Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy

Main Inclusion Criteria:

• Adult patients with evidence of active thrombotic microangiopathy (TMA), includingthrombocytopenia, evidence of hemolysis, and acute kidney injury

• Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae andHaemophilus influenzae infections are required prior to the start of studytreatment. If the patient has not been previously vaccinated, or if a booster isrequired, vaccine should be given according to local regulations, at least 2 weeksprior to first study drug administration. If study treatment has to start earlierthan 2 weeks post vaccination or before vaccination is given, prophylacticantibiotic treatment must be administered at the start of study treatment and for atleast 2 weeks after vaccination

Main Exclusion Criteria:

• Treatment with complement inhibitors, including anti-C5 antibody

• ADAMTS13 deficiency (<10% activity or <0.1U/ml), and/or Shiga toxin-relatedhemolytic uremic syndrome (STx-HUS), and/or Positive direct Coombs test

• Identified drug exposure-related HUS or HUS related to known genetic defects ofcobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS

• Receiving PE/PI, for 14 days or longer, prior to the start of screening for thecurrent TMA

• Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT),heart, lung, small bowel, pancreas, or liver transplantation

• Patients with sepsis or active severe systemic bacterial, viral (including COVID-19)or fungal infection, systemic infection which confounds an accurate diagnosis ofaHUS or impedes the ability to manage the aHUS disease, active infection (or historyof recurrent invasive infections) caused by encapsulated bacteria

• Kidney disease suggestive of other disease than aHUS or of chronic kidney failure orfamily history of non-complement mediated genetic kidney disease

• Liver disease or liver injury at screening

• Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), orantiphospholipid antibody positivity or syndrome

• Chronic hemo- or peritoneal dialysis

Other protocol-defined inclusion/exclusion criteria may apply