OBJECTIVES: Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare (1-1.5 per-million), life-threatening disease characterized by complement-mediated hemolysis. Chronic hemolysis-driven anemia can result in persistent fatigue, negatively impacting patients’ quality-of-life (QOL). We report preliminary trends in hemoglobin (Hb) levels and QOL for patients in OPERA, an observational study, presenting the first real-world data on pegcetacoplan (PEG) treatment for US adults with PNH post-approval.

METHODS: The study recruited US patients ≥18 years of age, diagnosed with PNH and prescribed PEG (by a licensed medical professional). OPERA collected information from routine care and did not direct medical interventions. Hemoglobin was reported by site (healthcare provider verified) at baseline (BL), and by patients over 1 year, during monthly follow-up (when available). Hemoglobin analysis only included patients who did not receive a transfusion in the treatment period and reported both a BL and ≥1 follow-up value. Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (0–52 score) and Patient-Reported Outcomes Measurement Information System (PROMIS) scale for Cognitive Abilities (23.27–67.09 t-score) were completed online (low score=negative outcome). Given disease rarity, a small sample size was expected.

RESULTS: Of 44 patients enrolled, 28 qualified (mean age 44 years, 60.7% female, mean [SD] BL Hb of 8.8 [1.7] g/dL). The mean (SD) latest Hb was 11.8 (1.4) g/dL with a median (IQR) follow-up period of 4.0 (2.3) months. Among them, 85.7% reported a Hb change from baseline by ≥1.0 g/dL, 71.4% by ≥2.0 g/dL, and 64.3% achieved Hb normalization (≥12.0 g/dL). For 8 patients with valid QOL data, mean (SD) FACIT-fatigue at BL was 29.4 (12.4) and 37.9 (12.6) at 3 months; mean (SD) PROMIS t-score at BL was 46.1 (9.5) and 50.6 (12.1) at 3 months.

CONCLUSIONS: Thus far, this first real-world study of PEG in US adults with PNH indicates a positive trend in Hb, fatigue, and cognition after treatment.