Findings in UCB’s Myasthenia Gravis Pivotal Trials Detailed
Phase 3 zilucoplan and rozanolixizumab studies in generalized MG patients
Two investigational UCB treatments for generalized myasthenia gravis (gMG) — zilucoplan and rozanolixizumab — continue to show benefits in gMG patients, according to recently reported findings from Phase 3 trials.
Both delivered as subcutaneous (under-the-skin) injections, zilucoplan works by blocking an immune system protein called C5 that has been implicated in driving MG, while rozanolixizumab works by reducing the time that MG-causing antibodies spend circulating in the bloodstream.
Detailed data from the two clinical programs were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) annual meeting held Sept. 21–24, in Nashville, Tennessee. Oral and poster presentation abstracts are available.
“Patients living with gMG experience high disease and treatment burden resulting in a significant impact on their daily lives,” Iris Loew-Friedrich, executive vice president and chief medical officer at UCB, said in a company press release.
“The data being presented … reinforce the potential of UCB’s two investigational medicines with different mechanisms of action to provide targeted treatment options to patients,” Loew-Friedrich added.
Findings in RAISE Phase 3 trial of zilucoplan
The international Phase 3 RAISE trial (NCT04115293) assessed zilucoplan’s safety and effectiveness in adults with gMG carrying antibodies against the acetylcholine receptor (AChR) — the most common type of MG-causing antibody. A total of 174 participants self-administered zilucoplan (0.3 mg/kg) or a placebo, daily, for three months.
Study findings were presented in an oral presentation titled, “Quality of Life Outcomes in RAISE: A Double-Blind, Randomized, Placebo-Controlled Study Of Zilucoplan In GMG” and in the poster “Efficacy and Safety of Zilucoplan In Myasthenia Gravis: Responder Analysis From The Randomized Phase 3 RAISE Trial.”
The trial’s main goal was to assess changes in MG activities of daily living (MG-ADL) scores, a measure of disease severity, from the study’s start to week 12.
Previously reported top-line data showed that zilucoplan was superior to a placebo at easing gMG symptom severity and improving patients’ quality of life. Zilucoplan led to significant improvements in MG-ADL scores at week 12, newly reported to be 2.09 points lower in treated patients than in the placebo group.
More patients receiving zilucoplan achieved a clinically meaningful reduction of at least three points in MG-ADL scores (73.1% vs. 46.1%) and at least a five-point reduction in quantitative MG (QMG) scores (58% vs. 33.3%), another measure of disease severity, compared with the placebo group. Treated participants also showed consistently greater improvements in quality of life and fatigue compared with placebo, and fewer work impairments, the recent analyses reported.
Zilucoplan also had a favorable safety profile, with the most common treatment-emergent adverse events being mild injection site reactions, as previously reported.
All patients in the zilucoplan arm who completed RAISE have entered the ongoing RAISE-XT extension study (NCT04225871). RAISE-XT includes gMG patients with AChR antibodies who previously participated in RAISE or the 12-week, placebo-controlled Phase 2 trial (NCT03315130) of zilucoplan.
All participants are receiving the investigational treatment in the extension study.
In the poster titled, “Safety and Tolerability of Zilucoplan In RAISE-XT: A Multicenter, Open-Label Extension Study In Patients With Myasthenia Gravis,” interim analyses from RAISE-XT, with a data cutoff of Feb. 18, were presented.
Consistent with findings from both prior studies, zilucoplan demonstrated a favorable long-term safety profile over 24 weeks, or about six months, with no major safety findings.
Twelve weeks into the extension study, or after 24 weeks of treatment in total, patients previously in the zilucoplan arm saw a mean drop in MG-ADL scores of 6.3 points, demonstrating a clinical improvement. Similarly, patients who switched from a placebo in the main trial to zilucoplan experienced a 6.32 decline in MG-ADL scores after 12 weeks of treatment.
Findings in MycaringG Phase 3 trial of rozanolixizumab
UCB also presented findings from its rozanolixizumab clinical program.
The Phase 3 MycarinG study (NCT03971422) evaluated the efficacy of this investigational treatment in patients with AChR or muscle specific kinase (MuSK) antibodies, a more rare MG-causing antibody. MuSKs usually cause a more severe and harder-to-treat disease.
In the trial, 200 gMG adults were randomly assigned to weekly injections of rozanolixizumab (7 or 10 mg/kg) or a placebo for six weeks.
UCB reported findings from MycarinG in two poster presentations: “Rozanolixizumab in Generalized Myasthenia Gravis: Responder Analyses From the Randomized Phase 3 MycarinG Study” and “Efficacy of Rozanolixizumab In Muscle Specific Kinase Antibody-Positive Generalized Myasthenia Gravis: Outcomes From The Randomized, Phase 3 MycarinG Study.”
Results showed that either dose of rozanolixizumab was superior to a placebo at reducing MG-ADL scores, easing symptom severity as previously reported.
Notably, in the MuSK antibody subgroup, MG-ADL scores dropped by 7.28 points (7 mg/kg) or 4.16 points (10 mg/kg), while they increased (worsened) by 2.28 points in the placebo group. Improvements were also seen in the AChR antibody subgroup.
A greater percentage of patients in the rozanolixizumab treatment arms achieved a two-point or greater reduction in MG-ADL, and a three-point or greater reduction in QMG compared with the placebo group. The treatment was generally safe and well-tolerated.
In the oral presentation “Safety and Tolerability of Rozanolixizumab In The Randomized Phase-3 MycarinG Study,” UCB expanded on these safety findings, showing that the investigational treatment was generally well-tolerated, with most adverse events being mild or moderate in severity. Side effects were more common in the rozanolixizumab group, with the most frequently reported being headache, diarrhea, fever, and nausea.
An open-label extension study (NCT04650854) is evaluating the treatment’s long-term safety and effectiveness in patients who completed previous rozanolixizumab trials.
“We are committed to meeting patients’ needs, regardless of antibody profile, including those with MuSK Ab+ gMG who have particularly limited treatment options,” Loew-Friedrich said. “With our gMG pipeline, we hope to address both drivers of disease pathology and which account for approximately 95% of patients living with gMG.”