Ranging Cycle Cadence of Rozanolixizumab Highlights Need for Individualized Treatment Approach

A clustering analysis of the phase 3 MycarinG study (NCT03971422) and its open-label extension (OLE), MG0007 (NCT04650854), showcased the variety in cycle cadences for patients with myasthenia gravis (MG) treated with rozanolixizumab (Rystiggo; UCB). Overall, this analysis suggested that each patient takes an individualized approach to rozanolixizumab treatment based on their own disease experience, as the study included a broad, adult population.¹

In MyCarinG, the study that led to rozanolixizumab’s approval, adults with generalized MG received one 6-week rozanolixizumab treatment cycle, followed by an observation period for 8 weeks. Led by Vera Bril, MD, FRCPC, professor of medicine/neurology, University of Toronto; and director, Neuromuscular Section, University of Toronto, all patients who entered the OLE received 1 further treatment cycle with subsequent need-based cycles initiated at the investigator’s discretion.

Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, the clustering analysis included those who had at least 1 treatment cycle from MycarinG and MG0007. Results showed that the most balanced clustering and optimal goodness-of-fit was achieved using 3 clusters to describe number of cycles per year. These included low (<2.59), medium (2.59-4.64), and high (>4.64).

In the analysis, data revealed that the mean number of cycles per year in each cluster was 1.50 (0.53; n = 74), 3.59 (0.60; n = 60), and 5.82 (0.72; n = 50), respectively. Rozanolixizumab, which works by binding to human neonatal Fc receptor (FcRN), was considered well tolerated across the 3 clusters. Furthermore, despite balanced baseline characteristics from participants, there were no factors to predict which cluster a patient would be.

READ MORE: Rozanolixizumab Efficacious in Older Patients With Generalized Myasthenia Gravis, Phase 3 Data Show

Rozanolixizumab was approved in 2023 as a treatment for generalized MG, becoming the first approved therapy for both patients who are either anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive. Data from MycarinG served as the basis for the approval. In the original study, rozanolixizumab 7-mg/kg and 10-mg/kg groups had a least-square mean change on Myasthenia Gravis-Activities of Daily Living (MG-ADL) 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) compared with –0.784 for those on placebo.^2,3

In the original trial, the most commonly reported treatment-emergent adverse events (TEAEs) were headache, diarrhea, pyrexia, and nausea. Overall, a higher proportion of TEAEs occurred in comparison with placebo (81.3% for 7 mg/kg, 82.6% for 10 mg/kg, and 67.2% for placebo), including headache.

Earlier this year, UCB announced data from a phase 2 trial (NCT03861481) assessing rozanolixizumab’s effect in patients with chronic demyelinating polyradiculoneuropathy (CIDP). Otherwise known as CIDP01, it was the longest exposure to an FcRn inhibitor in a clinical study to date. All told, the therapy did not demonstrate efficacy, as investigators observed no significant between-group differences in inflammatory Rasch-built Overall Disability Scale (iRODS) score, the primary end point (rozanolixizumab: least square mean [LSM], 2.0 [SE, 3.2] vs placebo: LSM, 3.4 [SE, 2.6]; difference, –1.5; 90% CI, –7.5 to 4.5).⁴

The study, which featured 34 patients with definite or probable CIDP, may have been impacted by the high disease stability rate in patients on placebo. Throughout the double-blind period, those on active treatment saw a reduction in IgG levels by more than 80% to a mean of approximately 2 g/L, with concentrations stabilizing by around day 36. Despite high neurofilament light chain levels observed in both groups, no clinically meaningful trends were reported following treatment.

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REFERENCES
1. Habib AA, Vu T, Utsugisawa K, et al. Rozanolixizumab treatment patterns in patients with generalized myasthenia gravis: post hoc analysis. Presented at: 2024 AANEM Annual Meeting; October 15-18; Savannah, GA.
2. UCB announces US FDA approval of Rystiggo (rozanolixizumab-noli) for the treatment of adults with generalized myasthenia gravis. News release. June 27, 2023. Accessed October 16, 2024. https://www.prnewswire.com/news-releases/ucb-announces-us-fda-approval-of-rystiggo-rozanolixizumab-noli-for-the-treatment-of-adults-with-generalized-myasthenia-gravis-301864023.html
3. Bril V, Druzdz A, Grosskreutz J, et al. Safety and efficacy of rozanolixizumab in patients with generalized myasthenia gravis (MycarinG): a randomized, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-394. doi:10.1016/S1474-4422(23)00077-7.
4. Querol L, De Seze J, Dysgaard T, et al. Efficacy, safety, and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomized, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study. Neurol, Neurosurg & Psych. Published online May 10, 2024. doi:10.1136/jnnp-2023-333112