Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)

Summary

The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.

Timeline

Start

2020-12-16

Primary completion

2022-06-29

Completion

2024-01-16

Outcome

Met primary endpoint

registry analysis (superiority test); Danicopan (TP1) vs Placebo (TP1); p <0.0001; LS Mean Difference 24.44 (95% CI 16.90 to 31.99); Mixed Models Analysis NCT04469465 ↗

paper The primary end point was met, with Hb improvements from baseline at week 12 (least squares mean change, 2.8 g/dL) with danicopan. PMID 39700502 ↗

release “Results from ALPHA Phase III trial demonstrated statistically significant increase compared to placebo in mean haemoglobin from baseline to week 12” astrazeneca.com ↗

release “The trial met its primary endpoint of change in haemoglobin from baseline at 12 weeks” astrazeneca.com ↗

Publications

• Results Lee JW, Griffin M, Kim JS, Lee Lee LW, Piatek C, Nishimura JI, Carrillo Infante C, Jain D, Liu P, Filippov G, Sicre de Fontbrune F, Risitano A, Kulasekararaj AG; ALXN2040-PNH-301 Investigators. Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. Lancet Haematol. 2023 Dec;10(12):e955-e965. doi: 10.1016/S2352-3026(23)00315-0.
• Kulasekararaj A, Griffin M, Piatek C, Shammo J, Nishimura JI, Patriquin C, Schrezenmeier H, Barcellini W, Panse J, Gaya A, Patel Y, Liu P, Filippov G, Sicre de Fontbrune F, Risitano A, Lee JW. Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH. Blood. 2025 Feb 20;145(8):811-822. doi: 10.1182/blood.2024026299.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Danicopan	Small molecule	150 mg	Oral
Background	Eculizumab	Monoclonal antibody	—	—
Background	Ravulizumab	Monoclonal antibody	—	—

Indications