Efficacy and Safety of Lanoracopan in the Treatment of PNH

In Chinese multicenter phase 3 trials, lanoracopan 400 mg BID was evaluated over 24 weeks. In the active-controlled study (N=66, complement-naïve), the proportion achieving Hb ≥120 g/L was 50.0% (lanoracopan) versus 9.09% (eculizumab). In the single-arm study (N=20, C5 inhibitor-inadequate responders), 70% reached Hb ≥120 g/L, and 100% had Hb increase ≥20 g/L from baseline. No treatment-discontinuation due to AEs, no severe breakthrough hemolysis, no major vascular events, no encapsulated bacterial infections, and no deaths were reported across both studies. These data demonstrate superior hemoglobin correction and favorable short-term safety. However, long-term real-world effectiveness and safety profiles stratified by prior treatment (C5 inhibitors vs. other factor B inhibitors) remain uncharacterized. This observational study will enroll a diverse cohort to capture durability of Hb response, transfusion independence rate, incidence of breakthrough hemolysis and thrombosis, and adverse event patterns over extended follow-up, providing evidence to guide therapy switching and sequencing in clinical practice.

Inclusion criteria

• Age 18-75 years.
• Diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) meeting any of the following conditions:

• Newly diagnosed PNH with active hemolysis (hemoglobin [Hb] <100 g/L, lactate dehydrogenase [LDH] >1.5×upper limit of normal [ULN]);
• Receiving a stable regimen of complement C5 monoclonal antibody (eculizumab) at standard dose and interval for ≥3 months, with Hb still <120 g/L despite treatment;
• Intolerant to eculizumab therapy;
• Receiving standard iptacopan therapy for ≥3 months, with Hb still <120 g/L;
• Intolerant to iptacopan therapy.
• Currently receiving standard lanoracopan therapy (patients who have completed lanoracopan clinical trials).
• Vaccination against meningococcal infection (quadrivalent conjugate vaccine, MenACWY) is required prior to the first dose of study drug (Day 1). If not vaccinated within 3 years prior to Day 1, vaccination must be administered at least 14 days before Day 1; if administered within 14 days before Day 1, antibiotic prophylaxis against meningococcal infection is required until 14 days post-vaccination.
• Vaccination against pneumococcal infection is required prior to Day 1. If not vaccinated within 5 years prior to Day 1, vaccination must be administered at least 14 days before Day 1; if administered within 14 days before Day 1, antibiotic prophylaxis against pneumococcal infection is required until 14 days post-vaccination.
• Willing and able to provide written informed consent and comply with study procedures.

Exclusion criteria

• Previous bone marrow or hematopoietic stem cell transplantation.
• Previous splenectomy.
• Known or suspected hereditary complement deficiency.
• History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus.
• A history of malignancy within 5 years before screening, except cured local basal cell carcinoma of the skin and carcinoma in situ of the cervix.
• Severe concurrent illness, including severe renal disease (e.g., dialysis), advanced cardiac disease (NYHA class IV), severe pulmonary hypertension (WHO class IV), or unstable thrombotic events, judged unsuitable for participation by the investigator.
• Any other condition that, in the investigator's opinion, may interfere with study conduct, increase subject risk, or preclude safe participation and completion, including concomitant disease, treatment, procedure, surgery, or clinically significant laboratory abnormality.
• Pregnant or breastfeeding women.