| Muscle & Neuromuscular Junction Disorders | Rare Neurological Diseases  

Zilucoplan shows long term efficacy in Myasthenia gravis

An interim analysis of the phase 3 open-label extension study (RAISE-XT) testing zilucoplan (a self-administered subcutaneous complement C5 inhibitor) on myasthenia gravis patients, showed interesting results both on safety profile and in term of efficacy. Indeed, significant clinical improvements was observed in patients continuing their zilucoplan from the double-blind period as well as in patients who switched to zilucoplan from placebo.

Zilucoplan (UCB) is a self-administered subcutaneous complement C5 inhibitor.

The RAISE trial demonstrated that 0.3 mg/kg daily of zilucoplan significantly reduced the MG-ADL, qMG score, Myasthenia Gravis Composite (MGC), and Myasthenia Gravis Quality of Life 15-item Scale score relative to placebo at week 12. Based on these results, Zilucoplan was accepted by the FDA in November 2022, and is currently in early access programme in some European countries.

More recently, an interim analysis of the phase 3 open-label extension study (RAISE-XT), showed interesting results both on safety profile and in term of efficacy. Indeed data from 199 patients coming from the previously conduced phase 2 (NCT03315130) and phase 3 (NCT04115293) studies were analysed. These patients either were continuing their zilucoplan treatment from the double-blind period or switched to zilucoplan from placebo.

After 24-month of treatment, the safety data showed the following results:

* 84.9% reported treatment-emergent adverse events (TEAEs). The most common TEAEs being headache and worsening of MG in 16.6% of patients.

* 23.1% documented serious AEs.

* 49.2% reported infections, but most of them (86%) were mild.

In term of efficacy, both zilucoplan-treated individuals and patients who switched achieved least square mean (LSM) changes in MG-ADL score of approximately –6.30. Finally, results of qMG, Myasthenia Gravis Composite score (MGC), and Myasthenia Gravis Quality of Life 15-item-revised, were also improved similarly across both treatment groups as well.

Key Points:

  • Zilucoplan (UCB) is a self-administered subcutaneous complement C5 inhibitor.
  • Zilucoplan is safe based on the results of the phase 3 open-label extension study (RAISE-XT)
  • Both zilucoplan-treated individuals and patients who switched from the placebo group showed clinical meaningful improvement

References:

  1. Genge A, Hussain Y, Kaminski HJ, et al. Safety and tolerability of zilucoplan in RAISE-XT: a multicenter, open-label extension study in patients with myasthenia gravis. MDA 2023. Abstract 145.

Publish on behalf of the Scientific Panel on Muscle and NMJ disorders

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