Efficacy of Rozanolixizumab Seen Across Several Subgroups of Myasthenia Gravis

Tuan Hoang Vu, MD

Findings from subgroup analyses of the phase 3 MycarinG study (NCT03971422) showed that rozanolixizumab (UCB Pharma), a potential treatment for adults with generalized myasthenia gravis (gMG), was effective across a broad range of patients, regardless of prior therapy use and disease duration.¹

These data were presented by Tuan Hoang Vu, MD, neurologist, USF Health, at the 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts. The study recruited 200 adults with generalized MG who were anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive and were thus randomly assigned 1:1:1 to weekly subcutaneous rozanolixizumab 7 mg/kg (n = 66), 10 mg/kg (n = 67), or placebo (n = 67) for 6 weeks.

The post-hoc subgroup analyses included number of prior MG therapies—excluding acetylcholinesterase inhibitors—baseline disease severity, and disease duration. At the end of the 43-day treatment observation period, investigators observed least square mean (LSM) changes of –3.2, –3.3, and –1.0 in Myasthenia Gravis–Activities of Daily Living (MG-ADL), the primary end point, for patients with at least 1 prior MG therapy on rozanolixizumab 7 mg/kg, 10 mg/kg, and placebo groups, respectively. For those on at least 2 prior MG therapies, mean observed change from baseline in MG-ADL was –2.5, –3.0, and –0.8, in the respective groups.

A treatment response was considered an improvement of at least 2 points on MG-ADL, and 3-point improvement on both Quantitative Myasthenia Gravis (QMG) and Myasthenia Gravis Composite (MGC) scores. In the rozanolixizumab 7 mg/kg, 10 mg/kg, and placebo groups, for those with QMG scores less than 15, mean observed changes from baseline in MG-ADL were −3.7, −2.6, and −0.6, respectively. For those with QMG scores greater than 15, the mean observed changes from baseline were −3.0, −4.0, and −0.7.

In a subgroup of patients with disease duration of less than 4 years, investigators observed LSM changes in MG-ADL at day 43 of –2.9, –3.1, and –0.6 in the rozanolixizumab 7 mg/kg, 10 mg/kg, and placebo groups, respectively. For those with longer disease duration, those in the rozanolixizumab 7 mg/kg and 10 mg/kg groups recorded changes of –3.8 and –3.3, respectively, compared with changes of –0.7 for those on placebo. In terms of safety, treatment-emergent adverse events (TEAEs) occurred in 81.3% (n = 52) of patients in the rozanolixizumab 10 mg/kg group, 82.6% (n = 57) in the 7 mg/kg group, and 67.2% (n = 45) of those on placebo.

Earlier this year, in January, the FDA granted priority review for rozanolixizumab’s biologic license application, with the MycarinG study serving as the basis for the application. All told, original findings showed that those in the rozanolixizumab 7-mg/kg and 10-mg/kg groups had least-square mean changes of ­–3.370 (difference vs placebo, ­–2.586; 95% CI, –4.091 to –1.249) and –3.403 (difference vs placebo, –2.619; 95% CI, –3.994 to –1.163), respectively, on MG-ADL, compared with –0.784 for those on placebo.^2,3

Overall, rozanolixizumab-treated patients showed better response on all outcomes relative to placebo. Specifically, 71.9% and 69.4% in 7 mg/kg and 10 mg/kg groups, respectively, achieved response on MG-ADL, compared with 31.3% of those on placebo. In terms of QMG scores, 54.7%, 72.6%, and 39.1% of those in the rozanolixizumab 7-mg/kg, 10-mg/kg, and placebo groups, respectively, achieved a response. Similarly, 60.9%, 74.2%, and 40.6% of the same respective groups achieved response on MGC. Notably, only 3.0% of patients on placebo had minimal symptom expression compared with 25.8% and 28.4% of those in the 7-mg/kg and 10-mg/kg active treatment groups, respectively.

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REFERENCES
1. Vu T, Druzdz A, Habib AA, et al. Efficacy of rozanolixizumab in generalized myasthenia gravis: subgroup analyses from the randomized phase 3 MycarinG study. Presented at: 2023 AAN Annual Meeting; April 22-27; Boston, MA. Abstract 002951
2. UCB announces rozanolixizumab BLA for the treatment of generalized myasthenia gravis filed with U.S. FDA and designated for Priority Review. News Release. UCB. Accessed April 20, 2023 https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-rozanolixizumab-BLA-for-the-treatment-of-generalized-myasthenia-gravis-filed-with-US-FDA-and-designated-for-Priority-Review
3. Bril V, Druzdz A, Grosskreutz J, et al. Rozanolixizumab in generalized myasthenia gravis: responder analyses from the randomized phase 3 MycarinG study. Presented at: AANEM Annual Meeting; September 21-24; Nashville, Tennessee. Abstract 204.