Long-term efficacy and safety of iptacopan in PNH with anaemia

Iptacopan showed sustained efficacy and safety in participants with paroxysmal nocturnal haemoglobinuria (PNH) and persistent anaemia who had already received anti-C5 therapy. The results of the final analysis of the phase 3 APPLY-PNH trial are potentially practice-changing in the field of PNH.

“Up to 82% of patients with PNH treated with anti-C5 have persistent anaemia, mostly due to extravascular haemolysis [1],” explained speaker Prof. Antonio Risitano (University of Naples, Italy). To overcome this issue, iptacopan, targeting factor B proximally in the alternative complement pathway, was tested in the APPLY-PNH trial (NCT04558918; n=97) [2]. Previous results showed that iptacopan monotherapy was superior to eculizumab/ravulizumab concerning various efficacy endpoints already after 24 weeks. Based on these results, participants in the anti-C5 therapy arm (n=35) switched to iptacopan (switch arm), whereas those already on iptacopan remained on this therapy. Prof. Risitano presented the 48-week findings of the APPLY-PNH trial [3].

Improvements in haemoglobin levels were maintained in the iptacopan arm and participants who switched from anti-C5 to iptacopan (switch arm) displayed swift increases in haemoglobin levels (see Figure). Haemoglobin changes from baseline to week 47 were +3.35 g/dL and +3.36 g/dL in the iptacopan and switch arms, respectively. “Over 90% of participants in both iptacopan treatment arms did not require red blood cell transfusions after 2 weeks of iptacopan therapy,” expressed Prof. Risitano. Participant-reported fatigue, as measured by the FACIT-Fatigue score, was also improved at week 48, with changes from baseline of approximately +10 points in both iptacopan study arms. Breakthrough haemolysis events were uncommon in participants treated with iptacopan with rates of 3.2% and 8.2% in the first 24 weeks and final 24 weeks of the study in the iptacopan arm, and rates of 17.1% and 2.9% before and after the switch to iptacopan in the switch arm.

Figure: Mean haemoglobin levels increase upon iptacopan switch over the course of the APPLY-PNH study [3]



The safety profile of iptacopan monotherapy after 48 weeks was consistent with the favourable 24-week data. No serious infections, cases of treatment-emergent haemolysis, discontinuations due to treatment-related adverse events, or deaths were reported.

“This long-term data shows a durable response to iptacopan monotherapy with comprehensive control of intravascular and extravascular haemolysis,” concluded Prof. Risitano.

1. Risitano AM, et al. Front Immunol.2019;10:1157
2. Peffault de Latour R, et al. Blood 2022;140(Suppl 2):LBA-2
3. Risitano AM, et al. Factor B inhibition with oral iptacopan mono therapy demonstrates sustained long-term efficacy and safety in anti-C5-treated patients with paroxysmal nocturnal hemoglobinuria and persistent anemia: final 48-week results from the multicenter, phase III APPLY-PNH trial. Abstract 571, 65^th ASH Annual Meeting, 9–12 December 2023, San Diego, CA, USA.

 

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Posted on 7 February, 20247 February, 2024