Background:
Ravulizumab binds with high affinity to human terminal complement protein C5, blocking its activation by complement pathway. Multicenter 26-week phase 3 study spearheaded by Alexion Pharmaceuticals, Inc. evaluated the safety and efficacy of ravulizumab in adults with anti-AChR antibody-positive gMG who were complement inhibitor therapy naïve.
Objective:
To describe a novel complement C5 inhibitor therapy for treatment of adults with anti-acetylcholine receptor antibody positive (AChR Ab+) generalized Myasthenia Gravis (gMG).
Methods:
As one of the sites enrolled in the multicenter phase 3 study (NCT03920293), Olive-View UCLA enrolled AChR Ab+ adults to receive intravenous ravulizumab infusion ( as per body weight- based on dose regimen 2400-3000mg loading dose on day 1 , followed by 3000-3600 mg every 8 weeks beginning on Day 15) or placebo for 26 weeks. The multicenter study randomized 175 patients 1:1 to one of two treatment groups: 1) ravulizumab infusion or 2) placebo infusion.
Results:
At week 26, adults treated with ravulizumab, compared to those treated with placebo, demonstrated a statistically significant improvement on the Primary Endpoint; total score on the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale. Additionally, treatment with ravulizumab resulted in a statistically significant improvement in QMG total score compared to placebo. Statistically and clinically significant improvement was observed as early as week 1 of treatment. Ravulizumab exhibited a favorable safety and tolerability profile. Common side effects noted was short episodes headache.
Conclusion:
The high degree of disease burden associated with gMG warrants the need for further treatment alternatives. Trial results revealed that the ravulizumab regimen significantly reduced gMG specific-symptoms. Ravulizumab was specifically engineered with an increased half-life relative to eculizumab. Therefore, it requires less frequent dosing (once every 8 weeks). The appeal of ravulizumab stems from its relative convenience; the regimen holds potential to increase patient satisfaction, treatment-adherence, and health outcomes.