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 (IFX-1) in another neutrophil-driven skin disorder, Hidradenitis Suppurativa, InflaRx is currently conducting a Phase II clinical study to investigate a potential benefit of vilobelimab for patients suffering from PG. Of the first 5 patients dosed, two achieved complete remission. The study continues to enroll patients with the addition of two higher dose cohorts.
