The purpose of this Phase 3 study is to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in study participants with aHUS.

The study is designed as a multicenter, single-arm, open label study to evaluate the efficacy and safety of iptacopan upon switching from anti-C5 antibody to iptacopan treatment in participants with aHUS. It consists of a screening period of up to 14 weeks followed by a 12-Month Core Treatment period and 12-Month Extension Treatment period.

The study will assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS.

Inclusion Criteria:

• Male and female adult participants ≥ 18 years of age with diagnosis of aHUS for whom etiologies of other types of TMA and non-aHUS kidney disease have been excluded.

  •. Currently on the recommended (as per label) dosage regimen of anti-C5 antibody treatment, for at least 3 months prior to entering the screening period.

• In the opinion of the investigator the participant has responded to anti-C5 antibodytreatment prior to screening and has clinical evidence of response (in absence of PE/PI) during the Screening period.

Clinical evidence of response to anti-C5 antibody treatment (in absence of PE/PI) confirmed during the Screening period by central laboratory at two visits 12 weeks apart. Clinical evidence of response is defined as:

1. Hematological normalization in platelet count ≥150 x 10^9/L and LDH below upper limit of normal [ULN], and

2. Stable kidney function as defined by serum creatinine values within ±15% during the Screening period

   • Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required prior to the start of treatment with iptacopan.
   • If not received previously or if a booster is required, vaccination against Haemophilus influenzae infection, should be given, if available and according to local regulations.

Exclusion Criteria:

• History of aHUS disease relapse while on anti-C5 antibody treatment.
• eGFR < 30 ml/min/1.73m^2
• Active infection or history of recurrent invasive infections caused by encapsulated bacteria, i.e., meningococcus, pneumococcus (eg., N. meningitidis, S. pneumoniae) or H. influenzae.
• Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
• Kidney, bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT), heart, lung, small bowel, pancreas, liver transplantation or any other cell or solid organ transplantation
• Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
• Any medical condition deemed likely to interfere with the patient's participation in the study

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com