Ranging Cycle Cadence of Rozanolixizumab Highlights Need for Individualized Treatment Approach

Author(s):

Key Takeaways

Rozanolixizumab treatment in MG patients shows individualized cycle cadences, with three identified frequency clusters: low, medium, and high.
Rozanolixizumab is well tolerated across different treatment frequency clusters, with no predictive factors for cluster assignment.
Approved in 2023, rozanolixizumab is the first therapy for anti-AChR and anti-MuSK antibody-positive MG patients.
A phase 2 trial in CIDP patients showed no significant efficacy, potentially due to high disease stability in the placebo group.

Despite balanced baseline characteristics, patients ranged from low to high number of rozanolixizumab treatment cycles, suggesting the need for a personalized approach.

Vera Bril, MD, FRCPC

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.

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