Rozanolixizumab Safe, Well-Tolerated in Myasthenia Gravis in Phase 3 Study

Author(s):

Statistical significance was observed for both the MycarinG study’s primary and secondary end points in a population of 200 patients with myasthenia gravis treated with the UCB agent.

Vera Bril, MD, FRCPC

Positive topline results from the phase 3 MycarinG study (NCT03971422) of rozanolixizumab, a subcutaneously infused monoclonal antibody targeting the neonatal Fc receptor, in adults with generalized myasthenia gravis (gMG) were recently announced by UCB. The trial met its primary end point in achieving a statistically significant and clinically meaningful change in the total Myasthenia Gravis-Activities of Daily Living (MG-ADL) score from baseline to day 43, when compared with placebo.¹

Secondary end points were also met with statistical significance, including response rates, changes in the Myasthenia Gravis Composite score, the Quantitative MG (QMG) score, patient-reported outcomes, and occurrence of adverse events. The treatment was found to be well-tolerated in patients, with no newly identified safety signals.

Rozanolixizumab is not currently approved for use in any indication by any regulatory authority, and safety and efficacy have not been established by the FDA. The final data from the phase 3 study are anticipated to be presented at a medical meeting next year, with UCB expecting to move forward with regulatory filings in the US, the European Union, and Japan in Q3 2022.

“Today’s encouraging findings from the MycarinG study show the potential of rozanolixizumab in the treatment of MG, and further reinforce the suggestion that FcRn [human neonatal Fc receptor] inhibition may be a promising approach for this disease,” lead investigator Vera Bril, MD, FRCPC, professor of medicine/neurology, University of Toronto; and director, Neuromuscular Section, division of neurology, University of Toronto and University Health Network, Toronto, Canada, said in a statement.¹

The double-blind, placebo-controlled study enrolled 200 participants with gMG who were then randomized to 1 of 2 treatment arms or placebo. Rozanolixizumab is also being developed for other pathogenic immunoglobulin-autoantibody-drive autoimmune diseases, namely primary immune thrombocytopenia, myelin oligodendrocyte glycoprotein antibody-associated disease, and auto immune encephalitis.

“We are enthusiastic about these positive and clinically meaningful results, which mark a critical step forward for rozanolixizumab and UCB’s commitment to delivering differentiated solutions for people living with rare diseases, such as MG,” Iris Loew-Friedrich, MD, PhD, executive vice president and chief medical officer, UCB, said in a statement.1 “In line with our ambition to deliver a portfolio of treatment options which could improve and simplify the treatment experience for patients and physicians, we are committed to bringing transformational outcomes and experiences to those in need. We wholeheartedly thank the MG community for their ongoing partnership and participation in this study.”

Also being investigated by UCB is its developmental medicine zilucoplan, a peptide inhibitor of complement component 5. Preliminary results from the phase 3 RAISE study (NCT04115293), evaluating safety, efficacy, and tolerability treatment in patients with gMG, are anticipated to be announced in the coming weeks.

A phase 2a multicenter trial (NCT03052751) of rozanolixizumab was previously conducted in patients with gMG. While changes in QMG scores were insignificant during this phase of study, the treatment was well-tolerated, indicating the potential clinical benefit.2 Investigators found that least square (LS) mean change from baseline to day 29 on QMG score for those who received rozanolixizumab was –1.8, compared with –1.2 for those on placebo (difference, –0.7 [95% upper confidence level (UCL), 0.8]; P = 0.221). Despite improvements, these were statistically insignificant.²

Improved day-to-day function, as measured by change from baseline to day 29 in MG-ADL was observed following treatment with rozanolixizumab compared with placebo (LS mean, –1.8 vs –0.4; difference, –1.4 [95% UCL, –0.4]). MG-Composite scores for those who were administered the agent also showed changes from baseline to day 29 compared with placebo (LS mean, –3.1 vs –1.2; difference, –1.8 [95% UCL, 0.4]).

REFERENCES

1. UCB announces positive phase 3 results for rozanolixizumab in generalized myasthenia gravis. News release. UCB. December 10, 2021. Accessed December 10, 2021. https://www.ucb-usa.com/stories-media/UCB-U-S-News/detail/article/ucb-announces-positive-phase-3-results-rozanolixizumab
2. Bril V, Benatar M, Anderson H, et al. Efficacy and safety of rozanolixizumab in moderate-to-severe generalized myasthenia gravis. Neurology. 2021;96(6):e853-e865. doi:10.1212/WNL.0000000000011108