Orphan Drug Designation for Argenx’s ARGX-113—Hopeful News for Myasthenia Gravis Community

29th September 2017 (Last Updated September 29th, 2017 14:59)

On September 25, the FDA granted Orphan Drug Designation for Argenx’s lead clinical-stage product candidate, ARGX-113, for the treatment of myasthenia gravis (MG). The designation, which came one month after the EMA approval of the first complement-based therapy, Soliris, for the treatment of refractory generalized MG, is deemed welcoming and important news to the myasthenia gravis community, given the limited effective and sustainable treatments for this rare disease. ARGX-113 is also the second biologic that was granted the Orphan Drug Designation for the MG indication, and what makes this pipeline drug so attractive is that it targets a broader MG patient population, generalized MG (gMG), in comparison with Soliris’ smaller refractory gMG group, which is a clear bonus over its biologic competitor.

On September 25, the FDA granted Orphan Drug Designation for Argenx’s lead clinical-stage product candidate, ARGX-113, for the treatment of myasthenia gravis (MG). The designation, which came one month after the EMA approval of the first complement-based therapy, Soliris, for the treatment of refractory generalized MG, is deemed welcoming and important news to the myasthenia gravis community, given the limited effective and sustainable treatments for this rare disease. ARGX-113 is also the second biologic that was granted the Orphan Drug Designation for the MG indication, and what makes this pipeline drug so attractive is that it targets a broader MG patient population, generalized MG (gMG), in comparison with Soliris’ smaller refractory gMG group, which is a clear bonus over its biologic competitor.

MG is a relatively rare autoimmune neuromuscular disorder associated with severe muscle weakness that is triggered by immunoglobulin G (IgG) autoantibodies. These autoantibodies recognize and attack critical signaling proteins in the nerve-muscle junction, leading to impairment of communication signals. Basically, MG cannot be cured completely and requires long-term management. However, current treatments of MG are dominated by untargeted, symptomatic therapies such as acetylcholinesterase inhibitors, as well as steroids and immunosuppressants. These treatments are unable to restore muscle strength to normal in most patients. Newer treatments with monoclonal antibodies are a welcome addition to the treatment regimen, such as Soliris, Rituxan (which is currently used off-label), and others. These biologic agents are promising but their use is currently restricted to patients with refractory disease. However, key opinion leaders (KOLs) interviewed by GlobalData expressed concerns about these biologics not being able to cure the root problem of MG, as it is unlikely that they will restore muscle strength to a normal level in all patients. As such, a huge unmet need remains for targeted and effective therapy that allows for the restoration of muscle strength to normal or near normal.

Among the early-phase candidates, targeting of neonatal Fc receptors (FcRns) is the first interesting line of research highlighted by KOLs. FcRns are involved in prolonging IgG half-life, which contributes towards enhanced immunity but also promotes the accumulation of pathogenic IgG autoantibodies and increased autoimmunity. While the pathogenesis of autoimmune antibodies is not fully understood, it has emerged that FcRns are a potentially fruitful target for autoimmune diseases including myasthenia gravis. ARGX-113 is an Fc-engineered human monoclonal antibody that has been modified by the Argenx proprietary ABDEG technology to enhance its affinity for the FcRn beyond that of normal IgG antibodies. As a consequence, ARGX-113 blocks antibody recycling, leading to fast depletion of the IgG autoantibodies. Currently, ARGX-113 is in a Phase II proof-of-concept study, with topline results anticipated in Q1 2018. It is also under investigation for treatment of other IgG-mediated autoimmune diseases, including pemphigus vulgaris and immune thrombocytopenia.