PG is a rare ulcerative skin disorder that can lead to chronic painful and difficult to treat wounds. It occurs in people in their 40s and 50s. Many PG patients also suffer from other autoimmune disorders, including inflammatory bowel diseases like ulcerative colitis, arthritides like rheumatoid arthritis, and hematological diseases such as multiple myeloma.
Patients suffer from severe pain, long healing times, and frequent relapses. There are no drugs currently approved for the treatment of PG. Current treatment options include the use of systemic immunosuppression in rapidly progressing cases. However, prolonged systemic use of corticosteroids or cyclosporin increases the likelihood of serious side effects and many patients do not respond to this type of treatment or relapse. For less severe cases, topical or intralesional treatments can be used, including topical steroids. Response rates to newer therapies with biologics vary widely. Thus, a high unmet medical need exists for effective treatment options for this painful and debilitating disease.
The precise pathogenesis of PG is not fully understood, but it is known that an inflammatory dysregulation involving mostly neutrophils plays a role. Other potential contributing factors include: cytokine signaling by T cells and macrophages, as well as genetic mutations.
Diagnosis is based on the exclusion of other conditions. Lesions are likely autoinflammatory and characterized by the presence of neutrophils in the absence of infection. An additional characteristic feature of PG is pathergy, an overreaction to skin injuries or worsening of existing wounds induced by minimal insult.
C5a is a key factor for neutrophil tissue infiltration and neutrophil activation which are believed to play a key amplifying role in PG. Thus, C5a inhibition may be able to prevent neutrophil infiltration and activation in PG patients. Given the demonstrated activity of C5a inhibition by vilobelimab in another neutrophil-driven skin disorder, Hidradenitis Suppurativa, InflaRx has conducted a Phase II clinical study.
In October 2021, InflaRx released positive interim results. A total of 19 patients were enrolled in a multi-center, proof-of-concept, open-label Phase IIa study evaluating the safety and efficacy of vilobelimab in patients with PG. Efficacy is being evaluated by a responder rate defined as a Physician Global Assessment (PGA) score of ≤3 of the target ulcer at various timepoints and time to complete closure (remission) of the target ulcer. Over a treatment period of 26 weeks, patients were treated biweekly with vilobelimab 800mg, 1600mg or 2400mg, after an initial run-in phase with three doses of 800mg on days 1, 4 and 8. Per protocol, a dose increase to the next higher dosing group was possible upon disease assessment on day 57. Following the treatment period, patients continued to be observed for a period of two months, which is ongoing for the third cohort.
In the third and final dosing cohort at 2400mg biweekly, six of the seven patients achieved clinical remission with a PGA score of ≤1, which reflects a closure of the target ulcer. All patients in cohort 3 had elevated C5a levels at baseline that were continuously suppressed after initiation of vilobelimab.
InflaRx previously reported data for ten evaluable patients in the first two dose cohorts at day 99. The patient in the second dosing cohort demonstrating complete target ulcer closure had been increased from the 1600mg dose group to the highest dose of 2400mg dose on day 57 of the study, and the ulcer closed after the dose escalation. At day 99, this patient had a PGA score of 1, and by the end of the treatment period at day 189 had a PGA score of 0.
Overall, vilobelimab was well tolerated in the study. From all cohorts, two patients had related serious adverse events (SAEs) that were reported: One patient experienced an erysipelas leading to hospitalization (judged as non-related by sponsor), another developed a rash due to a delayed hypersensitivity reaction and withdrew from the study (which had been previously disclosed from cohort 2). No dose-related AEs were found. Overall, the observed AE profile was in line with the underlying diseases.
Final results including the observational period were published in the Q1 2022.