Oral vasculitis treatment safe, shows promise in healthy volunteers in study

Izicopan, Inflarx’s experimental oral treatment for ANCA-associated vasculitis (AAV), was safe and showed promise for treating the autoimmune disease in a first-in-human trial involving healthy volunteers.

That’s according to newly published data from the early clinical trial, which enrolled more than 80 healthy adults. Company researchers noted that the treatment candidate was well tolerated and  showed promising pharmacological activity at multiple doses.

“Izicopan demonstrated rapid and sustained [suppression of its target signaling], favorable [pharmacological] properties and a strong safety and tolerability profile across the doses evaluated,” Niels C. Riedemann, MD, PhD, founder and CEO of Inflarx, said in a company press release, which further stated that the results “support Phase 2 development of izicopan in immune-inflammatory diseases.”

Inflarx is now gearing up for a pair of Phase 2 clinical trials to test izicopan in people with AAV. One study will test the drug candidate against a placebo in AAV patients with kidney involvement, while the other will assess izicopan’s ability to replace standard corticosteroids in a wider range of people with AAV who have newly diagnosed disease. Both studies are expected to launch next year.

According to Riedemann, the findings to date “provide a solid clinical pharmacology foundation for our Phase 2 programs.”

The results from the Phase 1 testing in healthy volunteers were detailed in “A First-In-Human, Randomized, Placebo-Controlled Single and Multiple Ascending Dose Study of Izicopan (INF904), A Second-Generation Oral Small Molecule C5a Receptor Inhibitor, in Healthy Participants,” a study published in the journal Clinical Pharmacology in Drug Development. The work was funded by Inflarx and all 13 authors work for Inflarx companies.

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AAV is marked by inflammation in small blood vessels, which can damage organs such as the kidneys and lungs. As part of this inflammation, a molecule called C5a is produced, which binds to the C5aR1 receptor on the surface of immune cells to help drive blood vessel damage.

Izicopan is designed to block that receptor protein, thereby limiting this damage. Inflarx is developing the oral therapy with the goal of offering a safer and more convenient alternative to Tavneos (avacopan), a twice-daily oral therapy from Amgen also designed to block C5aR1.

Tavneos is approved in the U.S. to treat patients with certain types of AAV, though that approval has come under scrutiny due to allegations of data manipulation in clinical trials. In Europe, approval of Tavneos has already been revoked.

Izicopan previously eased kidney damage in rodent models in lab

In preclinical studies, izicopan was shown to ease kidney damage in rodent models of kidney injury.

The Phase 1 trial evaluated the safety profile and pharmacological activity of increasing doses of izicopan in 86 healthy volunteers. In the first part, participants were randomly assigned to receive either a single dose of izicopan — 3 mg to 240 mg — or a placebo. Then, in the second part, participants were randomly assigned to take izicopan at doses of either 30 mg once daily, 30 mg twice daily, or 90 mg twice daily, for two weeks.

Safety data were overall positive: None of the participants discontinued the study, and no serious safety problems or clinically relevant changes in lab tests were documented.

“In this first-in-human Phase 1 study in healthy participants, izicopan was associated with only mild or moderate AEs [adverse events] and no serious AEs or discontinuations due to AEs, across all single and multiple doses evaluated,” the researchers wrote.

These encouraging findings will enable further development of izicopan in Phase 2 patient studies.

Pharmacological data indicated that the therapy was working as designed. When C5a binds to C5aR1 on immune cells, the cells increase production of a protein called CD11b in response. Data showed that, in patients taking izicopan twice daily, this effect was reduced by upward of 90%.

“Sufficient izicopan exposure was achieved rapidly within 2 days following [twice-daily] dosing to achieve [more than] 90% blockade of C5a-C5aR1 signaling,” the researchers wrote. “These encouraging findings will enable further development of izicopan in Phase 2 patient studies that will examine the safety, [pharmacological] profile, and efficacy potential of this molecule over longer durations.”