LUMINESCE: Assessing Satralizumab in Generalized Myasthenia Gravis

Even though therapeutic options for generalized myasthenia gravis (gMG) have grown in recent years, a meaningful number of patients continue to experience debilitating weakness.

The LUMINESCE phase 3 trial attempts to address this issue by testing the efficacy and safety of satralizumab, a humanized monoclonal antibody targeting the interleukin-6 (IL-6) receptor. More specifically, it aimed to assess whether upstream modulation of autoimmune pathways could alter outcomes in gMG.

Here’s a quick look at the trial and its results.

What Is IL-6?

IL-6 is a soluble cytokine with well-documented roles in autoimmunity, particularly in driving B-cell differentiation into autoantibody-producing plasma cells and skewing T-cells toward inflammatory T helper cells. This places IL-6 as a mediator in the autoimmune processes that culminate in neuromuscular junction dysfunction in gMG.

Satralizumab, already approved for aquaporin-4–positive neuromyelitis optica spectrum disorder, offers durable receptor blockade thanks to its “recycling antibody” design, extending circulation and maximizing IL-6 inhibition.

How Was LUMINESCE Designed?

The LUMINESCE trial was a randomised, double-blind, placebo-controlled, multicenter phase 3 study conducted across 105 hospitals and clinics in Europe, the Americas, Asia, and Australia.

A total of 188 patients aged 12 years and older were enrolled, all of whom were seropositive for acetylcholine receptor (AChR) (n=168), muscle-specific receptor kinase (MuSK) (n=16), or low-density lipoprotein receptor-related protein 4 (LRP4) (n=4) IgG antibodies; classified as Myasthenia Gravis Foundation of America (MGFA) class II–IV; and had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least five while on stable background therapy.

Participants were randomly assigned to receive either subcutaneous satralizumab (120 milligrams for those weighing 100 kilograms or less, and 180 milligrams for those over 100 kilograms) or placebo, administered at weeks zero, two, and four, and then every four weeks through week 24.

The primary endpoint focused on the change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 24 among AChR-IgG–positive patients.

Secondary endpoints included changes in the Quantitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL15r), Myasthenia Gravis Composite (MGC), the need for rescue therapy, and fatigue scales.

Confirmatory secondary efficacy endpoints for the overall population were changes from baseline in MG-ADL and QMG scores at week 24.

What Were the Efficacy Findings?
Looking at the results, at week 24, satralizumab demonstrated a statistically significant but modest benefit over placebo in the AChR-IgG–positive cohort.

• MG-ADL scores: −3.59 with satralizumab versus −2.57 with placebo; between-group difference −1.02 (p=0.020). 71 percent of satralizumab patients achieved ≥2-point MG-ADL reduction versus 59 percent on placebo.
• QMG scores: −3.41 with satralizumab versus −1.78 with placebo; difference −1.63 (p=0.0062). 48 percent of satralizumab patients achieved ≥3-point QMG reduction versus 29 percent on placebo.
• MG-QoL15r: no significant difference (p=0.11).
• Rescue therapy use: lower in satralizumab group (seven percent versus 14 percent), though not statistically powered.
• No conclusions were drawn from changes in MGC score or fatigue score.

Interestingly, clinical responses emerged as early as week four and were sustained through week 24, but no further meaningful gains were observed in the open-label extension period.

MuSK-IgG-positive patients treated with satralizumab had a greater change in MG-ADL score, but it was not significant. The LRP4-IgG-positive patient group was not reported.

Results from the total study population of 188 patients were not reported, although the authors predict trends likely would have overwhelming predominance of AChR-positive patients.

What Were the Safety Findings?
When it comes to safety, adverse events were common in both arms but slightly higher with satralizumab (90 percent versus 73 percent). Most were mild to moderate.

Serious events occurred in three percent of satralizumab patients versus seven percent of placebo patients.

Injection-related reactions were more frequent with satralizumab but remained non-serious and did not lead to discontinuation.

Importantly, there were no deaths or concerning laboratory trends, and infection rates were similar across groups.

How Does LUMINESCE Impact gMG Care?

The LUMINESCE trial demonstrated that AChR-IgG–positive patients experienced modest but statistically significant benefits from satralizumab.

Although satralizumab was well tolerated and biologically active, the magnitude of improvement fell short of meaningful changes in daily function or quality-of-life, raising questions about whether upstream IL-6 inhibition offers sufficient clinical value compared with newer, more targeted approaches.

Still, as the first phase 3 trial to explore IL-6 receptor inhibition in gMG, LUMINESCE highlights the cytokine’s relevance in autoantibody-mediated disease and opens the door to future research.

Reference:
Habib AA, Zhao C, Aban I, et al. Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial. Lancet Neurol. 2025;24(2):117-127. doi:10.1016/S1474-4422(24)00514-3