REG - AstraZeneca PLC - Voydeya recommended for EU approval

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26/02/2024 07:00

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RNS Number : 3184E  AstraZeneca PLC  26 February 2024

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
(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)
.(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
(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 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 (http://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/?_sm_au_=iVVn0fjJ3RMtnS2jpGsWvKttvN1NG)
.

 

Contacts

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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

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

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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