ALPHA Phase III trial showed first-in-class,
oral, Factor D inhibitor as add-on to Ultomiris or Soliris improved
hemoglobin levels and reduced anemia and fatigue
MISSISSAUGA, ON, July 23,
2024 /CNW/ - Voydeya (danicopan tablets)
has been approved in Canada as an add-on to ravulizumab or
eculizumab for the treatment of adult patients with paroxysmal
nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia
due to extravascular hemolysis
(EVH).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 extravascular hemolysis (EVH) while treated
with a C5 inhibitor.2,3
The Notice of Compliance issued by Health Canada is based on the
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
Dr. Christopher Patriquin, Chair
of the Canadian PNH Network and Assistant Professor of Medicine
(Hematology) at the University of
Toronto and Clinician Investigator at the University Health
Network said: "The approval of danicopan, an oral add-on
therapy to ravulizumab or eculizumab, means that the subset of
patients with PNH who have clinically significant extravascular
hemolysis now have a new therapeutic strategy available to them.
Dual complement inhibition can enable patients to remain on our
current standard of care C5 inhibition to maintain disease control,
while increasing hemoglobin and potentially further improving their
quality of life."
Barry Katsof, Founder and
President of the Canadian Association of PNH Patients, said: "This
is very exciting news for Canadian PNH patients, as the approval of
Voydeya now offers the subset of patients experiencing
extravascular hemolysis while treated with eculizumab or
ravulizumab an add-on therapy designed to address this condition
and improve their quality of life."
Karen Heim, General Manager of
Alexion Canada, said: "People living
with a rare disease and their families deserve our unwavering
commitment to developing and enabling access to therapies that can
help them live longer, fuller lives. The approval of Voydeya
is a testament to Alexion's commitment to continuous innovation,
particularly in areas of great unmet need."
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 hemoglobin 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 diarrhea.2
Voydeya has been granted Breakthrough Therapy
designation by the United States
(US) Food and Drug Administration (FDA) and PRIority MEdicines
(PRIME) status by the European Medicines Agency
(EMA). Voydeya has also been granted Orphan Drug
Designation in the US, EU and Japan for the treatment of
PNH. Voydeya has been approved in the US,
EU and Japan,
and regulatory reviews are ongoing in additional
countries.
Notes
PNH
PNH is a rare, chronic, progressive and
potentially life-threatening blood disorder. It is characterized by
red blood cell destruction within blood vessels (also known as
intravascular hemolysis) 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 defense 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, anemia and dark-colored
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 anemia, 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 anemia 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
randomized 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
randomized 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 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, EU, and Japan as add-on therapy to ravulizumab or
eculizumab for the treatment of certain adults with PNH.
Alexion is also evaluating Voydeya as a
potential monotherapy for geographic atrophy in a Phase II clinical
trial.
Alexion
Alexion, AstraZeneca Rare Disease is focused
on serving patients and families affected by rare diseases and
devastating conditions through the discovery, development and
delivery of life-changing medicines. A pioneering leader in rare
disease for more than three decades, Alexion was the first to
translate the complex biology of the complement system into
transformative medicines, and today it continues to build a
diversified pipeline across disease areas with significant unmet
need, using an array of innovative modalities. As part of
AstraZeneca, Alexion is continually expanding its global geographic
footprint to serve more rare disease patients around the world. It
is headquartered in Boston,
US.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a
global, science-led biopharmaceutical company that focuses on the
discovery, development and commercialization 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 www.astrazeneca.ca and follow the Company on X
@AstraZenecaCA.
References
- Voydeya (danicopan) Health Canada approved product
monograph; July 2024.
- 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.
- 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.
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- Hillmen P, et al. Effect of the complement inhibitor eculizumab
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- Brodsky RA. A complementary new drug for
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- Risitano AM, et al. Anti-complement treatment for paroxysmal
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- Kulasekararaj AG, et al. Long-term safety and efficacy of
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- Berentsen S, et al. Novel insights into the treatment of
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- Kulasekararaj AG, et al. Monitoring of patients with paroxysmal
nocturnal hemoglobinuria on a complement inhibitor. Am J
Hematol. 2021;96(7):E232-E235.
- 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.
- 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.
- 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
April 2024.
SOURCE AstraZeneca