Danicopan (ALXN2040) add-on to Ultomiris or Soliris met primary endpoint in ALPHA Phase III trial for patients with paroxysmal nocturnal haemoglobinuria who experience clinically significant extravascular haemolysis

Interim results demonstrate statistically significant improvement compared to placebo in haemoglobin levels from baseline to week 12

A prespecified interim analysis of the ALPHA Phase III trial evaluating danicopan (ALXN2040), an investigational, oral factor D inhibitor, as an add-on to C5 inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab) showed positive high-level results in patients with paroxysmal nocturnal haemoglobinuria (PNH) who experience clinically significant extravascular haemolysis (EVH).

The trial met its primary endpoint of change in haemoglobin from baseline at 12 weeks and key secondary endpoints, including transfusion avoidance and change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score. Danicopan plus Ultomiris or Soliris demonstrated superiority compared to placebo plus Ultomiris or Soliris for this specific patient population, with statistically significant and clinically meaningful improvements in haemoglobin levels, transfusion avoidance and FACIT Fatigue scores from baseline.

PNH is a rare and severe blood disorder characterised by the destruction of red blood cells, known as intravascular haemolysis (IVH), and white blood cell and platelet activation that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.1-3

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Alexion has relentlessly innovated for the PNH community, pioneering with Soliris, the first treatment for PNH, and establishing Ultomiris as a standard of care. We are proud of our continued innovation to advance new ways of targeting the complement cascade to help address the needs of patients living with this debilitating disease. These are the first positive Phase III results for an oral factor D inhibitor and demonstrate the potential for danicopan add-on therapy to improve signs and symptoms and reduce the need for transfusions for the limited proportion of people living with PNH who experience clinically significant EVH.”

Professor Jong-Wook Lee, MD, PhD, Department of Haematology at Seoul St. Mary’s Hospital of The Catholic University of Korea, and investigator in the ALPHA trial, said: “C5 inhibitors are a proven treatment option for patients living with PNH, yet a small percentage may continue to experience anaemia and burden of transfusion due to clinically significant EVH, however it is not life-threatening. These data show that danicopan has the potential to resolve clinically significant EVH while allowing patients to remain on standard of care treatment with Ultomiris or Soliris.”

Danicopan was generally well tolerated and there were no clinically meaningful differences in safety results observed between the danicopan plus C5 inhibitor group and control group.

Alexion, AstraZeneca Rare Disease, will present these data at a forthcoming medical meeting and intends to proceed with regulatory submissions in the coming months.

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