Myasthenia Gravis: Emerging Therapies

Myasthenia Gravis is a chronic autoimmune, neuromuscular disease that causes weakness in the skeletal muscles that worsens after periods of activity and improves after periods of rest. These muscles are responsible for functions involving breathing and moving parts of the body, including the arms and legs. It is characterized by muscular fatigue leading to extreme weakness. The fatigue is caused by the loss of ability to convert nerve impulses into muscle contraction. The disease affects muscles controlling voluntary movement including those associated with actions such as swallowing and breathing and usually begins in a mild form. Typical first symptoms are associated with the eyelid, sight, swallowing, and speech. Focal MG usually develops more or less rapidly into generalized MG with symptoms that appear in the arms and abdomen and subsequently in the legs and respiratory muscles.

Various diagnostic tests such as electro-diagnostics, diagnostic imaging, pulmonary function tests, and other tests are used for the diagnosis of Myasthenia Gravis. Thymectomy, Monoclonal antibody, Anticholinesterase medications, and Immunosuppressive drugs are recommended for the treatment of myasthenia gravis. Several pharmaceutical companies such as CuraVac, argenx BVBA, Cartesian Therapeutics, Momenta Pharmaceuticals, Inc., RemeGen, and others are involved in the development of novel therapies for the treatment of Myasthenia Gravis.

CuraVac (CV-MG01)

Myasterix (CV-MG01) is an investigational therapeutic vaccine being developed by Curavac to alleviate the symptoms of myasthenia gravis. Myasterix is likely to have fewer side effects and a simpler method of administration than other therapies. The Myasterix vaccine induces the body to produce a different type of antibody, which binds to autoantibodies and T-cell receptors associated with myasthenia gravis. Obstructing receptors of the anti-AChR T-cells with the Mysterix-produced antibody prevents autoimmune production of anti-AChR antibodies. This is expected to unblock the AChR, restoring neuromuscular communication via acetylcholine successfully binding to its receptor.

Myasterix, is currently investigated under a clinical trial study. The Study CV-0002 is the first clinical trial administering CV-MG01 in humans. This clinical trial is a safety and proof-of-concept study (proof of mechanism of action) intended to assess the safety, tolerability, and immunogenic response following three subcutaneous injections of CV-MG01 as a potential therapeutic vaccine / active immunotherapy in myasthenia gravis (MG) patients.

Argenx BVBA (ARGX-113/ Efgartigimod)

Efgartigimod is designed as a first-in-class investigational antibody fragment to target the neonatal Fc receptor (FcRn). Efgartigimod is being evaluated for the treatment of patients with severe autoimmune diseases with confirmed presence of pathogenic immunoglobulin G, IgG autoantibodies, where a severe unmet medical need exists.

Cartesian Therapeutics (Descartes-08)

Descartes-08 is a CD8+ CAR-T investigational therapy that targets cells expressing B-cell Maturation Antigen (BCMA), a protein expressed by all plasma cells. Descartes-08 is engineered to have a defined and predictable half-life, enabling repeat dosing to maximize potency while minimizing the risk of toxicity

UCB Biopharma S.P.R.L. (Rozanolixizumab)

Rozanolixizumab is a subcutaneously administered, humanized monoclonal antibody that specifically binds, with high affinity, to human FcRn. It has been designed to block the interaction of FcRn and IgG, inhibiting IgG recycling and inducing the removal of pathogenic IgG autoantibodies. Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases, including ITP, myasthenia gravis (MG) and chronic inflammatory demyelinating polyneuropathy (CIDP), by driving removal of pathogenic IgG autoantibodies

Momenta Pharmaceuticals, Inc.( M281/ Nipocalimab)

Nipocalimab (M281) is a fully human, anti-FcRn (neonatal Fc receptor), aglycosylated IgG1 monoclonal antibody. Nipocalimab (M281) has the potential of improving the clinical signs and symptoms of MG by blocking FcRn-mediated IgG recycling, thereby reducing pathogenic autoantibodies including the most common autoantibodies, anti-AChR and anti-MuSK. Nipocalimab, is investigated under clinical trial. The purpose of this study is to evaluate the safety, tolerability, and efficacy of M281 administered to participants with generalized myasthenia gravis (gMG) who have an insufficient clinical response to ongoing standard of care therapy.

Immunovant Sciences GmbH (IMVT-1401)

The investigational drug product candidate, IMVT-1401 (formerly known as RVT-1401), is a novel, fully human monoclonal antibody targeting the neonatal Fc receptor (FcRn). IMVT-1401 has the potential to address a variety of IgG-mediated autoimmune diseases as a subcutaneous injection. The FcRn receptor facilitates IgG recycling. IMVT-1401 enhances the degradation of IgG by targeting FcRn and preventing endogenous IgG from binding. This increased catabolism of IgG may curtail the harmful immune response exhibited by auto-antibodies.

Catalyst Pharmaceuticals, Inc. (Amifampridine Phosphate)

Amifampridine, a neuronal potassium channel blocker, is used for the treatment of MuSK-positive myasthenia gravis. Currently, Catalyst is enrolling patients into a phase III trial examining amifampridine  for the treatment of Myasthenia Gravis. The MuSK Trial is a phase III, randomized, double-blind, placebo-controlled, parallel-group study evaluating the safety, tolerability, and efficacy of amifampridine in patients with MuSK-MG and a small sample of patients with AChR-MG. Amifampridine has received the Orphan Drug Designation from the Food and Drug Administration FDA for the treatment of patients with myasthenia gravis.

RemeGen (RC18)

Investigational candidate RC18 is a fusion antibody created by RemeGen scientists to target signaling factors involved in the development and survival of B cells, the cell responsible for generating antibodies. RC18 is a fusion of a TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactors) protein and the IgG protein.

RC18 binds to BLyS (B lymphocyte stimulator) and APRIL (a proliferation-inducing ligand), preventing these cell-signaling molecules from binding to TACI proteins on the surface of the B cell. This inhibits the development and survival of mature B cells, preventing the formation of autoantibodies.

Emerging Pipeline Landscape of Myasthenia Gravis

Company NameProduct NameMechanism of ActionRoute of AdministrationStage of development
CuraVacCV-MG01Acetylcholine ModulatorsSubcutaneousPhase I/II
argenx BVBAARGX-113FcRn/ Neonatal Fc receptor AntagonistsIntravenousPhase III
Cartesian TherapeuticsDescartes-08CD8 + CART TherapyIntravenousPhase I/II
UCB Biopharma S.P.R.L.Rozanolixizumab/UCB7665Anti-(FcRn) antibodySubcutaneous Phase III
Momenta Pharmaceuticals, Inc.M281/ NipocalimabAnti-FcRn AntibodyIntravenousPhase II
Immunovant Sciences GmbHIMVT-1401  Neonatal Fc Receptor AntagonistsSubcutaneousPhase II
DAS-MG, IncDAS-001Acetylcholinesterase InhibitorsNAPhase II
Catalyst Pharmaceuticals, Inc.Amifampridine PhosphateNeuronal Potassium Channel BlockerOralPhase III
RemeGenRC18
Fusion protein
BLyS/APRIL
subcutaneousPhase II

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