Iptacopan for IgAN Meets Phase 2 Trial Primary Endpoint

From June 5-8, 2021, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) held its 58th Annual Congress. Though the event was held virtually, the meeting still expanded an understanding on research and advances within this field. According to a press release, global medicines company Novartis presented data at the Congress. During the presentation, Novartis shared Phase 2 primary endpoint data regarding iptacopan (LNP023), an investigational therapy for patients with IgA nephropathy (IgAN). As IgAN currently has no FDA-approved treatments, this data shows promise for the future of IgAN treatment.


The National Cancer Institute (NCI) describes iptacopan as:

An orally available, small-molecule inhibitor of complement factor B (FB) with potential immunomodulatory activity. Upon administration, iptacopan binds to FB and prevents the formation of the alternative pathway (AP) C3-convertase (C3bBb), [which] limits the cleavage of C3 to the active fragment C3b and may prevent C3b-mediated extravascular hemolysis in certain complement-driven disorders.

So let’s break that down a bit. Complement-driven disorders are those caused by overactivation of the alternative complement pathway. This is part of the immune system. Thus, overactivation leads to inflammation and, ultimately, organ damage. In the case of IgAN, this inflammation affects the kidneys. Learning to treat complement-driven disorders is also important as these conditions affect young adults significantly more than other groups, causing an increased need for dialysis or kidney transplants. For example, up to 30% of patients with IgAN will have kidney failure within 10 years of diagnosis.

By acting as an immunomodulatory agent, iptacopan calms down complement overactivation and inhibits IgAN progression. Beyond IgAN, researchers are also exploring iptacopan as a potential treatment for paroxysmal nocturnal hemoglobinuria (PNH) and membranous nephropathy (MN), among others. Thus far, iptacopan has been granted:

  • Orphan Drug designation. Iptacopan received Orphan Drug designation from the European Medicines Agency (EMA) in regards to IgAN. Additionally, the therapy received Orphan Drug designations from the EMA and FDA for C3 glomerulonephropathy (C3G) and paroxysmal nocturnal hemoglobinuria.
  • PRIME designation. In terms of PRIME designation, iptacopan received this from the EMA for C3G.
  • Breakthrough Therapy designation. Iptacopan was granted Breakthrough Therapy designation from the FDA for the treatment of PNH.

Phase 2 Trial Data

During the Phase 2 clinical trial, researchers evaluated iptacopan for patients with IgAN. Altogether, 112 patients enrolled. Patients received either varying iptacopan doses (up to 200mg 2x daily) or a placebo. Researchers wanted to determine the safety, efficacy, and tolerability of iptacopan. Ultimately, the primary endpoint was a significant proteinuria reduction at 90 days. Prior to the trial, researchers predicted that the highest iptacopan dose would result in a 23% proteinuria reduction. The data shows:

  • Iptacopan reached its primary endpoint within this clinical trial.
  • Altogether, iptacopan was found to be relatively safe and well-tolerated.
  • In addition to reducing proteinuria (excess protein in the urine), iptacopan improved kidney function.

Moving forward, Novartis will continue to evaluate iptacopan in the Phase 3 APPLAUSE clinical trial.

IgA Nephropathy (IgAN)

Also known as Berger’s disease, IgA nephropathy (IgAN) is a chronic kidney disease that damages glomeruli inside the kidneys. Normally, glomeruli help filter excess waste and fluid from the blood. But in patients with IgAN, too much of an antibody called immunoglobulin A (IgA) builds up within the kidneys. IgA usually protects the body from infection. However, over accumulation within the kidneys attacks the glomeruli and causes blood and protein to leak into the urine. Typically, IgAN follows some sort of gastrointestinal or upper respiratory viral infection. In America, males are 2x more likely than females to develop IgAN. The condition is also more common in those of Caucasian or Asian descent.

Symptoms typically appear in teenage years or, at the very least, before age 40. However, many patients may not show symptoms until the condition has progressed. Without early diagnosis and treatment, patients may progress to kidney failure. Please see your doctor if you are displaying symptoms. At the same time, IgAN may also be caught by your doctor via a routine urine test.

Common symptoms include:

  • High blood pressure
  • Proteinuria
  • Foamy or bubbly urine
  • Dark urine
  • Blood in the urine
  • Swelling of the hands and feet
  • Flank pain
  • Low-grade fever
  • Pain in sides of the back below the ribs
  • Drowsiness
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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