Iptacopan at a dose of 200 mg twice a day is optimal to provide maximal disease control in paroxysmal nocturnal hemoglobinuria (PNH), according to a new dose-exposure-response analysis presented at the 64th ASH Annual Meeting and Exposition.

The dose-exposure-response relationship was comparable among patients regardless of whether they had a partial response to C5 inhibition or were anti-C5-naïve. This finding, the researchers said, supports the use of iptacopan at this dose in both patient populations.

Previous research has shown that iptacopan can provide hematologic benefits in patients with PNH who had active hemolysis.

To evaluate the dose-exposure-response relationships of biomarkers and efficacy measures to support dose selection for iptacopan, a team of researchers led by Jun Ho Jang, MD, PhD, from Sungkyunkwan University School of Medicine and Samsung Medical Center in Seoul, Korea, analyzed data from 2 open-label phase 2 clinical trials testing the safety, efficacy, pharmacokinetics, and pharmacodynamics of iptacopan in adults with PNH. 

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The 2 trials enrolled 29 patients. Of these, 16 had active hemolysis despite treatment with anti-C5 therapy (enrolled in the first trial) and 13 had active hemolysis but no prior anti‑C5 therapy (enrolled in the second trial).

The pharmacokinetic parameters of the treatment were similar in the 2 trials and were in line with previous reports.

An increase in dose in the 25 to 200 mg twice a day range resulted in a less than proportional increase in exposure. Exposure was not significantly impacted by the age and sex of the patients. 

The researchers identified a dose of 200 mg twice a day as the optimum regimen to achieve a Ctrough of more than 750 ng/mL and hence provide maximal disease control in most patients.

Based on these findings, 2 ongoing phase 3 clinical trials are now investigating 200 mg twice-daily iptacopan in anti-C5-treated and anti-C5-naïve patients with PNH.

Iptacopan is an investigational oral, selective, reversible complement factor B inhibitor of the alternative complement pathway. 


Risitano AM, De Latour RP, Yap ES, et al. Dose-exposure-response relationships of biomarkers and efficacy measures with iptacopan, a complement factor B inhibitor, in patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH) with or without concomitant anti-C5 therapy. 64th ASH Annual Meeting and Exposition. New Orleans, LA, December 10-13, 2022. Poster number 2571.