Novel Complement Inhibitor Ravulizumab Receives FDA Approval for the Treatment of generalized Myasthenia Gravis


Clinical Trials

Poster Number: M262


Shaweta Khosa, MD, Olive View-UCLA Medical Center, Namrata Shetty, BS, University of California, San Francisco, Gurveer Khosa, MBBS, Adesh Institute of Medical Sciences & Research, Shri Kant Mishra, MD, Olive View-UCLA Medical Center, Robert Freundlich, MD, Olive View-UCLA Medical Center

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.

To describe a novel complement C5 inhibitor therapy for treatment of adults with anti-acetylcholine receptor antibody positive (AChR Ab+) generalized Myasthenia Gravis (gMG).

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.

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.

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.