In a significant development in the healthcare industry, AstraZeneca has released positive results from the 24-week and long-term extension (LTE) period of the pivotal ALPHA Phase III trial. The study focused on Danicopan as an add-on to standard of care C5 inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab). This advancement is particularly crucial for patients with paroxysmal nocturnal haemoglobinuria (PNH) who experience clinically significant extravascular haemolysis (EVH).

Sustained Clinical Improvements Observed in PNH Patients

Presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California, the data from the trial indicates sustained improvements in patients. Danicopan, a first-in-class oral Factor D inhibitor, showed that the enhancements in mean haemoglobin levels and absolute reticulocyte count (ARC) levels observed at 12 weeks were maintained through 48 weeks.

PNH: A Rare and Severe Blood Disorder

PNH is characterized by the destruction of red blood cells within blood vessels and activation of white blood cells and platelets, leading to thrombosis and potentially premature death. Immediate, complete, and sustained terminal complement inhibition by blocking the C5 protein with Ultomiris or Soliris helps reduce symptoms and complications, thereby improving survival rates. However, approximately 10-20% of patients treated with a C5 inhibitor experience clinically significant EVH, resulting in continued symptoms of anaemia and the need for blood transfusions.

Expert Opinions and Trial Design

Dr. Austin Kulasekararaj, a consultant haematologist at King’s College Hospital, London, and an investigator in the ALPHA trial, highlighted the potential of Danicopan as an add-on therapy. He emphasized the sustained improvements in haemoglobin levels for up to 48 weeks, alongside maintaining disease control. Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety at Alexion, added that dual complement pathway inhibition at Factor D and C5 may be an optimal treatment approach for patients with clinically significant EVH.

Clinical Trial Results and Patient Impact

The ALPHA Phase III trial, designed as a superiority study, evaluated the efficacy and safety of Danicopan as an add-on to C5 inhibitor therapy in patients with PNH who experience EVH. The trial involved 86 patients, with significant improvements in haemoglobin levels observed at both 12 and 24 weeks. The study also demonstrated that Danicopan is generally well-tolerated, with no new safety concerns identified.

Looking Forward: Regulatory Submissions and Potential Impact

Regulatory submissions for Danicopan are currently under review with multiple global health authorities. The results from the ALPHA Phase III trial suggest that Danicopan, in combination with existing C5 inhibitor therapies, could offer a more effective treatment approach for patients with PNH, potentially improving their quality of life and disease management.

In summary, the ALPHA Phase III trial results mark a notable advancement in the treatment of PNH, with Danicopan showing promise in addressing the needs of patients experiencing clinically significant EVH. This development underscores AstraZeneca’s commitment to advancing patient care through innovative treatments.

  AstraZeneca, danicopan, Dr. Austin Kulasekararaj, eculizumab, extravascular haemolysis, Gianluca Pirozzi, paroxysmal nocturnal haemoglobinuria, PNH, ravulizumab, SOLIRIS, Ultomiris