▎WuXiEdited by Kant Content Team
Today, AstraZeneca announced that its "first-in-class" oral small molecule Voydeya (danicopan) has been approved by the U.S. FDA as a complement to standard therapy with complement factor C5 inhibitors.Adjunctive therapy with Ultomiris (ravulizumab) or Soliris (eculizumab),Used forTreatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) Extravascular Hemolysis in Adult Patients (EVH) Condition.
This approval is mainly based on the positive results of the randomized, double-blind ALPHA pivotal Phase 3 trial. The trial evaluated Voydeya as an add-on therapy to Ultomiris or Soliris in patients experiencing clinically significant EVH (defined as hemoglobin ≤9.5 g/dL and absolute reticulocyte count ≥120x10).9/L) in PNH patients. The results showed that,Voydeya Achieved the Primary Endpoint of Hemoglobin Change from Baseline to Week 12 and All Key Secondary Endpoints, including avoiding blood transfusions and changes in the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue) score.
Published in The Lancet Sub-Journal last DecemberThe Lancet HaematologyTheMid-term efficacy data shows,At Week 12, compared with placebo plus Ultomiris or Soliris,The least squares mean (LSM) change in hemoglobin levels from baseline significantly increased in patients receiving Voydeya plus Ultomiris or Soliris.Voydeya group was 2.94 g/dL (95% CI:2.52 to 3.36);The placebo group was 0.50 g/dL (95% CI:–0.13 to 1.12);LSM difference, 2.44 g/dL (95% CI: 1.69 to 3.20, p<0.0001).
Results from the Phase 3 ALPHA clinical trial showed that Voydeya was generally well-tolerated, with no new safety issues identified.
PNH is a rare, chronic, progressive, and potentially life-threatening blood disorder. This disease is caused by genetic mutations that result in the absence of CD55 and CD59 receptors normally present on the surface of red blood cells, leading to the activation of the alternative pathway in the complement cascade, destruction of red blood cells within blood vessels, and causing hemolysis in patients.In addition, the complement system may also activate white blood cells and platelets, leading to thrombosis. Patients experience physical weakness and symptoms such as blood clots, abdominal pain, difficulty swallowing, erectile dysfunction, shortness of breath, extreme fatigue, anemia, and dark urine. Currently, the primary treatment for PNH is the use of C5 complement inhibitors to suppress the complement reaction. However, during the course of this treatment, up to 75% of PNH patients may develop anemia, and some may even require blood transfusions.
▲Voydeya Clinical Trial Overview (Image Source: Reference [2])
Voydeya is an oral complement factor D inhibitor, designed toAdd-on medication for complement C5 inhibitor therapy in PNH patients.These patients exhibit clinically significant extravascular hemolysis symptoms. Voydeya can selectively inhibit the key complement factor D in the alternative pathway, blocking C3 convertase production and suppressing alternative pathway activity. Unlike C5 inhibitors,Voydeya prevents the deposition of C3b fragments on patients' red blood cells, controls the breakdown of red blood cells and extravascular hemolysis in PNH patients, thereby improving treatment outcomes.Currently, Voydeya has been granted Breakthrough Therapy Designation by the U.S. FDA and PRIME status by the European Medicines Agency. In addition, Voydeya has also been granted Orphan Drug Designation for the treatment of PNH in the United States, the European Union, and Japan. Previously, Voydeya had already been approved in Japan.Approval, and it has been recommended for approval in the European Union. Regulatory reviews are ongoing in other countries.
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[1] 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. Retrieved April 1, 2024 from https://www.astrazeneca.com/media-centre/press-releases/2024/voydeya-approved-in-us.htmlDisclaimer: The content team of WuXi AppTec focuses on introducing the research progress in global biopharmaceuticals and health. This article is for information exchange only, and the views expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes these views. This article is not a recommendation for treatment plans. If you need guidance on treatment options, please visit a regular hospital.Copyright Statement: This article is from the content team of WuXi AppTec. Individuals are welcome to share it on their social media circles, but unauthorized reproduction by media or institutions in any form to other platforms is prohibited. For authorization to reproduce, please reply with "reprint" on the WeChat Official Account of "WuXi AppTec" to obtain reprint guidelines.
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