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If at first you don't succeed...
PLANEGG, Germany—InflaRx is reporting mixed results about their keystone drug candidate, IFX-1, a first-in-class monoclonal anti-human complement factor C5a developed to block the behavior of C5a with an attraction towards its target in human blood. According to the company, this is significant in that “IFX-1 leaves the formation of the membrane attack complex (C5b-9) intact as an important defense mechanism, which is not the case for molecules blocking the cleavage of C5. IFX-1 has been demonstrated to control the inflammatory response driven tissue and organ damage by specifically blocking C5a as a key “amplifier” of this response in preclinical studies.”
While it is believed to be the first monoclonal anti-C5a antibody introduced into clinical development, the results in ongoing clinical trials are tepid. Approximately 300 people have been treated with IFX-1 in clinical trials, and the antibody has been shown to be well tolerated. IFX-1 is currently being developed for various inflammatory indications, including hidradenitis suppurativa (HS), ANCA-associated vasculitis and pyoderma gangrenosum.
Earlier this month, the company released the top-line results for the SHINE Phase 2b trial of IFX-1, which they hoped would be for people with HS, an orphan skin disease with limited effective treatment. The company was disappointed to report that their study showed that IFX-1 had no significant dose response.
“Unfortunately, we had to report a failure on the analysis of the primary endpoint (dose-dependent effect of IFX-1 on the [Hidradenitis Suppurativa Clinical Response] (HiSCR) at week 16) of the trial, while we reported a statistically significant effect of IFX-1 on the Dermatology Life Quality Index and a trend in AN count reduction (AN = abscess and inflammatory nodule count) when compared to placebo treatment,” asserted a statement from the company. “The DLQI was originally used (amongst other parameters) to validate the HiSCR.”
After 16 weeks, with 179 patients at over 40 sites, researchers looked at the HiSCR and found no significant response, especially since the placebo arm showed an unusually high response rate in the study. This was anomalous to placebo results from other studies, signifying the need for in-depth analysis of the validated full data set for the initial placebo-controlled double-blinded part of the first four months of the SHINE trial.
Othmar Zenker, chief medical officer of InflaRx, said: “We are disappointed that we were not able to demonstrate a significant signal on dose response for the treatment with IFX-1. While we are still analyzing additional data, we note that the trial demonstrated an unusually high placebo HiSCR rate at week 16.”
Despite these disappointing results, the company continues to explore the potential of IFX-1, not just in trying to better understand this recent data but also delving into other diseases. InflaRx is also testing IFX-1 on other rare but debilitating auto-immune diseases, including anti-neutrophil cytoplasmic antibodies, or ANCA-associated vasculitis, and related acute inflammatory processes. Likewise, as the company noted in another June news release, they have treated the first patient suffering from pyoderma gangrenosum (PG) in their Phase 2a clinical trial.
PG is an uncommon, but devastating, neutrophilic-driven, autoinflammatory disease, typified by severe ulcerated pustules under the skin, predominantly on the legs. Its cause is not fully understood, but patients with PG have demonstrated elevated immune mediators. The exact prevalence of PG is not yet known, but it estimated to impact one per 100,000 people.
InflaRx is engaged in an open-label Phase 2a proof-of-concept study which will eventually enroll approximately 12 patients with moderate to severe PG, initially in Canada. Patients will be treated with IFX-1 for 12 weeks with a three-month follow-up period. According to the release, the main objectives of the study are the evaluation of the safety and efficacy of IFX-1 in patients with PG, as determined by a responder rate defined as Physician Global Assessment ≤3 of the target ulcer at various timepoints and time to complete closure of the target ulcer, in comparison with historical data.
The company noted that it is pleased to have Dr. Afsaneh Alavi, an assistant professor of dermatology at the University of Toronto, as the principle investigator for this study. “Pyoderma gangrenosum is a debilitating disease with limited treatment options,” stated Alavi. “A high medical need exists to develop new treatments, especially ones with novel modes of action. We look forward to seeing the results from this trial with IFX-1 in this patient population.”