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 (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.
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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.
Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811.
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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.
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.
Berentsen S, et al. Novel insights into the treatment of complement-mediated hemolytic anemias. Ther Adv Hematol. 2019;10:2040620719873321.
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.

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