Alexion Reports Positive Interim Results on Combination Therapy for PNH in Late-Stage Study

A prespecified interim analysis of the ALPHA phase 3 trial evaluating danicopan (ALXN2040), an investigational, oral factor D inhibitor, as an add-on to C5 inhibitor therapy Ultomiris or Soliris showed positive high-level results in patients with paroxysmal nocturnal hemoglobinuria who experience clinically significant extravascular hemolysis.

Photo: Marc Dunoyer, CEO of Alexion

The trial met its primary endpoint of change in hemoglobin 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 hemoglobin levels, transfusion avoidance, and FACIT Fatigue scores from baseline.

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.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and severe blood disorder characterized by the destruction of red blood cells, known as intravascular hemolysis (IVH), and white blood cell and platelet activation that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.

Danicopan is an experimental oral medicine in development as an add-on to C5 inhibitor therapy for patients with PNH who experience clinically significant EVH. It is designed to selectively inhibit factor D, a complement system protein that plays a key role in the amplification of the complement system response. Alexion took over development of the drug following its 2019 acquisition of Achillion.

The U.S. Food and Drug Administration granted danicopan Breakthrough Therapy designation the European Medicine Agency granted it PRIority MEdicines (PRIME) status. Danicopan has also been granted Orphan Drug designation in the United States and orphan designation in the European Union  for the treatment of PNH. Alexion is also evaluating danicopan as a potential monotherapy for geographic atrophy in a phase 2 clinical trial.

“These are the first positive phase 3 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,” said Marc Dunoyer, CEO of Alexion.

Author: Rare Daily Staff