NEW ORLEANS, La.—A weight-based, 2-tiered crovalimab dosing approach is safe and effective for the treatment of adult and adolescent patients with paroxysmal nocturnal hemoglobinuria (PNH) who are not being treated currently with complement inhibitors, confirmed a new study presented at the 64th ASH Annual Meeting and Exposition.

To characterize the pharmacokinetic profile of crovalimab in healthy volunteers and PNH patients who have not been treated previously, a team of researchers led by Alexandre Sostelly, PhD, MSc, from F. Hoffmann-La Roche Ltd, Basel, Switzerland, analyzed data from 2 clinical trials known as COMPOSER and COMMODORE 3. The researchers also wanted to evaluate the relationship between the exposure parameters of crovalimab and pharmacodynamic biomarkers.

They reported that the crovalimab’s bioavailability was estimated to be 73.8% following subcutaneous administration. The typical half-life of the treatment was 58.7 days. Patients with lower body weight were predicted to experience higher drug exposure, and age was negatively correlated with the absorption rate of the drug. However, this did not have a clinically relevant impact on crovalimab exposure.

The researchers also found that crovalimab induced a concentration-dependent inhibition of terminal complement activity and the concentration of free C5. Crovalimab above 100 μg/mL led to the inhibition of terminal complement activity.

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There was no link between the observed concentration of steady-state crovalimab and lactate dehydrogenase. Increasing the concentration of crovalimab above 100 μg/mL did not result in more lactate dehydrogenase reduction.

Finally, the researchers found no link between crovalimab exposure and the occurrence of adverse events, and no dose adjustments were necessary for other factors such as ethnicity, antidrug antibody status, and hepatic or renal impairment.

Crovalimab is a novel antihuman C5 monoclonal antibody being developed to treat PNH. It can be self-administered subcutaneously, which should be done every 4 weeks.

Reference

Buatois S, Benkali K, Henrich A, Jaminion F, Zhang Y, Sostelly A. Pharmacokinetic characterization and exposure-response relationship of crovalimab in the COMPOSER and COMMODORE 3 trials of patients with paroxysmal nocturnal hemoglobinuria (PNH). 64th ASH Annual Meeting and Exposition. New Orleans, LA; December 10-13, 2022. Poster number 1247.