/2024/voydeya-recommended-for-eu-approval.html)
. 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 (http://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca) .

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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 (https://clinicaltrials.gov/ct2/show/NCT04469465) . Accessed
March 2024.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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