NEW ORLEANS, La.—Switching from high-dose intravenous eculizumab to standard, weight-based intravenous ravulizumab seems to be well-tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH), and leads to minimal changes in laboratory measures associated with disease symptoms.

These findings, which were presented at the 64th ASH Annual Meeting and Exposition, are based on the interim analysis of data from 10 patients with the disease.

Some patients who are treated with the approved, fixed dose of eculizumab (900 mg once every 2 weeks) experience insufficient intravascular hemolysis inhibition and need to have their eculizumab dose increased, which can lead to side effects.

To assess the safety of switching from high-dose eculizumab (1200 mg once every 2 weeks) to ravulizumab once every 8 weeks based on weight, a phase 4, single-arm clinical trial was initiated. (Ravulizumab is a second‑generation analog of eculizumab but with longer dosing intervals).

Read more about the prognosis of PNH

Eighteen patients were already enrolled in the trial. Data from 10 patients showed that up to day 183 from the switch, no free C5‑associated breakthrough hemolysis occurred in any of the 10. Moreover, the concentration of free C5 remained below 0.5 μg/mL for all patients. The safety profile of ravulizumab was comparable with previous studies, and there were no meningococcal infections or treatment-emergent serious adverse events.

Eculizumab is a humanized monoclonal immunoglobulin G antibody against complement C5. It works by inhibiting the cleavage of C5 into C5a and C5b, thereby inhibiting the deployment of the terminal complement system and hemolysis. Ravulizumab has substitutions of 4 amino acids in its chemical backbone. Both eculizumab and ravulizumab are the current standards of care in patients with PNH, a disease characterized by terminal complement activation, intravascular hemolysis, thrombotic events, and organ damage.

References

Griffin M, Gandhi S, Hicks E, et al. Terminal complement inhibition and control of hemolysis in paroxysmal nocturnal hemoglobinuria following switching from high-dose eculizumab to ravulizumab: an interim analysis. 64th ASH Annual Meeting and Exposition. New Orleans, LA; December 10-13, 2022. Poster number 1251.

Ravulizumab in adult participants with paroxysmal nocturnal hemoglobinuria currently treated with high-dose eculizumab. ClinicalTrials.gov. Last updated September 2, 2022. Accessed November 23, 2022.