FDA Approves Expanded Use of Eculizumab for Pediatric Myasthenia Gravis

The FDA has granted approval for an expanded indication of eculizumab (Soliris; Alexion/AstraZeneca) to include both adult and pediatric patients who are 6 years of age or older with generalized myasthenia gravis (gMG) who are antiacetylcholine receptor (AChR) antibody positive. With the approval, it becomes the first and only treatment for pediatric patients living with the disease.¹

The use of eculizumab in pediatric patients for this indication was supported by evidence from a well-controlled trial in adults with additional pharmacokinetic and safety data in pediatric patients with gMG who are 12 years of age and older, as well as pharmacokinetic and safety data in other pediatric populations in the range of at least 6 years to younger than 12 years. In a 26-week, single-arm study of 11 pediatric patients with gMG 12 to 17 years of age, adverse reactions were consistent with those observed in adults living with the disease.

In terms of administration, eculizumab is given by an intravenous infusion over 35 minutes to adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump. The injection is administered in doses of 300 mg/30 mL (10 mg/mL) as a clear, colorless solution in a single-dose vial. It remains contraindicated for patients with unresolved serious Neisseria meningitidis infection.

Eculizumab, first approved for paroxysmal nocturnal hemoglobinuria (PNH) in 2007, is a monoclonal antibody that targets the complement system, specifically inhibiting the protein C5. By preventing the cleavage of C5 into C5a and C5b, it halts the formation of the membrane attack complex, which is a critical mediator of complement-related tissue damage. For context, the complement system is a part of the immune system and plays a significant role in inflammation and the destruction of pathogens, but its dysregulation can lead to autoimmune and other complement-mediated diseases.

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The therapy comes with several important safety information, including a boxed warning label. Patients may only access the therapy through a restricted program under a Risk Evaluation Management Strategy (REMS) program, called Ultomiris and Soliris REMS, because of the risk of serious meningococcal infections. To be eligible, patients must complete or update their meningococcal vaccine(s) at least 2 weeks before the first dose of eculizumab. If patients experience symptoms of a serious meningococcal infection, they are advised to call their healthcare provider or get emergency care immediately. These symptoms include fever alone, fever with high heart rate, fever and headache, fever and a rash, confusion, muscle aches with flu-like symptoms, headache with nausea or vomiting, headache with a stiff neck or stiff back, or eye sensitivity to light.

Eculizumab gained its second indication in 2011 for the treatment of atypical hemolytic uremic syndrome, a life-threatening condition leading to blood clot formation and organ damage. Years later, in 2017, it was approved for adults with gMG with AChR antibodies, helping to reduce complement-mediated damage to the neuromuscular junction, thus improving symptoms of weakness. It made history in 2019, becoming the first approved therapy for patients with neuromyelitis optica spectrum disorder (NMOSD), a rare, autoimmune disorder that affects the central nervous system, specifically the optic nerves and spinal cord.

REFERENCE
1. Highlights of Prescribing Information. Alexion. https://alexion.us/-/media/alexion_global/documents/regulatory/north-america/usa/2024/english/soliris_uspi.pdf