First Effective Nanobody in Myasthenia Gravis Therapy

Дата публикации: 27-07-2026 00:00:00

In generalized myasthenia gravis (gMG), a continuously increasing spectrum of immunomodulatory agents with different mechanisms of action have been studied, including T- and B-cell directed drugs and drugs acting on downstream antibody-metabolism, such as neonatal Fc receptor (FcRn) and complement inhibitors. Because of the particular pathogenic properties of anti–acetylcholine receptor antibody (AChR-Ab) of the IgG1 and IgG3 type, blocking of complement factor 5 (C5) has been established as a rapidly effective therapeutic principle in generalized AChR-Ab–positive MG during the last decade. Inhibition of complement factor 5 (C5) activation (and thereby cleavage of C5 into C5a and C5b) prevents from membrane attack complex mediated structural damage of the postsynaptic muscle end plate contributing to impaired neuromuscular transmission in AChR-Ab–positive gMG. Apart from already approved C5 inhibitors like eculizumab, ravulizumab, and zilucoplan, further agents directed against C5 but also against other complement factors have been developed. Gefurulimab (formerly ALXN1720), a bispecific nanobody, specifically targets C5 and also human serum albumin (HSA) by a C-terminal C5-binding heavy domain of heavy chain (VHH) connected to an N-terminal albumin-binding VHH via a flexible linker. Binding to HSA extends half-life time of gefurulimab by FcRn-mediated recycling.

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