Satralizumab Fails to Reach Expected Clinical Benefit in LUMINESCE Study of Myasthenia Gravis

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Over the 24-week treatment period, satralizumab demonstrated a well tolerated safety profile that was consistent with its previous indication.

According to an update from Chugai Pharmaceutical, the company’s genetical recombination of satralizumab (Enspryng) demonstrated statistically significant data on the primary end point in the phase 3 LUMINESCE study (NCT04963270) of patients with myasthenia gravis (MG); however, the results did not reach the expected degree of clinical benefit. Detailed results are expected to be presented as an oral Emerging Science abstract at the upcoming American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado.1

The multicenter, global trial randomly assigned 188 adults and adolescents aged 12 years and older with MG to either satralizumab or placebo for 24 weeks. Change in total Myasthenia Gravis Activities of Daily Living (MG-ADL) score among those who were anti-acetylcholine receptor (AChR)-seropositive served as the primary end point. While the therapy did not meet the investigators anticipated benefit, it did show a safety profile that was consistent with its previous indication, neuromyelitis optica spectrum disorder (NMOSD).

Satralizumab, a pH-dependent binding humanized anti-interleukin-6 monoclonal receptor antibody, was first approved for patients with aquaporin-4-positive NMOSD in 2020 following the phase 3 SAkuraStar (NCT02073279) and SAkuraSky (NCT02028884) clinical trials. At the time, it joined Alexion’s eculizumab (Soliris) and Horizon’s inebilizumab (Uplizna) as the only approved therapies for the autoimmune condition.2

In addition to change in MG-ADL, LUMINESCE also assesses other outcomes of Qualitative Myasthenia Gravis (QMG) score, Myasthenia Gravis Quality of Life 15 Scale (MG-QOL-15) score, Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Subscale score, and total Myasthenia Gravis Composite (MGC) Score. The trial also evaluates the proportion of patients who experienced clinically meaningful improvement of MG-ADL, QMG, or MGC scores or who achieved minimal disease manifestation. Several different types of MG, including AChR+, muscle-specific tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 MG, also were assessed on the primary end point.

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Satralizumab is also being assessed in the METEOROID study (NCT05271409), which is the first of its kind in patients with myelin oligodendrocyte glycoprotein antibody disease (MOGAD). MOGAD, an autoimmune disorder, is characterized by changes in vision and symptoms caused by spinal cord inflammation that present similarly to other demyelinating disorders, such as NMOSD and multiple sclerosis (MS). METEOROID, a phase 3 study, will recruit patients from approximately 80 sites across 9 countries globally, with 7 sites each in Germany and Italy, and 3 sites in France.

Previous research has suggested that IL-6 has a role in the pathogenesis of MOGAD, and that IL-6-directed therapy has shown to provide clinical benefit for relapse protection in this patient population.3 In METEOROID, 152 individuals with MOGAD will undergo a 28-day screening period, followed by a 44-month treatment period and concluding with a 24-month open-label extension, with all patients switching or staying on satralizumab. The study’s primary end point is time from randomization of a MOGAD relapse in the double-blind period, as determined by an adjudication committee.

REFERENCES
1. Results of phase 3 study of Enspryng in patients with generalized myasthenia gravis. Chugai Pharmaceutical. March 21, 2024. Accessed March 26, 2024. https://www.chugai-pharm.co.jp/english/news/detail/20240321150000_1059.html
2. FDA approves Genentech’s Enspryng for neuromyelitis optica spectrum disorder. News release. Genentech. August 14, 2020. Accessed March 26, 2024. https://www.businesswire.com/news/home/20200814005501/en/ADDING-MULTIMEDIA%C2%A0FDA-Approves-Genentech%E2%80%99s-Enspryng-Neuromyelitis-Optica
3. Ringelstein M, Ayzenberg I, Lindenblatt G, et al. Interleukin-6 receptor blockade in treatment-refractory MOG-IgG-associated disease and neuromyelitis optica spectrum disorders. Neurol Neuroimmunol Neuroinflamm. 2021;9(1):e1100. doi:10.1212/NXI.0000000000001100
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