Ericka Wong, MD: Eculizumab is a humanized monoclonal antibody that’s directed against the C5 complement. It’s binding to the C5 complement prevents its cleavage into the active component- C5a and C5b, and this prevents the formation and deposition of the membrane attack complex which ultimately aids in the destruction and eventual simplification of the neuromuscular junction. In the phase 3 multicenter REGAIN trial [NCT02507505], eculizumab was studied in acetylcholine receptor antibody-positive patients with myasthenia gravis [MG}, who were considered refractory to prior treatment. Even though the primary efficacy endpoint of improving the MG-ADL [Myasthenia Gravis Activities Of Daily Living Scale] score was not statistically significant, several secondary end points showed there was meaningful clinical response. Improvement of quality of life, activities of daily living, its clinical response to treatment was sustained throughout the trial at 26 weeks, and then the majority of them also had the sustained effect through the open-label extension.

Due to the increased risk of meningococcal infections with complement inhibitors, patients are required to be vaccinated before the medication is administered. During the REGAIN trial, patients were required to be vaccinated. There were no cases of meningococcal infections that occurred. There were also no serious infections or safety concerns. The most common adverse effects were headache, URI [upper respiratory infection], and nasopharyngitis.

In terms of patient selection, patients that were studied in the trial were refractory meaning that they were treated with at least 2 immunosuppressive therapies or they were on 1 immunosuppressive therapy and on chronic IVIG [intravenous immunoglobulin] and plasma exchange [PLEX] for 12 months without symptom control. It is the first complement inhibitor that was introduced for myasthenic patients, so it really did change how we think about treating our patients with targeted therapy.

Because of eculizumab’s novel mechanism, by acting on the complement, it really is limited to acetylcholine receptor antibody positive myasthenia patients. And because the trial really looked at patients who are refractory, this is a medication that I consider for myasthenic patients who I consider refractory. As with the prior definition of failing 2 chronic immunosuppressants or 1 immunosuppressant with IVIG and PLEX. Other considerations are the high cost of the complement inhibitors and getting approval by insurance companies. That is something that we certainly need to consider. Also, eculizumab needs to be given every 2 weeks so that is something that sometimes the patients will need to work into their lifestyle. It’s yet to be seen if this can be a tolerated long-term therapy.

Transcript Edited for Clarity