A phase 2 clinical trial assessing the safety, efficacy, and pharmacokinetics of iptacopan (LNP023) in autoimmune benign hematological disorders including cold agglutinin disease (CAD) is continuing to recruit participants.

The open-label, multicenter study, which started on December 21, 2021, is recruiting an estimated 30 participants, aged 18 years and older in Germany, Spain, and the UK. Participants will receive 200 mg of iptacopan twice a day for 85 days.

The primary outcome measure for patients with CAD is the ability of the treatment to induce a clinically meaningful increase in hemoglobin levels. Secondary outcome measures include the effect of iptacopan on relevant disease biomarkers such as lactate dehydrogenase, total bilirubin, reticulocytes, and haptoglobin. The number of adverse events and serious adverse events will also be recorded.

Continue Reading

Read more about CAD overview

Iptacopan is an oral investigational therapy by Novartis. It is a first-in-class, potent, and highly selective factor B inhibitor of the alternative complement pathway. It binds to factor B and suppresses the activity of C3 convertase. This way, signaling from the alternative complement pathway and the activation of the amplification loop are also suppressed.

This inhibits the generation of the downstream C5 convertase complex, opsonization, and the formation of C3a and C5a anaphylatoxins and membrane attack complex. Because the direct classical and lectin pathway signaling remains intact, the risk of meningococcal infection is lower with iptacopan compared to terminal complement pathway inhibitors.

CAD is characterized by the overactivation of the complement system and autoimmunity against the body’s own red blood cells in cold temperatures. This leads to anemia due to extravascular hemolysis in the spleen and liver, which is largely complement-dependent through C3 fragments deposition on red blood cells.

So-called complement therapeutics that aim to dampen the overactive complement pathway could, therefore, be a promising therapeutic approach for CAD. The clinical trial is estimated to be completed in November 2025.


Basket study to assess efficacy, safety and PK of iptacopan (LNP023) in autoimmune benign hematological disorders. US National Library of Medicine. Updated February 2, 2022. Accessed February 15, 2022.