Treatment with the factor B inhibitor HSK39297 is more efficacious than eculizumab for the management of paroxysmal nocturnal haemoglobinuria (PNH), with no serious safety concerns, suggests a study presented at EHA 2026.
“HSK39297 demonstrated significantly superior efficacy compared with eculizumab in the treatment of patients with PNH, along with a favourable safety profile,” wrote the authors led by Dr Lina Zhang, Henan Cancer Hospital, Zhengzhou, China.
Seventy-three patients with PNH who have not previously received complement inhibitor therapy were enrolled in this multicentre, randomized, open-label, active-controlled phase III study. Of these, 37 were assigned to the HSK39297 group and 36 in the eculizumab group.
A significantly greater proportion of patients in the HSK39297 than the eculizumab group responded to treatment (59.5 percent, 95 percent confidence interval [CI], 43.2‒75.7 vs 8.3 percent, 95 percent CI, 2.8‒19.4), with an odds ratio of 20.3 (95 percent CI, 4.7‒88.0; p<0.0001) in favour of HSK39297. [EHA 2026, abstract S181]
Likewise, more patients treated with HSK39297 vs eculizumab achieved a ≥2-g/dL increase in haemoglobin from baseline (91.9 percent vs 55.6 percent). The rates for patients not requiring red blood cell (RBC) transfusions were 94.6 percent and 69.4 percent, respectively.
The HSK39297 group demonstrated a significant decrease in lactate dehydrogenase (LDH) and improvements in haemoglobin starting from the first week of treatment.
At weeks 18 to 24, the least squares mean percent change from baseline in LDH was ‒84.0 percent in the HSK39297 group and ‒80.4 percent in the eculizumab group, while the least squares mean changes from baseline in haemoglobin were 5.1 and 2.1 g/dL, respectively.
“HSK39297 demonstrated superiority over eculizumab in terms of the magnitude of haemoglobin improvement, reduction in reticulocyte count, and improvement in FACIT-Fatigue score, without the risk of extravascular haemolysis associated with C3 deposition,” Zhang and colleagues said.
Safety profile
Treatment-emergent adverse events (TEAEs) occurred more frequently in the eculizumab group (86.1 percent vs 75.7 percent). Most TEAEs reported in the HSK39297 group were mild or moderate (grade 1‒2) in severity, with none leading to dose reduction, treatment discontinuation, or study withdrawal.
The most common drug-related TEAE that occurred in at least 5 percent of patients treated with HSK39297 was headache (18.9 percent), followed by lipid disorders (10.8 percent) and bacterial infections (5.4 percent).
In this phase III study, eligible patients with haemoglobin <10 g/dL were stratified based on baseline haemoglobin level (≤7g/dL or >7g/dL) as determined by a central laboratory and history of RBC transfusion within 6 months prior to randomization. Participants were then randomly allocated to receive either HSK39297 200 mg once daily or eculizumab for 24 weeks.
The primary endpoint was the proportion of patients achieving haemoglobin ≥12 g/dL at ≥3 of 4 assessments between weeks 18 and 24, with no RBC transfusions from 2 weeks after treatment initiation. Secondary endpoints were as follows: the proportion of patients achieving a ≥2-g/dL increase in haemoglobin from baseline, the proportion of patients without RBC transfusion, and changes from baseline in haemoglobin, reticulocyte count, LDH, and FACIT-Fatigue score.
“PNH is a rare haematological disorder characterized by intravascular haemolysis, bone marrow failure, and an elevated risk of life-threatening thrombosis,” according to Zhang and colleagues. “HSK39297, an oral complement factor B inhibitor, has been developed … for the treatment of PNH.”