Rozanolixizumab Remains Consistently Safe, Effective for gMG

The newest data on Rozanolixizumab (Rystiggo; UCB) show that this medication approved to treat adults with a specific form of generalized myasthenia gravis (gMG) continues to produce both overall symptom relief and targeted symptom relief for those with ocular impairment. Findings from the MycarinG study (MG0003/NCT03971422) and its open-label extension MG0004 (NCT04124965) show this high-affinity humanized immunoglobulin G4 monoclonal antibody and Fc receptor blocker to be safe across various treatment cycles; well tolerated, producing primarily mild to moderate adverse events; and effective over the long term, up to week 33 of treatment.^1,2

Rozanolixizumab was first approved by the FDA in June of 2023, based on data from the MycarinG trial, to treat adult patients who have anti–acetylcholine receptor (AChR)– and anti–muscle-specific tyrosine kinase (MuSK)–positive gMG.³ It received its most recent approval from the European Union for self-administration or administration from a caregiver,⁴ based on results from the MG0020 study (NCT05681715). Administration is subcutaneous and takes approximately 15 minutes.⁵

The newest data were presented across 2 posters at the 2025 Muscular Dystrophy Association Clinical & Scientific Conference in Dallas, Texas, held March 16-19, 2025.

Weekly Administration for 6 Weeks¹

The phase 3 randomized, double-blind, placebo-controlled MycarinG study evaluated the impact of weekly rozanolixizumab injections at 7 mg/kg (n = 66) or 10 mg/kg (n = 67) or placebo (n = 67) for a 6-week cycle, followed by 8 weeks of observation. This post hoc analysis of ocular-related outcomes considered changes from baseline (CFB) to day 43 in Myasthenia Gravis Activities of Daily Living (MG-ADL), quantitative MG (QMG), MG Impairment Index (MGII), and MG symptoms patient-reported outcomes (ocular muscle weakness). Lower scores on these scales indicate less disease severity.

Ocular subdomains evaluated through the scales were severity, timing/duration, time to fatigability, frequency of diplopia and ptosis, and severity of blurry vision and difficulty moving eyes side to side and up and down. Past research also shows that ocular symptoms may respond differently to treatment vs generalized symptoms.^6-8 The study authors highlighted the substantial burden that ocular symptoms place on patients who have gMG, in relation to their quality of life and ability to perform daily activities.

Across the 3 cohorts, at baseline, the mean (SD) patient age was 51.8 (16.3) years; disease duration, 8.6 (8.7) years; MG-ADL score, 8.3 (3.4); MG-ADL ocular score, 2.7 (1.7); and QMG score, 15.6 (3.6). Most patients were female and had Myasthenia Gravis Foundation of America class III disease.

Those who received rozanolixizumab demonstrated greater mean improvements vs the placebo-treated group:

• MG-ADL ocular: the 7-mg/kg group saw a 0.8-point drop and the 10-mg/kg group a 1.0-point drop vs 0.1 seen in the placebo group
• MG-ADL total score: both groups saw a 3.2-point drop vs 0.7, respectively
• QMG ocular: 1.1- and 1.7-point drops vs 0.2
• QMG total score: 4.2- and 5.6-point drops vs 0.9
• MGII ocular: 2.9- and 5.2-point drops vs 1.0
• MGII total score: 12.4- and 16.1-point drops vs 3.4

Rozanolixizumab (Rystiggo; UCB) is a high-affinity humanized immunoglobulin G4 monoclonal antibody and Fc receptor blocker approved to treat anti–acetylcholine receptor– and anti–muscle-specific kinase–positive generalized myasthenia gravis in adult patients. | Image Credit: © UCB

The placebo group also had the highest rate of adverse events, at 82.6% vs 67.2% in the 7-mg/kg and 81.3% in the 10-mg/kg rozanolixizumab groups.

Administration for 52 Weeks²

The phase 3, multicenter, randomized, placebo-controlled MG0004 study rerandomized participants from MG0003 1:1 to up to 52 weeks of weekly rozanolixizumab injections at 7 (n = 35) or 10 mg/kg (n = 35). These patients were allowed to enroll in this open-label extension study if they completed MycarinG or required rescue therapy during that trial (administered via intravenous immunoglobulin or plasma exchange). There again was an 8-week observation period after the treatment period, and patients could cross over to yet another open-label extension (MG0007; NCT04650854) after at least 6 treatment visits. The primary outcomes of interest were the safety and efficacy of chronic weekly rozanolixizumab.

The mean patient age was 52.2 (15.8) years, and most patients were female (53.5%), from Europe (50.7%) or North America (38%), and self-reported a White (50.7%) race. At baseline, mean measures were as follows: overall MG-ADL score, 8.4 (3.6); QMG score, 15.3 (5.3); and disease duration, 8.5 (9.0) years. For prior gMG medication, 84.5% reported parasympathomimetics; 62%, corticosteroids; and 52.1%, immunosuppressants. Being positive for anti-AChR antibodies was far more common vs exhibiting positivity for anti-MuSK antibodies: 87.3% vs 12.7%.

Overall, the mean treatment durations and total infusions were close to equal: 22.9 (14.6) weeks and 21.7 (13.0) infusions in the 7-mg/kg group and 23.7 (14.6) and 21.6 (12.3), respectively, in the 10-mg/kg group. Eleven percent of patients completed 52 weeks of weekly treatment, and for those who switched doses during the study (at investigator discretion), 3 of 5 who switched to 10 mg/kg and 12 of 14 who switched to 7 mg/kg stayed on those doses.

Any treatment-emergent adverse events (TEAEs) were reported in 85.7%, with the 3 most common being headache, diarrhea, and decreased immunoglobulin G (35.7%, 18.6%, and 15.7%, respectively). Serious TEAEs were reported by just 12.9%, and only 5.7% and 4.3% required permanent discontinuation from the study or the study drug, respectively, because of TEAEs. There was also a very low rate of TEAEs requiring a dose change, 1.4%. Infections were seen in 26% of the 7-mg/kg group and 21.4% of the 10-mg/kg group, but no serious, severe, or opportunistic infections.

No patient deaths were reported, and only those in the 7-mg/g group received rescue therapy (all received intravenous immunoglobulin).

Following treatment initiation, the first assessment was at week 5, with notable changes of –2.7 and –3.2 in MG-ADL score for the 7- and 10-mg/kg groups, respectively. These CFB remained stable through week 33 and were consistently higher in the higher- vs the lower-dose group. By week 33, the greatest reductions seen were –3.1 in the 7-mg/kg group and –4.1 in the 10-mg/kg group, achieved at week 14 and week 21, respectively. Median max deductions in total immunoglobulin G from baseline were 75.6% and 79.9%.

When CFB in MG composite and QMG were evaluated, the mean differences for both were –5 and –2 in the 7- and 10-mg/kg groups, respectively, from mean baseline MG composite scores of 15.0 (7.3) and 15.8 (7.5) and mean QMG scores of 15.2 (5.1) and 15.3 (5.6).

References

1. Habib AA, Pascuzzi RM, Vissing J, et al. Ocular symptoms in patients with generalized myasthenia gravis receiving rozanolixizumab: post hoc analysis of MycarinG. Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, Texas. Poster 353.

2. Bril V, Drużdż A, Grosskreutz J, et al. Safety and efficacy of chronic weekly rozanolixizumab treatment in patients with generalized myasthenia gravis (MG0004). Presented at: 2025 MDA Clinical & Scientific Conference; March 16-18, 2025; Dallas, Texas. Poster 352.

3. Joszt L. FDA Approves rozanolixizumab-noli for generalized myasthenia gravis. AJMC^®. June 27, 2023. Accessed March 21, 2025. https://www.ajmc.com/view/fda-approves-rozanolixizumab-noli-for-generalized-myasthenia-gravis

4. Rystiggo (rozanolixizumab, for generalized myasthenia gravis (gMG), received EU approval for 2 new administration methods. News release. UCB; January 31, 2025. Accessed March 21, 2025. https://www.ucb.com/newsroom/press-releases/article/rystiggorvrozanolixizumab-for-generalized-myasthenia-gravis-gmg-receives-eu-approval-for-two-new-administration-methods

5. Rystiggo. Prescribing information. UCB; 2024. Accessed March 21, 2025. https://www.rystiggo.com/

6. Meisel A, Saccà F, Spillane J, Vissing J; MG Collegium Sub-committee. Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis. Eur J Neurol. 2024;31(7):e16280. doi:10.1111/ene.16280

7. Akaishi T, Suzuki Y, Imai T, et al. Response to treatment of myasthenia gravis according to clinical subtype. BMC Neurol. 2016;16(1):225. doi:10.1186/s12883-016-0756-3

8. Barnett C, Bril V, Kapral M, Kulkarni A, Davis AM. Myasthenia Gravis Impairment Index: responsiveness, meaningful change, and relative efficiency Neurology. 2017;89(23):2357-2364. doi:10.1212/WNL.0000000000004676