In wake of Tavneos setback, developer working on 2 new vasculitis treaments
Inflarx exploring EU approval pathways for AAV drugs now in trials
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Following regulatory attempts in Europe to revoke approval of its ANCA-associated vasculitis (AAV) therapy Tavneos (avacopan), developer Inflarx is now looking to advance two new treatments — both being tested in clinical trials — for this group of autoimmune diseases.
The biopharmaceutical company said in a press release that it plans to discuss, with the European Medicines Agency (EMA), potential approval pathways for its experimental treatments vilobelimab and izicopan. According to Inflarx, these anti-inflammatory medications provide complementary approaches addressing the “significant unmet medical need in AAV.”
This move follows the recent recommendation from the EMA’s Committee for Medicinal Products for Human Use (CHMP) to revoke Tavneos’ approval in the European Union. The CHMP’s recommendation came after the body concluded that available data in the medication’s regulatory application did not adequately demonstrate its effectiveness. A final decision on Tavneos will be made by the European Commission, which issues final drug marketing authorizations in the EU.
Meanwhile, Inflarx says it’s “assessing the feasibility of broadening its development and registrational strategy for AAV in Europe,” with a focus on vilobelimab and izicopan.
“Recent developments in the ANCA-associated vasculitis treatment landscape reinforce both the seriousness of this disease and the importance of therapies with a strong mechanistic rationale, robust clinical evidence and a differentiated benefit-risk profile,” said Niels C. Riedemann, Inflarx’s founder and CEO.
According to the company, a previously announced Phase 2 trial testing izicopan remains on schedule. Inflarx believes vilobelimab is ready to enter a Phase 3 clinical trial after completing two Phase 2 studies in the U.S. and Europe.
These treatments are part of the company’s broader strategy to inhibit the complement pathway, a part of the immune system involved in AAV damage.
AAV is caused by the immune system mistakenly attacking small blood vessels, causing inflammation and organ damage. It is typically driven by self-reactive antibodies called ANCAs that overactivate neutrophils, a type of immune cell, leading to activation of the complement pathway. This triggers the production of the complement protein C5a, which engages receptors on neutrophils, further enhancing their aberrant activation.
Izicopan shows potential for once-daily dosing, per developer
Izicopan is a small oral molecule that selectively binds to the C5a receptor (C5aR), blocking its interaction with C5a. By inhibiting C5aR signaling, izicopan can reduce neutrophil activation, inflammation, and subsequent damage to small blood vessels.
Results from a first-in-human Phase 1 trial demonstrated that izicopan was well tolerated in healthy volunteers and led to significantly higher drug exposure in the body and C5aR blockade than that reported for Tavneos. The embattled therapy was approved as an add-on treatment for adults with severe and active granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), the most common types of AAV.
Moreover, according to Inflarx, izicopan also showed potential for once-daily dosing.
The planned Phase 2 trial will randomly assign AAV patients to receive either izicopan or a placebo twice daily, alongside rituximab and a tapering course of glucocorticoids. Treatment will be given for six months to induce disease remission. Rituximab (marketed as Rituxan, among others) is approved for the treatment of MPA and GPA.
Trial participants will then continue their assigned treatment with rituximab for another six months as maintenance therapy, with some in the izicopan group switching to once-daily dosing. The trial will evaluate the treatment’s safety and its ability to improve kidney function and reduce disease activity.
Vilolelimab tested as a replacement for glococorticoids
Vilolelimab, previously known as IFX-1, is an antibody-based therapy that targets C5a, effectively and selectively blocking the protein. It was evaluated in two Phase 2 trials in people with AAV – the European IXCHANGE trial (NCT03895801) and the U.S. IXPLORE trial (NCT03712345).
In the IXCHANGE trial, which evaluated vilobelimab as a replacement for glucocorticoids alongside standard therapy, the treatment achieved remission rates comparable to standard-dose glucocorticoids while reducing steroid exposure and related toxicity. In the IXPLORE trial, which assessed vilobelimab as an add-on to standard care, the therapy was well tolerated, data showed.
In addition, Inflarx collaborator Staidson Biopharmaceuticals has generated promising data with BDB-001, a similar anti-C5a antibody produced using the same cell line as vilobelimab, under a license agreement granting development and commercialization rights in China.
Results from a Phase 1/2 study (NCT05197842) also demonstrated that BDB-001 was safe and led to partial AAV remission, while reducing the need for standard glucocorticoids. The company is now testing the treatment in a Phase 3 trial in China.
“With our anti-C5a antibody vilobelimab and our next-generation oral C5aR inhibitor izicopan, we have built a differentiated portfolio targeting this mechanism. We are committed to identifying the most efficient development pathway, with an overall goal for InflaRx of maximizing the value of these programs,” Riedemann said.
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