TouchDERMATOLOGY coverage from AAD 2025:
Vilobelimab, a first-in-class monoclonal anti-human complement factor C5a antibody, is showing promise as a potential treatment for pyoderma gangrenosum (PG), a rare and often chronic autoimmune inflammatory skin disorder characterized by painful ulcerations.1
Despite its severity, PG currently has no approved treatments in the USA or Europe, leaving patients with limited options and a significant need for effective therapy. While its exact pathophysiology remains unclear, research suggests PG is complex and multifactorial, involving dysregulation of the innate immune system and overactivation of neutrophils.2
At the American Academy of Dermatology (AAD) Annual Meeting, held in Orlando, FL, 7–11 March 2025, new phase IIa data on vilobelimab were presented. To gain insight into these findings, we spoke with study investigator, Dr Ben Kaffenberger from The Ohio State University, Columbus, OH, USA.3,4
Q. What prompted the investigation of vilobelimab as a potential treatment for pyoderma gangrenosum?
We know that PG is a neutrophilic disorder characterized by an excessive number of neutrophils. Neutrophils are attracted by the chemoattractant molecule, complement component 5a (C5a), which plays a key role in inflammation. Vilobelimab, as a monoclonal anti-human complement factor C5a antibody, specifically targets and blocks C5a activity, while preserving the C5b-9 complex, a crucial defense mechanism of the innate immune system. By doing so, it is thought vilobelimab could help control the active phase of the disease.
Q. What are the aims and design of the phase IIa study?
The study was an open-label, international phase IIa trial designed to evaluate the safety and tolerability of vilobelimab in patients with PG.
The study enrolled 19 patients who were allocated to one of three different dosing cohorts. Group 1 (n=6) received 800 mg, Group 2 (n=6) received 1,600 mg and Group 3 received 2,400 mg every 2 weeks for 26 weeks, all patients were assigned to a group after completing a run phase of 800 mg vilobelimab on Days 1, 4 and 8. Patients only had their dose escalated once safety and tolerability at the prior lower dosage had been confirmed.
The primary endpoint was the assessment of safety and tolerability, focusing on the occurrence of adverse events (AEs). Safety assessments included evaluating the occurrence, severity, seriousness, and causality of AEs, along with monitoring vital signs, electrocardiograms (ECGs) and laboratory safety parameters.
The key secondary endpoints included pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, along with an overall effectiveness analysis of the treatment. Effectiveness was measured using tools designed to assess the level and time to ulceration closure.
Q. What have been the findings in terms of safety & tolerability across the varied dose groups?
Overall, all three dose cohorts were well tolerated. Reported AEs were mostly mild to moderate in nature, and noted in 15 of the 19 enrolled patients (6 [100.0%] in Group 1, 4 [66.7%] in Group 2, 5 [71.4%] in Group 3). Most were skin and subcutaneous tissue disorders (9 [47.4%] patients) and infections/infestations (8 [42.1%] patients ). Two AEs of special interest (AESIs) were reported. This included one case of erysipelas that led to hospitalization. Another patient developed a rash thought to be a delayed hypersensitivity reaction to the medication.Â
Overall, no dose-related reactions were reported with the highest dose being evaluated as safe as the lowest dose. Additionally, no infusion-related reactions or clinically relevant findings for vital signs, ECGs, haematology, clinical chemistries or urinalysis were reported.
Q. What were the key pharmacokinetic and pharmacodynamic findings from these data?
We found that patients tended to have elevated C5a levels at baseline. Additionally, those with elevated C5a appeared to be better responders to vilobelimab. In fact, 7 out of 9 patients who achieved complete ulcer closure also had elevated C5a concentrations at baseline.
We also observed expected PK trends. Higher geometric means (GM) vilobelimab trough concentrations were seen with the higher doses. Additionally, plasma C5a levels remained low throughout the study, particularly in the higher dosing Groups 2 and 3. There was a clear dose–response relationship, where higher doses of vilobelimab led to greater suppression of plasma C5a in participants. The PK/PD analysis suggested that doses >1600 mg given bi-weekly of vilobelimab are needed in patients with severe PG to suppress C5a. No consistent increases or decreases in C3a concentrations were observed by dose or visit in the study.
Q. What are the next steps in advancing the potential of vilobelimab for patients with pyoderma gangrenosum?
There is an ongoing multi-national, randomized, double blind, placebo-controlled phase III study (NCT05964413), which is currently about 50% enrolled. This trial is focused on evaluating the efficacy of vilobelimab in PG and serves as the pivotal study for FDA approval. Based on the phase II findings, where no dose-dependent AEs were observed, the highest dose of 2,400 mg every 2 weeks has been selected for the phase III trial alongside a low dose of corticosteroids, and a placebo with the same corticosteroid regimen. Corticosteroid treatment will commence on day 1 and be tapered off within the initial 8 weeks. The primary endpoint of the study aims to achieve complete closure of the target ulcer within 26 weeks post-treatment initiation.
Associated abstracts
- Himed S, Tawfik H and Kaffenberger B. Treatment of pyoderma gangrenosum with vilobelimab. JAMA Dermatol. 2024;160(8):898–9
- Afsaneh Alavi, Dermatology Meeting News 2022: Phase 2 Trial of Vilobelimab for Ulcerative Pyoderma Gangrenosum. TouchIMMUNOLOGY. 4 May 2022
- Alavi A, Kaffenberger B, Tawfik H, et al. Vilobelimab safety in pyoderma gangrenosum patients: A phase 2a explorative dose-finding study. Poster ID 63560, AAD, 7–11 March 2025
- Giamarellos-Bourboulis E, Kanni T, Tawfik H, et al. Pharmacokinetic/pharmacodynamic analysis of vilobelimab demonstrates a significant reduction of C5a levels in hidradenitis suppurativa patients. Poster ID: 63454, AAD, 7–11 March 2025
Disclosures: Ben Kaffenberger has acted as consultant for InflaRx, Boehringer-Ingelheim, Elsevier, ADC Therapeutics, Lilly, Novocure and Novartis; and has received grant/research support from InflaRx, Boehringer-Ingelheim, Merck and BMS.
This content has been developed independently by Touch Medical Media for touchDERMATOLOGY and is not affiliated with the American Academy of Dermatology (AAD). Unapproved products or unapproved uses of approved products may be discussed by the faculty; these situations may reflect the approval status in one or more jurisdictions. No endorsement of unapproved products or unapproved uses is either made or implied by mention of these products or uses by Touch Medical Media or any sponsor. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
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Editor: Gina Furnival, Senior Editorial Director
Cite: Kaffenberger B. Latest encouraging vilobelimab data in pyoderma gangrenosum. TouchDERMATOLOGY. 25 March, 2025
