Pegcetacoplan Demonstrates Control in Both C5i-Experienced and Naïve PNH

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Pegcetacoplan (Empaveli; Sobi and Apellis) demonstrated improved disease measures in patients with paroxysmal nocturnal hemoglobinuria (PNH) both experienced (Ce) and naïve (Cn) to complement 5 inhibitors (C5i) in real-world data.¹

These findings, from a real-world cross-sectional study, were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California, by Koo Wilson, MSc, Swedish Orphan Biovitrum AB, Stockholm, Sweden.

“Current treatments include inhibitors that target terminal C5i or proximal complement, e.g., complement 3, factor B or factor D. Pegcetacoplan, an inhibitor of complement components C3 and C3b, was approved by the European Medicines Agency in 2021 as a second line treatment exclusively,” Wilson and colleagues wrote.¹ “A recent expansion to the indication by the EMA has made pegcetacoplan available for the treatment of all adults with PNH who have hemolytic anemia, based on the PEGASUS² and PRINCE study results which show improvements in both hemoglobin (Hb) and lactate dehydrogenase (LDH), regardless of previous C5i treatment experience.”

The study included patients with PNH from the Adelphi PNH II Disease Specific Programme in Canada, France, Germany, Italy, Spain, and the UK, with data collected between December 2023 and April 2024. There were 63 participants (Ce, 52; Cn, 11) included whose data were reported by 53 physicians, and who were prescribed pegcetacoplan for at least 3 months prior to study inclusion. Ce participants had a mean age of 49.4 years (standard deviation [SD], 15.8]) and were 63.5% male whereas Cn participants had a mean age of 32.1 (SD, 7.4) and were 48.4% male. Around half (48.1%) of Ce participants had a diagnosed concomitant condition as compared to 27.3% of Cn participants. These participants had a median of 3.1 years (IQR, 2.0-5.5) and 1.3 years (IQR, 0.8-3.7) since PNH diagnosis and a median 0.6 years (IQR, 0.4-0.9) and 0.7 years (IQR, 0.5-1.12) since pegcetacoplan initiation, respectively.¹

Complete adherence to treatment was reported for 86.5% of Ce and 90.9% of Cn participants. Wilson and colleagues found that mean Hb levels increased from 8.8 g/dL (SD, 1.1) to 11.3 g/dL (SD, 1.7) in 50 evaluable Ce participants and from 7.4 g/dL (SD, 1.9) to 11.7 g/dL (SD, 1.3) in 10 evaluable Cn participants. Mean LDH levels decreased from 503.6 U/L (SD, 268.5) to 292.5 U/L (SD, 140.2) in 51 evaluable Ce participants and from 977.8 U/L (SD, 713.4) to 358.9 U/L (SD, 237.4) in 9 evaluable Cn participants. Mean absolute reticulocyte count decreased from 92.4 x10⁹/L (SD, 28.2) to 77.5 x10⁹/L (SD, 28.9) in 35 evaluable participants and increased from 58.8 x10⁹/L (SD, 24.4) to 61.7 x10⁹/L (SD, 29.4) in 6 evaluable Cn participants.¹

Investigators also found that moderate or severe fatigue was reported for 76.9% of Ce patients at pegcetacoplan initiation and 21.1% at data collection, along with 72.7% of Cn patients at pegcetacoplan initiation and 9.1% at data collection. Twenty patients (Ce,12; Cn, 8) also provided Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at the time of data collection with mean scores of 40.1 (SD, 9.3) and 34.6 (SD, 13.5) for the Ce and Cn group, respectively.¹

Prior to pegcetacoplan initiation, physicians reported a mean 3.4 annual transfusions (SD, 2.9) and 3.8 infusions in the Ce and Cn groups, respectively. Of the 29 Ce and 8 Cn participants prescribed pegcetacoplan for at least 6 months, 28% of the Ce group and 11% of the Cn group required a transfusion within the 6 months prior to data collection. At the survey time, 96.2% of the Ce group and 100% of the Cn group (increases from 15.4% and 9.1%, respectively) were described by physicians to have their PNH controlled “well/very well”. Notably, this real-world clinical experience study did not report safety data.¹

“These real-world data suggest that complement-inhibitor naïve patients may experience similar outcomes to those who had previously been prescribed C5i, following pegcetacoplan initiation, and are consistent with evidence reported from clinical trials such as improvements in Hb and LDH regardless of prior complement treatment,” Wilson and colleagues wrote.¹ “These findings encourage the possibility of pegcetacoplan as an efficacious therapy for both complement inhibitor-experienced and naïve PNH patients in real-world experience.”

REFERENCES

1. Panse J, Llamas JCV, Wilson K, et al. Real-World Clinical Outcomes for Complement Inhibitor Experienced and Naïve Paroxysmal Nocturnal Hemoglobinuria Patients Prescribed Pegcetacoplan in Europe and Canada. Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 5085.

2. Hillmen P, Szer J, Weitz I, et al. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Eng J Med. 2021;384(11):1028-1037. doi: 10.1056/NEJMoa2029073