Zilucoplan Safely Reduced gMG Symptoms in Phase 3 Trial

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Zilucoplan, UCB’s experimental therapy, safely and effectively eases symptom severity and improves the quality of life for adults with generalized myasthenia gravis (gMG), while helping them complete daily activities, according to top-line data from the Phase 3 RAISE clinical trial.

Based on these findings, indicating the trial met its main and secondary goals, UCB plans to submit applications to regulatory agencies in the U.S., Europe, and Japan, later this year seeking the therapy’s approval for adults with gMG.

“While there has been recent progress in the treatment of MG, there is still a significant unmet need for new, effective treatment options that address the unpredictable, fluctuating symptoms of MG — some of which require urgent treatment or hospitalization — to improve patient outcomes and quality of life,” Raquel Pardo, president of the Spanish Myasthenia Association, said in a press release.

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“These exciting results give us additional reason to believe that zilucoplan can offer an important step forward in addressing the unmet needs of people living with gMG,” said James F. Howard, MD, the trial’s lead investigator at the University of North Carolina School of Medicine, where he is a professor of neuromuscular disease, and chief of the neuromuscular disorders section.

“As we strive to improve the management of this complex and unpredictable disease, any new medicines will be welcomed by physicians to help us realize our goal of offering effective and flexible treatment approaches in gMG which are tailored to the needs of individual patients,” Howard added.

Notably, these promising findings come on the heels of similar, positive Phase 3 trial results of UCB’s other investigational therapy for adults with gMG, rozanolixizumab, showing the therapy significantly eased symptom severity and reduced their impact on daily activities.

UBC expects to present detailed results from both Phase 3 trials at upcoming medical meetings.

“Positive results for zilucoplan and rozanolixizumab — each with a different mechanism of action — bring us one step closer to achieving our ambition of delivering choice and flexibility for a broad range of patients and physicians at each step of their treatment journey, addressing significant unmet needs and offering unique patient value,” said Iris Loew-Friedrich, MD, PhD, UCB’s executive vice-president and chief medical officer.

“We thank the MG community for their continued insights, partnership and participation in this study,” Loew-Friedrich added.

Zilucoplan, originally developed by Ra Pharma, now part of UCB, is a small molecule that specifically blocks the C5 protein. C5 plays a role in the complement system, a part of the immune system that is involved in the damaging immune responses that drive MG.

By reducing inflammation and abnormal immune responses, the therapy, administered through under-the-skin injections, is expected to help ease symptoms and improve the quality of life of people with MG.

Zilucoplan received orphan drug designation in the U.S. for MG, which is meant to help accelerate the therapy’s clinical development and regulatory review.

The international Phase 3 RAISE trial (NCT04115293), which began dosing in 2019, evaluated the safety, tolerability, and effectiveness of zilucoplan against a placebo in 174 adults, ages 18–74, with gMG. All were positive for antibodies against the acetylcholine receptor, the most common type of MG-causing antibody.

Participants were assigned randomly to self-administer, at home, daily under-the-skin injections of either zilucoplan (0.3 mg/kg) or a placebo for 12 weeks (about three months).

Top-line results showed the trial met its main goal, with zilucoplan being superior to a placebo at reducing symptom severity and their impact on patients’ daily activities, as assessed with the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale.

Zilucoplan-treated patients also showed significant reductions in other validated measures of symptom severity, including the Quantitative Myasthenia Gravis score and the Myasthenia Gravis Composite score, relative to those on a placebo.

Compared with a placebo, the experimental therapy also was associated with a significant improvement in patients’ quality of life, as assessed with the Myasthenia Gravis Quality of Life 15 revised.

Zilucoplan was generally well-tolerated, with no new major safety concerns identified relative to previous trials, and with the rates of adverse side effects being similar to those seen with the placebo.

These findings highlighted the trial met both its main and secondary goals, pointing to Zilucoplan as a potential, effective treatment for adults with gMG.

Patients who completed RAISE were given the opportunity to enroll in an open-label extension study, called RAISE-XT (NCT04225871), in which all are receiving the experimental therapy for a longer period. The study is expected to conclude in May 2024.

UCB also is evaluating zilucoplan as a potential treatment for amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease in which the complement system has been shown to be activated abnormally.