SMC OKs First C5 Inhibitor for Refractory Myasthenia Gravis

The Scottish Medicines Consortium (SMC) has accepted zilucoplan (Zilbrysq, UCB Pharma Ltd) for restricted use in NHS Scotland as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. The recommendation applies to patients with refractory gMG who have not responded adequately to corticosteroids and at least two other treatments, including non-steroidal immunosuppressive therapies and rituximab, or for whom these treatments are contraindicated or not tolerated. Patients must also have uncontrolled disease, defined as a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 6 or a Quantitative Myasthenia Gravis (QMG) score of at least 12, and be considered for or receiving maintenance intravenous immunoglobulin or plasma exchange.gMG is a rare, chronic, autoimmune neuromuscular disease caused by pathogenic IgG autoantibodies that disrupt transmission at the postsynaptic membrane of the neuromuscular junction. Approximately 80% of patients with myasthenia gravis are anti-AChR antibody positive. The disease leads to debilitating muscle weakness, profound fatigue, and potentially life-threatening myasthenic crises requiring mechanical ventilation in up to 20% of individuals. Targeting the Complement Pathway Zilucoplan inhibits complement protein C5, blocking assembly of the membrane attack complex and reducing the neuromuscular junction damage that drives gMG symptoms. It is the first C5 inhibitor to be made routinely available in NHS Scotland for this indication.The drug is self-administered by subcutaneous injection once daily, with dosing based on body weight: 16.6 mg for patients weighing less than 56 kg, 23 mg for those weighing 56 kg to less than 77 kg, and 32.4 mg for those weighing 77 kg or more.RAISE Trial Shows Disease Improvement The SMC recommendation was supported by the multicentre, randomised, double-blind, phase 3 RAISE study evaluating zilucoplan against placebo over 12 weeks in adults with AChR antibody-positive gMG on stable background therapy. The primary endpoint was the change from baseline in the MG-ADL score at week 12. Zilucoplan demonstrated a statistically significant and clinically meaningful least-squares mean difference of -2.09 points compared with placebo (P <.001). Statistically significant improvements were also demonstrated across key secondary endpoints, including the QMG total score (difference, -2.94 points; P <.001). Long-term open-label extension data (RAISE-XT) demonstrated maintained efficacy through 120 weeks.Safety and Monitoring Serious adverse events occurred in 16% of patients in both groups, while treatment discontinuation because of an adverse event occurred in 4.0% and 1.9%, respectively. Common adverse events included headache, injection-site bruising, diarrhoea, injection-site pain, contusion, urinary tract infection, and increased amylase or lipase levels.Because C5 inhibition increases the risk for Neisseria infection, patients must be vaccinated against meningococcal infections at least 2 weeks before starting treatment and should receive immunisations according to current guidelines.Clinical Impact and NHS Implementation The SMC said zilucoplan addresses a significant unmet need for patients with refractory gMG who previously relied on frequent, invasive, and resource-intensive maintenance treatments such as intravenous immunoglobulin or plasma exchange. Clinical experts also highlighted the practical advantages of home subcutaneous self-administration, which could reduce reliance on hospital-based treatment. “Zilucoplan will provide a more convenient treatment option for some patients with myasthenia gravis who have not been able to get their symptoms adequately controlled with currently available treatments,” said SMC Chair Dr Rob Peel.The SMC advice applies strictly within the structure of an approved NHS Scotland Patient Access Scheme, which provides a confidential discount to deliver cost-effective outcomes for NHS Boards. Implementation will require pre-treatment meningococcal immunisation and routine clinical monitoring following treatment initiation.This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.