Paroxysmal nocturnal hemoglobinuria: 2026 so far

Attention moved from lab hemolysis control to ongoing anemia.

In January 2026 to September 2026, newer proximal approaches (treatments that block complement earlier in the pathway) were often discussed as a way to address anemia and transfusion needs that can persist on C5 inhibitors. This included factor B inhibition (blocking a complement protein called factor B) with oral iptacopan. A 24-week switch study reported a hemoglobin rise and improved fatigue and treatment satisfaction after switching from stable anti-C5 therapy to iptacopan monotherapy, with no breakthrough hemolysis or major vascular events reported during that study period. Smaller reports (single cases and a three-person series) also described higher hemoglobin and reduced transfusion needs after switching to iptacopan, but these reports are limited in size and how well they apply to everyone. In these reports, a recurring reason for exploring proximal and oral targets was ongoing anemia and fatigue even when LDH (a blood marker often used to track hemolysis) was controlled.

Research covered in: January 2026, February 2026, March 2026, June 2026

Routine-care data added stability, access burdens, and safety context.

From January 2026 to September 2026, several real-world datasets suggested that ravulizumab use (including switching from eculizumab) was generally linked with maintained biochemical hemolysis control and reduced transfusion needs in routine care. One cohort also reported a preference for the convenience. At the same time, real-world reports described burdens and differences in access, including delays, travel, and repeated visits. They also showed how spontaneous safety reporting (pharmacovigilance, a system that collects side effect reports after a drug is in use) can capture early post-start patterns, including reports of Neisseria meningitidis infection. Registry follow-up also described near-normal LDH and common transfusion independence after at least 6 months of ravulizumab, while emphasizing that these sources describe what happened in practice rather than proving head-to-head superiority. Overall, C5 blockade was repeatedly presented as a foundation for hemolysis control, but the treatment experience in real life also included logistics and ongoing safety monitoring.

Research covered in: January 2026, March 2026, April 2026

More pooled and indirect comparisons, limited direct head-to-head clarity.

So far in 2026, evidence for pegcetacoplan and crovalimab increased mainly through meta-analyses (studies that combine results from multiple studies), subgroup analyses (looking at a subset of trial participants), and indirect cross-trial comparisons rather than direct head-to-head trials. A randomized trial subgroup analysis in complement inhibitor-naive Chinese adults reported crovalimab and eculizumab were very similar on key blood outcomes over 24 weeks, with greater fatigue improvement reported with crovalimab in that analysis. For pegcetacoplan, a meta-analysis and a Spanish routine-care cohort both reported higher hemoglobin and fewer transfusions after switching from prior therapy. An indirect comparison across trials estimated pegcetacoplan outperformed crovalimab on transfusion avoidance and hemoglobin stabilization, but this was an estimate rather than a within-trial comparison. In the months covered, these non-C5 options were often linked with better anemia and transfusion outcomes in selected settings, while the best choice between them remained uncertain because many comparisons were indirect.

Research covered in: April 2026, June 2026, August 2026

Patient-reported burden became more central than single lab targets.

Surveys and observational studies published in the months covered often described a gap between improved hemolysis markers and ongoing symptoms, especially fatigue and low hemoglobin, among people on long-term C5 inhibitors. An observational snapshot of adults already using complement inhibitors found quality of life tracked strongly with hemoglobin level (worse under 10 g/dL). In that study, a lab definition of residual intravascular hemolysis (LDH-based) did not separate quality-of-life scores in the same way, and fatigue remained prominent even after accounting for hemoglobin. A Turkish multicenter study of adults receiving eculizumab reported that 37.5% met a study definition of severe fatigue. A US mixed-methods study (combining interviews and measured data) quantified treatment-day time burden, reporting a median of 3 hours 15 minutes per administration for parenteral complement inhibitors (treatments given by infusion or injection). Taken together, these reports repeatedly described symptom burden and time and logistics costs as major parts of living with treated PNH in January 2026 to September 2026.

Research covered in: February 2026, June 2026, August 2026, September 2026

Real-world practice variation and switch-period vulnerability became clearer.

In January 2026 to September 2026, observational cohorts and center surveys reinforced that thrombosis (blood clots) still occurred in PNH, with reported rates and risk patterns varying by setting and treatment access. A survey of Italian centers found wide variation in preventive anticoagulation (blood thinners used to prevent clots) before starting complement inhibitors. It also reported universal anticoagulation after a clot, and frequent indefinite continuation even alongside complement inhibition. A multicenter real-world switching report found hemolytic events within 14 days were reported more often when switching from a proximal inhibitor to a terminal inhibitor (13 of 29 switches, 44%), though no thrombosis or deaths were reported during switching in that dataset. In these reports, clot-prevention choices and treatment transitions were presented as areas where practice differs, and where short-term instability can occur even when severe outcomes were not seen in the reported switch cohort.

Research covered in: June 2026, July 2026, September 2026