What are the different FcRn (Fc receptor neonatal) inhibitor treatments, such as efgartigimod (efgartigimod), for myasthenia gravis?

FcRn Inhibitor Treatments for Myasthenia Gravis

Efgartigimod is the only FDA-approved FcRn inhibitor for treating generalized myasthenia gravis in adult patients who are anti-acetylcholine receptor (AChR) antibody positive, with several other FcRn inhibitors currently in clinical development. 1

Mechanism of Action of FcRn Inhibitors

FcRn inhibitors work by blocking the neonatal Fc receptor (FcRn), which normally:

• Prevents IgG catabolism by impeding lysosomal degradation
• Facilitates extracellular release of IgG at physiological pH
• Extends IgG half-life in circulation 2

By blocking FcRn, these medications:

• Enhance the catabolism of IgG antibodies, including pathogenic autoantibodies
• Produce effects similar to plasma exchange but with fewer safety concerns
• Reduce circulating levels of pathogenic autoantibodies in myasthenia gravis 2

Available FcRn Inhibitor Treatments

1. Efgartigimod (VYVGART)

• FDA approval status: Approved for generalized myasthenia gravis in adult patients who are anti-AChR antibody positive 1
• Administration routes:
  • Intravenous (IV): 10 mg/kg administered over one hour once weekly for 4 weeks
  • Subcutaneous (SC): Also approved (Vyvgart Hytrulo) 3
• Dosing: For patients weighing 120 kg or more, the recommended dose is 1200 mg per infusion 1
• Treatment cycle: Subsequent cycles based on clinical evaluation; safety of initiating cycles sooner than 50 days from the start of the previous cycle has not been established 1
• Efficacy: Significant and clinically meaningful improvements in myasthenia gravis symptoms with reproducible, durable effects maintained over the long term 3
• Common adverse effects: Respiratory tract infections, headache, and urinary tract infection 1

2. FcRn Inhibitors in Development

Several other FcRn inhibitors are currently in various stages of clinical development:

• Rozanolixizumab: Under review by health authorities 2
• Nipocalimab: Phase 3 trials underway 2
• Batoclimab: Phase 3 trials underway 2

Clinical Efficacy and Real-World Experience

Efgartigimod Clinical Outcomes

• 75-86.3% of patients experience a clinically significant improvement (≥2 points in MG-ADL score) after the first treatment cycle 4, 5
• Effect duration typically ranges between 4-12 weeks 4
• Allows for significant reductions in prednisone doses (steroid-sparing effect) 4
• Improves health-related quality of life 3

Real-World Experience

• UK study of 48 treatment-resistant patients showed mean MG-ADL score reductions of 3.4-4.6 points across treatment cycles 5
• 96% of patients remained on efgartigimod at the end of the study, indicating good tolerability and efficacy 5
• Two major clinical response patterns observed in real-world use 4

Potential Additional Mechanisms Beyond IgG Reduction

Recent research suggests efgartigimod may have immunoregulatory effects beyond simple IgG reduction:

• Increases percentage of CD19+/CD27+ memory B cells and CD27+/CD138+ plasma cells 6
• Induces non-pathogenic regulatory plasma cells 6
• Upregulates CD38, LAG3, and IL-12a genes 6

Safety Considerations

• Generally well-tolerated with mostly mild adverse events 4, 5
• Most common adverse events:
  • IV formulation: Headache and infections 3
  • SC formulation: Injection-site reactions 3
• Potential for infections: Consider delaying administration in patients with active infection 1
• Hypersensitivity reactions: Anaphylaxis, hypotension, angioedema, dyspnea, and rash have been reported 1
• Infusion-related reactions may occur 1
• Drug interactions: May reduce effectiveness of medications that bind to FcRn 1

Treatment Algorithm for FcRn Inhibitor Use in MG

1. Patient selection: Adult patients with generalized MG who are anti-AChR antibody positive
2. Evaluate vaccination status: Consider age-appropriate vaccines before initiating treatment
3. Initial treatment cycle: 10 mg/kg IV once weekly for 4 weeks
4. Monitor response: Using validated scales like MG-ADL
5. Determine subsequent cycles: Based on clinical response, typically every 50+ days
6. Consider personalized approach: Some patients may benefit from preventive treatment until clinical stabilization, followed by discontinuation and periodic evaluations 4

FcRn inhibitors represent a significant advancement in the treatment of myasthenia gravis, offering targeted reduction of pathogenic antibodies with favorable safety profiles compared to traditional immunosuppressive therapies.