Experimental AAV treatment reduces kidney damage in animal models
Study data support izicopan's potential in AAV, other kidney diseases
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Izicopan, InflaRx’s experimental oral therapy for ANCA-associated vasculitis (AAV), was shown to reduce kidney damage in two different animal models of kidney injury.
That’s according to data presented in a poster at the American Society of Nephrology’s Kidney Week 2026, held Oct. 21-25 in Denver. The poster was titled “Izicopan, a second-generation oral C5a receptor 1 (C5aR1) antagonist, demonstrates promising therapeutic potential in kidney disease models.”
“The pre-clinical data presented at Kidney Week demonstrate the ability of izicopan to attenuate [kidney] injury and provide a strong rationale for further development in [kidney] diseases,” Renfeng Guo, MD, chief scientific officer and founder of InflaRx and a coauthor of the poster, said in a company press release. “Combined with its differentiated [pharmacological] profile, including potentially reduced drug-drug interaction liability, faster onset of action, and more convenient dosing, we believe these results further support izicopan’s best-in-class potential.”
Izicopan designed to block key proteins
AAV is an autoimmune disorder marked by inflammation in small blood vessels. This can damage organs, especially the kidneys, which are full of tiny blood vessels and are responsible for filtering blood.
Most cases are caused by self-reactive antibodies, called ANCAs, against proteins produced by immune cells called neutrophils. This results in the cells’ overactivation and inflammatory damage in neighboring blood vessels.
A group of immune proteins known as the complement cascade plays a key role in AAV-driving inflammation. In particular, the complement protein C5a can bind to receptor proteins, called C5aRs, on neutrophils, boosting the production of ANCA target proteins and amplifying the autoimmune responses that fuel the disease.
Izicopan is designed to block C5aR proteins, with the goal of preventing their binding with C5a, reducing inflammation, and ultimately lessening disease activity. The therapy’s mechanism of action is similar to that of Tavneos (avacopan), an oral therapy sold by Amgen.
In the U.S., Tavneos is currently approved for the most common types of AAV, though U.S. regulators are considering revoking the therapy’s approval following allegations of data manipulation in the trials that formed the basis of approval. These revelations led to Tavneos being pulled from the market in the European Union in August, and the AAV community in the U.K. is bracing for a similar withdrawal.
Therapy faster than Tavenos at reaching therapeutic levels
In the poster, the researchers presented data supporting izicopan’s differentiated pharmacological profile. Compared with Tavneos, the experimental therapy “preserves the structural features” needed for a strong binding to C5aR, but is faster at reaching therapeutic levels (days versus weeks), according to InflaRx.
Importantly, izicopan is less likely to interact with CYP3A4/5, a molecule key for the metabolism of several drugs, including glucocorticoids, a standard AAV treatment. This reduces the chances of drug-drug interactions. The therapy candidate also seems to have a more favorable metabolic profile and lower risk of liver toxicity.
Newly presented data also concerned experiments in which izicopan was tested in two hamster models of kidney injury. In both of these models, the animals basically undergo a surgery that triggers physical damage within the kidney. Although this surgery-induced injury is different from what happens in AAV, the resulting damage also leads to complement activation.
Izicopan demonstrated robust [suppression] of C5aR-mediated inflammatory responses and [kidney] protection, supporting it as a therapeutic candidate for complement-driven kidney diseases.
In both models, animals treated with izicopan (either before surgery or before surgery and after surgery) showed significant reductions in blood markers associated with kidney injury. Consistently, analyses of the hamsters’ kidney tissues indicated that those treated with izicopan had less damage and cell death.
“Izicopan demonstrated robust [suppression] of C5aR-mediated inflammatory responses and [kidney] protection, supporting it as a therapeutic candidate for complement-driven kidney diseases,” the researchers wrote in the poster.
InflaRx is currently making preparations for a Phase 2 clinical trial to test izicopan in people with AAV. The therapy has already shown an acceptable safety profile and promising signs of biological activity in prior trials of healthy volunteers or people with complement-related skin conditions.
According to the company, the newly presented data support the potential for izicopan in AAV and other kidney disorders.
“There is an important need for effective, safer treatment options for patients with complement-mediated inflammatory diseases, particularly in [kidney] indications,” Guo said. “We are excited to be advancing oral izicopan in ANCA-associated vasculitis as well as in additional kidney diseases.”
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