InflaRx's Oral C5aR Inhibitor INF904 Shows Biologic-Like Efficacy in Phase 2a Trials for Hidradenitis Suppurativa and Chronic Spontaneous Urticaria

InflaRx (搜索)搜索该公司 has reported promising topline results from its phase 2a clinical study of INF904查看药品详情, an orally administered small-molecule C5a receptor (搜索)搜索该靶点 (C5aR) antagonist, demonstrating early signals of efficacy in both hidradenitis suppurativa (搜索)搜索该疾病 (HS) and chronic spontaneous urticaria (搜索)搜索该疾病 (CSU). The preliminary data suggest biologic-like efficacy with a favorable safety profile, supporting further clinical development of this complement pathway inhibitor.

Hidradenitis Suppurativa Results Show Sustained Improvement

The HS phase 2a trial enrolled 29 evaluable patients across three dosing cohorts (60 mg, 90 mg, and 120 mg twice daily) for four weeks of treatment followed by a four-week observation period. The study demonstrated meaningful reductions in inflammatory lesion counts across all dose groups, with the highest dose (120 mg BID) showing an average decrease of 8.1 abscesses and nodules (AN) lesions.

Clinical response rates measured by HiSCR50 showed progressive improvement through treatment and follow-up. As Dr. Camilla Chong, chief medical officer at InflaRx (搜索)搜索该公司, explained: "If you look across those 3 doses, at week 4, we achieve just under 30% (HiSCR50) but from week 4 to week 8, the efficacy continues up to 40%." Pooled HiSCR50 rates reached approximately 44% at week 4 and 63% at week 8, indicating sustained benefit after drug discontinuation.

Particularly notable was the impact on draining tunnels, with reductions observed in up to 50% of patients at week 4. Pain improvements were substantial, with about 65% of patients achieving NRS30 response at week 4. Chong highlighted the patient-reported impact: "Patients actually feel a tremendous reduction in their pain… when patients have relief from their draining tunnels, it's no surprise that the pain goes."

Quality of life improvements were reflected in DLQI scores, which improved by a mean of 5-10 points, demonstrating tangible patient-reported benefits.

CSU Trial Demonstrates Activity Across Patient Subgroups

The CSU phase 2a portion included 30 evaluable patients randomized to INF904查看药品详情 60 mg or 120 mg BID for four weeks. At week 4, INF904 reduced mean UAS7 scores by -13.7 points in the 60 mg group and -7.9 points in the 120 mg group, with reductions persisting through week 8.

Patients with severe baseline disease (UAS7 ≥28) showed even greater improvement (-15.4), and those with concurrent angioedema demonstrated the most pronounced reduction (-18.7). Notably, UAS7 improvement extended to patients with low baseline IgE levels (<40 IU/L), representing the Type IIb autoimmune CSU phenotype, suggesting activity across immunopathologic subsets.

Disease control improvements were reflected in UCT7 scores, which increased by over 4 points on average, with roughly 30% of patients achieving UCT7 ≥12 ("well controlled").

Mechanism Offers Differentiation from Current Therapies

INF904查看药品详情 targets the C5a/C5aR axis, a key driver of neutrophil activation and downstream inflammatory cascades. Unlike monoclonal antibodies that neutralize circulating C5a, INF904 inhibits its receptor (C5aR1 (搜索)搜索该靶点) directly on immune and tissue cells. In preclinical and phase 1 studies, INF904 demonstrated rapid onset of C5aR blockade, achieving >90% inhibition of C5a-induced signaling.

Chong emphasized the mechanistic differentiation from current HS therapies: "You're blocking one mechanism… we know that HS is more heterogeneous than that… you need to block C5a." She proposed that neutrophil-rich tunnels may be particularly suited to C5aR blockade, and an oral small molecule may offer improved tissue penetration compared with biologic antibodies.

For CSU, Chong suggested that complement-driven neutrophilic inflammation may represent a parallel or complementary mechanism to mast cell activation: "There's the inflammatory milieu that you then need to actually work on. These things are already ongoing, so it will take a little bit of time, but with time, you see that deepening of effect."

Safety Profile Supports Continued Development

Safety profiles were favorable across both indications. In the HS cohort, no serious adverse events or safety signals were detected, with only three mild (grade 1) adverse events considered possibly or likely related to treatment. No laboratory abnormalities or discontinuations were attributed to INF904查看药品详情.

Similarly, in the CSU cohort, INF904查看药品详情 was well tolerated with no serious or severe treatment-related adverse events. One mild (grade 1) adverse event was deemed possibly related to study drug, consistent with prior phase 1 findings.

Future Positioning and Development Plans

InflaRx (搜索)搜索该公司 plans to prioritize HS development given the magnitude of unmet need, while continuing strategic exploration in CSU and potentially other neutrophilic dermatoses. Although Chong stressed that initial positioning would be pragmatic rather than first-line, she emphasized potential long-term evolution: "There is no reason why in the future, INF904查看药品详情 should not be positioned as a first-line treatment."

The oral convenience combined with biologic-like efficacy presents a potentially disruptive therapeutic option. For patients who prefer to avoid injections or who have cycled through multiple IL-17 (搜索)搜索该靶点 inhibitors, an oral C5aR inhibitor could shift treatment sequencing.

As Chong summarized: "What I would really like patients to have is choices, so you get what is right for you, not just because it's the only thing that's available."