Ravulizumab for the treatment of myasthenia gravis

Figures & data

Table

Drug name	Ravulizumab
Phase	III
Indication	AChR-positive generalized myasthenia gravis
Pharmacology description/mechanism of action	Complement inhibiting monoclonal antibody, specifically directed against C5
Route of administration	Intravenous
Pivotal trial	Randomized, double-blind, placebo-controlled, multicenter, phase III CHAMPION MG study (NCT03920293)

Table 1. New myasthenia gravis therapies approved and under study.

Study phase/Authority approval	Drug	Mechanism of action	Route of administration	Clinicaltrial.gov number
FDAapproved	Eculizumab	Anti-C5	IV	NCT01997229
	Ravulizumab	Anti-C5	IV	NCT03920293
	Efgartigimod	FcRn inhibitor	IV	NCT03770403
Phase III	ALXN1720	Anti-C5	SC	NCT05556096
	Zilucoplan	Anti-C5	SC	NCT04115293
	Pozelimab+cemdisiran	Anti-C5	SC	NCT05070858
	Inebilizumab	Anti-CD19	IV	NCT04524273
	Satralizumab	Anti-IL6	SC	NCT04963270
	Nipocalimab	FcRn inhibitor	IV	NCT04951622
	Efgartigimod	FcRn inhibitor	SC	NCT04818671
	Rozanolixizumab	FcRn inhibitor	SC	NCT04650854
Phase II	ALXN2050	Anti-C5	PO	NCT05218096
	Belimumab	BAFF	IV	NCT01480596
	Iscalimab	CD40	IV	NCT02565576
	Batoclimab	FcRn inhibitor	SC	NCT03863080
	TAK-079	Anti CD38	SC	NCT04159805

Note: BAFF B-cell activating factor, FcRn neonatal Fc receptor, IV intravenous, SC subcutaneous, PO per os (oral)

Figure 1. Pathophysiology of complement activation in MG: anti-acetylcholine (Ach) receptor (AChR) antibodies activate the complement cascade through the classical pathway by binding C1q con the Fc domain. The subsequent formation of C5 convertase initiates the terminal pathway which ultimately leads to the formation of the membrane attack complex (MAC), a lytic pore on the postsynaptic membrane. The final effect is a focal lysis of the neuromuscular junction (NMJ), with disruption of the postsynaptic folds and loss of AChRs. Ravulizumab binds with high affinity to C5, inhibiting its enzymatic cleavage and thereby preventing the MAC formation. Created with Biorender.com.