RARE Daily

FDA Approves AstraZeneca’s Voydeya as Add-on Therapy for Extravascular Hemolysis in Adults with PNH

April 1, 2024

Rare Daily Staff

The U.S. Food and Drug Administration approved AstraZeneca’s Voydeya as an add-on therapy to Ultomiris or Soliris for the treatment of extravascular hemolysis in adults with paroxysmal nocturnal hemoglobinuria, a rare, chronic, progressive and potentially life-threatening blood disorder.

Paroxysmal nocturnal hemoglobinuria (PNH) 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 blood clots. 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. 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.

Extravascular hemolysis (EVH), the removal of red blood cells outside of the blood vessels, can sometimes occur in PNH patients who are treated with C5 inhibitors. 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. PNH patients with EVH may continue to experience anemia, which can have various causes, and may require blood transfusions. 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.

Voydeya is a first-in-class, oral, Factor D inhibitor developed by AstraZeneca’s Alexion Rare Disease as an add-on to standard-of-care Ultomiris (ravulizumab) or Soliris (eculizumab) to address the needs of the approximately 10 to 20 percent of patients with PNH who experience clinically significant EVH while treated with a C5 inhibitor.

FDA approval was based on positive results from the pivotal ALPHA phase 3 trial. Results from the 12-week primary evaluation period of the trial were published in The Lancet Haematology.

The ALPHA phase 3 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. 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.

Voydeya has been granted Breakthrough Therapy designation by the FDA and PRIority MEdicines (status by the European Medicines Agency. Voydeya has also been granted Orphan Drug designation in the U.S., European Union, and Japan for the treatment of PNH. Voydeya has been approved in Japan and recommended for approval in the EU. Regulatory reviews are ongoing in additional countries.

“The approval of first-in-class, Factor D inhibitor Voydeya marks an important advancement in the treatment of PNH,” said Marc Dunoyer, CEO Alexion Rare Disease. “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.”

Photo: Marc Dunoyer, CEO Alexion Rare Disease



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