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

Tuan Vu, MD

(Credit: LinkedIn)

Findings from a new post-hoc analysis of the phase 3 MycarinG (NCT03971422) study showed that rozanolixizumab (Rystiggo; UCB Pharma), an FDA-approved therapy, displayed efficacy and was well-tolerated among patients with generalized myasthenia gravis (gMG) aged at least 65 years, an often underrepresented patient population in clinical studies.¹

During the trial, a total of 200 participants with gMG received placebo treatment (less than 65 years, n = 51; at least 65 years, n = 16) or rozanolixizumab therapy (less than 65 years, n = 100; at least 65 years, n = 33). Presented at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) meeting, held October 15-18, in Savannah, Georgia, the mean standard deviation change from baseline to day 43 in Myasthenia Activities of Daily Living (MG-ADL) scores was −1.1 (SD, 2.7) and −3.7 (SD, 3.2) for placebo- and rozanolixizumab-treated patients aged less than 65 years. For context, the mean standard deviation was 0.7 (SD, 2.8) and −2.1 (SD, 4.0) for placebo- and rozanolixizumab-treated patients aged at least 65 years, respectively.

MycarinG randomized 1:1:1 adults with acetylcholine receptor or muscle-specific tyrosine kinase autoantibody-positive gMG aged at least 65 years to either weekly subcutaneous placebo rozanolixizumab 7mg/kg or rozanolixizumab 10mg/kg for 6 weeks. Conducted by lead author Tuan Vu, MD, professor of neurology at University of South Florida, and colleagues, the primary end point was change from baseline to day 43 on the MG-ADL score. In this post hoc analysis, investigators also analyzed baseline characteristics and incidence of treatment-emergent adverse events (TEAEs) by age.

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All told, the baseline characteristics were broadly similar between subgroups. Authors also noted that 98.0% (n = 148) of patients aged less than 65 years and all patients aged at least 65 years used concomitant medications. Additionally, researchers reported that comorbidities, such as cardiac and vascular disorders, were generally more common among the older subgroup in comparison with the younger subgroup.

Researchers reported that TEAEs occurred in 60.8% (n = 31) and 85.0% (n = 85) of placebo- and rozanolixizumab-treated patients aged less than 65 years, respectively, and in 87.5% (n = 14) and 72.7% (n = 24) of patients aged at least 65 years. The most common TEAE was headache, which was the most common among the younger subgroup (placebo, n = 11; rozanolixizumab, n = 49) compared with the older subgroup (placebo, n = 2; rozanolixizumab, n = 6).

Presented at 2023 American Academy of Neurology (AAN) Annual Meeting, held April 22-27, in Boston, Massachusetts, findings from subgroup analyses of the MycarinG study showed that rozanolixizumab was effective across a broad range of patients with gMG, regardless of prior therapy use and disease duration.² 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 MG-ADL 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, 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.

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REFERENCES
1. Vu T, Habib AA, Pascuzzi RM, et al. Rozanolixizumab in Patients Aged ≥65 Years With Generalized Myasthenia Gravis: A Post Hoc Analysis of the Phase 3 MycarinG Study. Presented at: 2024 AANEM; October 15-18; Savannah, Georgia. Abstract 200.
2. 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