Associate Professor, Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California

Caroline Piatek, MD

Piatek shared the latest data update from the phase 3 ALPHA study at the ASH 2024.

Caroline Piatek, MD: Improving Patient-Reported Outcomes in PNH With Danicopan Add-on Therapy

Long-term danicopan add-on therapy to ravulizumab or eculizumab in people with paroxysmal nocturnal hemoglobinuria (PNH) and clinically significant extravascular hemolysis (csEVH) resulted in sustained improvements in patient-reported fatigue, QoL and physical function.

These findings are from long-term follow-up data for up to 72 weeks in the phase 3 ALPHA study and were presented at the

 66th American Society of Hematology (ASH) Annual Meeting and Exposition

, held December 7-10, 2024, in San Diego, California, by Caroline Piatek, MD, Associate Professor, Jane Anne Nohl Division of Hematology, Keck School of Medicine, University of Southern California.

“One of the issues with PNH is that patients report a lot of fatigue, and so having medications that can improve that symptom for the patients is clinically meaningful,” Piatek told 

The ALPHA study is a double-blind, placebo-controlled clinical trial that randomized adult patients with PNH, csEVH, and at least 6 months’ treatment with ravulizumab or eculizumab to danicopan (n = 57) or placebo (n = 29). Of all participants, 54 and 26, respectively, completed the study up to week 24; and 46 and 24 patients, respectively, completed the long-term extension.

Piatek and colleagues found that at week 12, change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score was significantly greater for patients receiving danicopan compared with those receiving placebo in the double-blinded phase (least-squares mean, 8.13 [95% CI, 6.30-9.96] vs 2.53 [95% CI, −0.22-4.91], respectively; 

= .0004). European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) fatigue subscale scores in the danicopan arm improved from a mean 43.3 (standard deviation [SD], 27.2) at baseline to 27.4 (SD, 20.3), 25.4 (SD, 23.6), and 27.8 (SD, 22.2) at weeks 12, 24, and 72, comparable with the general population norm (29.5); whereas in the placebo–danicopan arm scores improved from 49.0 (SD, 25.8) at baseline to 47.1 (SD, 28.6), 37.5 (SD. 27.8), and 44.9 (SD, 24.2), respectively.Mean EQ-5D-3L scores largely remained stable.

Piatek C, Lee JW, Griffin N, et al. Danicopan As Add-on Therapy to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-Term Patient-Reported Outcomes from the Phase 3 ALPHA Trial. Presented at: Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 2692.

Caroline Piatek, MD

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