UK-based biopharmaceutical firm AstraZeneca has unveiled positive results for danicopan, an add-on treatment to Ultomiris (ravulizumab) or Soliris (eculizumab), from Phase 3 ALPHA clinical trial.
Danicopan is an experimental oral medicine intended as an add-on to C5 inhibitor therapy, to selectively inhibit factor D, which plays important role in complement system response.
The drug has been granted Breakthrough Therapy designation from the US Food and Drug Administration, and PRIME status from the European Medicines Agency (EMA).
In addition, danicopan has also secured Orphan Drug Designation in the US, EU and Japan.
ALPHA is a global Phase 3 trial designed to evaluate the efficacy and safety of danicopan as an add-on to C5 inhibitor therapy eculizumab or ravulizumab.
The Phase 3 trial enrolled patients with paroxysmal nocturnal haemoglobinuria (PNH) with clinically significant extravascular haemolysis (EVH).
PNH is a rare, chronic, and potentially life-threatening blood disorder, characterised by red blood cell destruction within blood vessels and white blood cell and platelet activation.
ALPHA trial investigator professor Jong Wook Lee said: “The ALPHA trial demonstrated that adding danicopan to standard of care with eculizumab or ravulizumab significantly improved fatigue and anaemia and reduced transfusion dependence, while still allowing for sustained control of IVH with terminal complement inhibition addressing the thrombotic risks associated with PNH.
“These results suggest danicopan has the potential to be an important option for the small subset of patients with PNH who experience clinically significant EVH while being treated with eculizumab or ravulizumab.”
In the study, danicopan significantly increased the haemoglobin levels and maintained disease control, compared to placebo plus C5 inhibitor therapy.
The add-on treatment showed superior results in patients managing PNH with Ultomiris or Soliris, compared to placebo plus Ultomiris or Soliris
In addition, the drug also showed significant improvements in haemoglobin levels by second week and maintained through 12th week.
The study met all key secondary endpoints of statistical superiority in favour of danicopan plus Ultomiris or Soliris, compared to placebo plus C5 inhibition.
Danicopan is generally well tolerated with no new safety concerns, and no reports of deaths, meningococcal infections, or discontinuations due to haemolysis.
The most common treatment-emergent adverse events (TEAEs) include headache, nausea, arthralgia and diarrhoea in the treatment arm, said the British drugmaker.
Alexion development, regulatory and safety head, senior vice president Gianluca Pirozzi said: “As a leader in PNH for decades, Alexion has transformed the treatment landscape by developing the first approved medicine for this rare disease and establishing C5 complement inhibition as standard of care.
“These promising results presented at the EHA Annual Meeting underscore the potential for targeted Factor D inhibition with danicopan as an add-on to Ultomiris or Soliris to address clinically significant EVH while allowing patients to maintain disease control with established C5 complement inhibitors.”