UCB Reports Positive Results from Phase 3 Study of Zilucoplan in Myasthenia Gravis

Global biopharma UCB reported positive topline results from the RAISE trial evaluating its experimental treatment zilucoplan, a self-administered, subcutaneous peptide inhibitor of complement component 5, versus placebo in adults with generalized myasthenia gravis (gMG).

Photo: Iris Loew-Friedrich, executive vice president and chief medical officer of UCB.

Generalized Myasthenia Gravis (gMG) is a rare, chronic and unpredictable autoimmune disease in which pathogenic autoantibodies can inhibit synaptic transmission at the neuro-muscular junction by targeting specific proteins on the post-synaptic membrane. This disrupts the ability of the nerves to stimulate the muscle and results in a weaker contraction, leading to a variety of symptoms, including drooping eyelids, double vision, and difficulty swallowing, chewing and talking, as well as severe life- threatening weakness of the muscles of respiration. gMG can occur at any age and in any race, although previous studies have shown that women are more often impacted than men. Complement activation, a key mediator of antibody function, is recognized as an important driver of pathology in gMG.

The primary endpoint of the RAISE trial was met with a clinically meaningful and statistically significant improvement from baseline in Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 12 observed for the zilucoplan treatment group vs placebo.

All key secondary endpoints were also met, including statistically significant improvements from baseline in Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Composite (MGC) score and MG-QoL15r score at Week 12 for the zilucoplan treatment group vs placebo.

The results show zilucoplan was well-tolerated and no major unexpected safety findings were identified compared to earlier zilucoplan studies. The incidence of serious treatment emergent adverse events (TEAEs) in the zilucoplan and placebo treatment arms was similar.

“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, executive vice president and chief medical officer of UCB.

Based on these results, UCB plans to progress with regulatory filings for zilucoplan in gMG in the United States, European Union, and Japan beginning later this year.

The phase 3 RAISE study is a multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, and tolerability of zilucoplan in adult patients with gMG. Patients were randomized in a 1:1 ratio to receive daily subcutaneous (SC) doses of zilucoplan or placebo for 12 weeks. The study was designed to determine if complete complement inhibition can bring clinical benefit to people with gMG and if complement inhibition was effective across a broad spectrum of patients with acetylcholine receptor antibody positive (AChR Ab+) MG regardless of disease duration, prior treatment, or response to previous therapies.

The primary endpoint for the RAISE study is change from baseline at Week 12 in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) score, an eight-item patient-reported scale developed to assess MG symptoms and their effects on daily activities. Secondary endpoints include change in the Quantitative Myasthenia Gravis (QMG) score, the Myasthenia Gravis Composite (MGC) and the Myasthenia Gravis Quality of Life 15 revised (MG-QoL15r) from baseline to Week 12; time to rescue therapy; the percentage with minimum symptom expression (MSE) (defined as MG-ADL of 0 or 1), the percentage with a ≥3-point reduction in MG-ADL and the percentage with a ≥5-point reduction in QMG, all measured at Week 12.

The findings from RAISE build on the positive results from the phase 3 MycarinG study evaluating UCB’s investigational treatment rozanolixizumab, an SC-infused monoclonal antibody targeting the neonatal Fc receptor (FcRn) which also met its primary and secondary endpoints with statistical significance in gMG.

UCB is currently the only company investigating two potential treatments with different mechanisms of action in gMG. Detailed results from both Phase 3 trials will be presented at forthcoming medical meetings in 2022.

Author: Rare Daily Staff