Impact on fatigue
In a separate post hoc analysis of patients who entered RAISE-XT, the researchers evaluated long-term effects of zilucoplan on fatigue.
Improvements in fatigue were already apparent at the end of the RAISE trial, with the least squares mean (LSM) change from baseline in fatigue assessed after 12 weeks with the Neuro-QOL T-score being –6.26 for zilucoplan (n = 86) compared with an increase of 2.65 for placebo (n = 88; LSM difference, –3.61; nominal P = .0060).
Patients who received placebo in the RAISE trial were able to switch to zilucoplan in the RAISE-XT open-label trail, and among those who did, fatigue, as measured in the T-scores, improved significantly within 1 week of switching.
Fatigue further improved out to week 16 in terms of T-scores for the placebo-switch as well as zilucoplan groups, and the improvements in the scores were sustained through week 60 (mean change from RAISE baseline, –10.71 [n = 42] and –9.15 [n = 42], respectively).
“Fatigue is a challenge for patients with [generalized myasthenia gravis]. Zilucoplan significantly and clinically meaningfully improved myasthenic fatigue versus placebo during RAISE,” the investigators report.
“Further improvements were observed during RAISE-XT and were sustained up to 60 weeks of treatment,” they added.
Favorable safety profile
Zilucoplan continued to show a favorable safety profile in the RAISE-XT trial and was well tolerated in the long term.
The most common adverse reactions (10% or more) in patients with generalized myasthenia gravis were injection-site reactions, upper respiratory tract infection, and diarrhea.
Though additional therapies have also recently entered the market for generalized myasthenia gravis, they are either intravenous or subcutaneous infusions requiring a health care professional to administer them.
“This self-administered medication allows patients to be more independent and can even travel since it is not dependent on an infusion center,” Dr. Freimer noted.
However, similar to the other complement inhibitors, zilucoplan carries a risk for infection, particularly meningitis, Dr. Du noted. “Complement meningitis vaccination protocol and close monitoring for signs of infection are required,” she said.
However, she added, “the rapid action benefits shown as early as week 1 are impressive, and potentially open the door to use as adjunctive therapy in myasthenia gravis crisis.”
“I think zilucoplan definitely adds more excitement to the already active field of myasthenia gravis management,” she said.
The study was funded by UCB Pharma. Dr. Freimer has reports she has served as a paid consultant for argenx, UCB Pharma, and Alexion Pharmaceuticals and reports research support from the National Institutes of Health, UCB Pharma, Jansen Pharmaceuticals, Alnylam, Avidity, and Fulcrum. Dr. Du reports no disclosures.
A version of this article appeared on Medscape.com.