Enspryng is safe, but clinical benefit ‘small’ in gMG, trial data show
Also, no added improvements seen in assessments after initial study period
Enspryng (satralizumab), tested by Chugai Pharmaceutical as a treatment for generalized myasthenia gravis (gMG), eased disease symptoms and made daily life easier when used in addition to standard of care therapy over six months, but its clinical benefit was somewhat limited.
These data from LUMINESCE (NCT04963270), a Phase 3 clinical trial that tested how safe Enspryng is compared with a placebo and how well it works in adults and adolescents with gMG, fell short of what Chugai, a member of the Roche Group, had initially expected.
Despite the “small improvements” seen in the trial, Enspryng was safe and well tolerated, with side effects similar to those seen with its use in neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease for which the therapy is already approved in the U.S. and more than 80 other countries.
However, the researchers noted that, in an open-label extension following the initial study period, no additional improvements of note were seen in patients given Enspryng versus the placebo. Substantial gains were not seen in assessment scores for the treated participants, per the study.
The study, “Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial,” was published in the journal The Lancet Neurology. The work was funded by Roche; Genetech, also part of the Roche Group, markets Enspryng for NMOSD. About a third of the study’s researchers work for a Roche company.
LUMINESCE tested Enspryng in over 150 gMG patients
Myasthenia gravis, or MG, is an autoimmune disease that leads to muscle weakness. It occurs when the immune system produces self-reactive antibodies that disrupt the communication between nerve and muscle cells. In generalized MG, called gMG, symptoms affect different muscle groups, including those responsible for controlling eye movements, speech, swallowing, and limb movements.
Enspryng is an antibody-based therapy that’s designed to block the action of interleukin-6, known as IL-6, which is a signaling protein that stimulates immune cells to produce antibodies — including the autoantibodies that play a role in the development of an autoimmune response. Blocking the action of IL-6 is expected to ease the symptoms of gMG.
The LUMINESCE study, completed last year, enrolled 188 adults and adolescents, ages 12 and older, with gMG. All were randomly assigned to receive either Enspryng or a placebo as a subcutaneous, or under-the-skin, injection at weeks 0, 2, and 4, and every four weeks thereafter. Treatment was administered in addition to standard of care. The study period spanned 24 weeks, or about six months.
Participants who completed that randomized, double-blinded period of LUMINESCE could enter an open-label extension to continue treatment with Enspryng for up to two years. This extension period ended early due to the company’s decision to stop developing Enspryng for gMG, according to the researchers.
Slightly more than half of the participants (57.4%) were classified into the MG Foundation of America class II. Individuals in that class have mild weakness in muscles other than those controlling eye movements — typically first affected in MG — though eye muscles may also be affected to some extent.
About one-third (33.5%) had a history of thymectomy, a surgical procedure to remove the thymus, an immune organ located in the chest. Abnormalities in the thymus are believed to contribute to the production of self-reactive antibodies that drive MG.
The intention-to-treat population included 166 patients who tested positive for antibodies against the acetylcholine receptor, or AChR, the most common type of MG-causing antibodies, with at least one MG Activities of Daily Living (MG-ADL) score assessment after the study started. The MG-ADL scale reflects how the disease affects daily life, with higher scores indicating more severe symptoms.
No substantial score gains seen in open-label extension portion
The study’s main goal was to watch for changes in MG‑ADL scores in the intention-to-treat population. After 24 weeks, MG-ADL scores dropped by a mean of 3.59 points in Enspryng-treated patients and by 2.57 points in those on the placebo. The difference of 1.02 points was “statistically significant yet small,” according to the researchers.
Secondary goals included assessing changes in Quantitative MG (QMG) scores, where higher scores again indicate more severe symptoms. QMG scores dropped by a mean of 3.41 points in the Enspryng group, 1.63 points more than in the placebo group. These “small improvements” were also significant.
While a response was seen as early as after four weeks of treatment, “no further substantial improvement in MG-ADL and QMG scores was observed in the [Enspryng] group during the open-label extension period beyond the effect achieved by week 24 of the double-blind period,” the researchers wrote.
No further substantial improvement in [assessment scores] was observed in the [Enspryng] group during the open-label extension period beyond the effect achieved by week 24 of the double-blind period.
More patients reported at least one side effect with Enspryng compared with the placebo (90% vs. 73%). In nearly half (47%), side effects were considered to be related to treatment; in the placebo group, this percentage was smaller (22%). Most side effects were mild or moderate in severity.
Noting that “in the LUMINESCE study, [Enspryng] resulted in small improvements in measures of disease severity and daily living in patients … relative to [the] placebo,” the team concluded that the findings overall support further research into the therapy’s effects in gMG and other conditions.
“Further research [analyzing] the immunological underpinnings of the observed clinical response … in patients with [generalized] myasthenia gravis … is warranted,” the researchers wrote. “Future research should continue to elucidate the role of IL-6 in autoantibody-driven diseases.”
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