Voydeya (danicopan) approved in the US as add-on therapy to ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH) with extravascular hemolysis (EVH). ALPHA Phase III trial showed efficacy, meeting primary and secondary endpoints. Safety profile includes common adverse events. Restricted program due to infection risk, with Boxed Warning for serious infections.

United Kingdom: Voydeya (danicopan) has gained approval in the United States as an adjunctive therapy to ravulizumab or eculizumab for treating extravascular hemolysis (EVH) in adults diagnosed with paroxysmal nocturnal hemoglobinuria (PNH). This innovative treatment, a first-in-class oral Factor D inhibitor, is designed to complement standard-of-care Ultomiris (ravulizumab) or Soliris (eculizumab), addressing the needs of the 10-20% of PNH patients who experience clinically significant EVH while on a C5 inhibitor.

The approval from the US Food and Drug Administration (FDA) was based on promising outcomes from the pivotal ALPHA Phase III trial, with results from the 12-week primary evaluation period published in The Lancet Haematology.

During the ALPHA Phase III trial, Voydeya's efficacy and safety were evaluated as an addition to Ultomiris or Soliris in patients with PNH experiencing clinically significant EVH. The trial demonstrated Voydeya's effectiveness in meeting the primary endpoint of hemoglobin change from baseline to week 12, as well as achieving key secondary endpoints such as transfusion avoidance and improvements in the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score.

The trial also indicated that Voydeya was generally well-tolerated, with common treatment-emergent adverse events including headache, nausea, arthralgia, and diarrhea. Notably, there were no new safety concerns identified.

Voydeya has received Breakthrough Therapy designation from the US FDA and PRIority MEdicines (PRIME) status from the European Medicines Agency. Additionally, it has been granted Orphan Drug Designation in the US, European Union (EU), and Japan for PNH treatment. While already approved in Japan and recommended for approval in the EU, regulatory reviews are ongoing in other countries.

Functionally, Voydeya binds reversibly to complement factor D, selectively inhibiting the alternative complement pathway. In PNH patients, Voydeya specifically targets C3 fragment-mediated EVH, while co-administered ravulizumab or eculizumab (both C5 inhibitors) are expected to continue controlling membrane attack complex-mediated intravascular hemolysis.

This approval was based on data from the double-blind, placebo-controlled phase 3 ALPHA trial (ClinicalTrials.gov Identifier: NCT04469465), involving 63 adults with PNH and clinically significant EVH. These patients were already on a stable dose of ravulizumab or eculizumab for at least the previous 6 months.

Participants were randomly assigned to receive danicopan 150mg orally three times daily (escalated to 200mg depending on response) or placebo for 12 weeks, alongside ravulizumab or eculizumab. After 12 weeks, all patients received danicopan up to week 24 with their existing treatment.

Results showed that danicopan treatment met the primary endpoint with a significant mean increase in hemoglobin from baseline to week 12 compared to placebo (2.9g/dL vs 0.5g/dL; treatment difference, 2.4g/dL [95% CI, 1.7-3.2]; P =.0007).

The commonly reported adverse reaction (≥10% incidence) was headache. The prescribing information includes a Boxed Warning due to an increased risk of serious and life-threatening infections caused by encapsulated bacteria, including Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type B.

Given this risk, Voydeya is available only through a restricted program known as Voydeya REMS. Vaccination against encapsulated bacteria or antibacterial drug prophylaxis (in patients not up to date with vaccines) is recommended. The treatment is contraindicated in individuals with unresolved serious infections.

Bart Scott, MD, Professor, Division of Hematology and Oncology at the University of Washington Medical Center, and Professor, Clinical Research Division at Fred Hutchinson Cancer Center, said, “The approval of Voydeya offers this small subset of PNH patients an add-on therapy designed to address EVH, while maintaining disease control with Ultomiris or Soliris. Terminal complement inhibition with Ultomiris can address the life-threatening complications of PNH, building on the efficacy and safety of Soliris established over nearly 20 years.”

Marc Dunoyer, Chief Executive Officer, Alexion, said, “The approval of first-in-class, Factor D inhibitor Voydeya marks an important advancement in the treatment of PNH and builds on our leadership and commitment to bring forward innovation in complement science. 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.”

According to TechSci Research, The FDA approval of Voydeya (danicopan) as an add-on therapy to ravulizumab or eculizumab for treating extravascular hemolysis (EVH) in adults with paroxysmal nocturnal hemoglobinuria (PNH) has significant implications for the healthcare market globally. Firstly, this approval expands treatment options for a subset of PNH patients who experience clinically significant EVH despite being on standard C5 inhibitors. This could potentially improve patient outcomes and quality of life, offering a tailored approach to managing this rare disease. In terms of market impact, the approval positions Voydeya as a novel addition to the PNH treatment landscape, providing a competitive edge for the pharmaceutical company behind its development. This differentiation could lead to increased market share and revenue growth, especially considering Voydeya's Orphan Drug Designation and Breakthrough Therapy designation.

Additionally, the approval sets a precedent for similar innovative therapies targeting rare diseases, encouraging further research and development in this space. From a global perspective, this approval may also influence regulatory decisions in other countries, potentially paving the way for Voydeya's approval in additional markets. This event underscores the importance of continued innovation in biopharmaceuticals and personalized medicine, driving advancements that benefit both patients and the healthcare industry.