AAV is a rare, life-threatening autoimmune disease with a relapsing nature, characterized by necrotizing vasculitis (inflammation of blood vessels) predominantly affecting small vessels associated with anti-neutrophil cytoplasmic antibodies, or ANCA, directed to myeloperoxidase (MPO), or proteinase 3 (PR3). The disease involves three disease entities: 1) GPA, granulomatosis with polyangiitis (known as Wegener's Granulomatosis); 2) MPA, microscopic polyangiitis; and 3) eGPA, eosinophilic granulomatosis with polyangiitis (known as Churg-Strauss syndrome).
AAV is registered as an orphan disease with a prevalence of one to five per 10,000 and a reported incidence between 0.07 and 1.2 per 100,000, with approximately 40,000 patients in the US and 75,000 in Europe (SOURCE: www.orpha.net; Watts et al 2015).
The disease is characterized by life-threatening flare phases affecting kidney function and other organs leading to organ dysfunction and failure and is fatal unless treated appropriately. Since AAV is life-threatening, it is crucial to induce remission rapidly when presenting with a flare. The treatment to induce remission differs from maintenance therapy.
The disease-promoting role of C5a for this disease has been well established in published scientific literature, whereby a priming effect of C5a for neutrophils appears to be the essential factor leading to neutrophil-related damage of the endothelial cells in blood vessels. In addition, patients with acute AAV disease have significantly elevated complement activation parameters in their plasma when compared to AAV patients in remission. Numerous groups have established the importance of C5a for this disease while C6 deficiency in mice does not lead to improvement, indicating that MAC formation may not play a major role in this disease.
The current treatment regimen to induce remission uses a combination of High Dose Glucocorticoids (HDGCs), together with either rituximab or cyclophosphamide. The long lasting HDGC therapy is associated with significant side effects and additional life-threatening risks for patients. Even in patients achieving remission, major relapses can occur over time. Thus, a high unmet medical need for these patients exists for more effective and less side effect carrying therapies.
Based on the eminent role of C5a in the progression of inflammation in this life-threatening disease, InflaRx is currently conducting two clinical studies. One study in the US is evaluating the safety of IFX-1 in addition to standard of care, and one study in Europe is evaluating the potential of IFX-1 to replace HDGCs.