Regulatory Decision Summary for Voydeya

The purpose of this new drug submission (NDS) was to gain market authorization, pursuant to section C.08.004 of the Food and Drug Regulations, for Voydeya (danicopan) 50 mg and 100 mg oral tablets.

This submission was filed to seek approval for the following indication: as an add-on to Ultomiris or Soliris for the treatment of signs or symptoms of extravascular hemolysis (EVH) in adult patients with paroxysmal nocturnal hemoglobinuria (PNH).

The Sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder in which a deficiency of complement regulatory proteins on red blood cells leads to paroxysmal hemolysis and a propensity for thrombosis, organ dysfunction, and bone marrow failure. Although the standard-of-care C5 inhibitor therapies have improved outcomes related to the control of intravascular hemolysis (IVH), some patients continue to experience extravascular hemolysis (EVH) resulting in persistent anemia.

Clinical efficacy and safety for the proposed indication were supported primarily by a randomized, double-blind, placebo-controlled trial to evaluate the addition of danicopan to a C5 inhibitor (ravulizumab or eculizumab) in patients with PNH and anemia. A total of 86 adult patients were randomized to receive either danicopan 150 mg orally three times a day orally or matching placebo, in addition to continuing treatment with their background C5 inhibitor.

The primary endpoint was change in hemoglobin relative to baseline after 12 weeks of treatment with danicopan compared to placebo. A statistically significant and clinically meaningful improvement was observed with danicopan compared to placebo, with a least squares mean difference of 2.4 g/dL. Results were generally consistent regardless of age, sex, number of transfusions prior to screening, hemoglobin level at screening, or background C5 inhibitor.

Statistically significant and clinically meaningful secondary endpoints at the end of the 12-week assessment period included the proportion of patients who had both a hemoglobin increase of ≥ 2.0 g/dL and transfusion avoidance, proportion of participants with transfusion avoidance, change from baseline in FACIT-Fatigue scores, and change from baseline in absolute reticulocyte counts.

Treatment-emergent adverse events reported in ≥ 3% of patients and at higher incidence than in the placebo arm in the first 12 weeks were: headache, hepatic enzyme increased, vomiting, arthralgia, pyrexia, hypertension, pain in extremity, hemolysis, constipation, pancreatitis, COVID-19, urinary tract infection, viral infection, blood bilirubin increased, white blood cell count decreased, myalgia, oropharyngeal pain, and rhinorrhea.

Significant safety risks for Voydeya include serious infections caused by encapsulated bacteria, hepatotoxicity, hemolysis upon treatment discontinuation, and increases in serum lipids, all of which have been added to the Warnings and Precautions section of the Voydeya Product Monograph. The primary tool for risk mitigation is the Voydeya Product Monograph.

A Risk Management Plan (RMP) for Voydeya was submitted by Alexion Pharma Canada to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will put in place to minimise risks associated with the product.

Labelling documents conform to the necessary regulatory requirements and are consistent with the labelling guidance documents. The submission was considered acceptable with respect to the labelling documents reviewed.

This submission is considered to comply with the Quality data requirements of Section C.08.002 of the Food and Drug Regulations.

The initial proposed indication was as an add-on to ravulizumab or eculizumab for the treatment of signs or symptoms of extravascular hemolysis (EVH) in adult patients with PNH. The indication was changed to the treatment of adult patients with PNH who have residual hemolytic anemia due to extravascular hemolysis, to reflect the nature of study participants who were required to have anemia (hemoglobin ≤ 9.5 g/dL) for study entry.

Overall, treatment with Voydeya as an add-on to ravulizumab or eculizumab demonstrated significant improvements in hemoglobin in patients with PNH who have residual hemolytic anemia due to extravascular hemolysis. Addition of Voydeya to a C5 inhibitor was associated with a manageable safety profile.

Therefore, the benefit-risk is considered positive under the agreed-on conditions of use.

For further details about Voydeya, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.