Enspryng eases gMG symptoms in Phase 3 trial, but falls short of hopes

While details await AAN meeting, Chugai says benefits not to 'degree' expected

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Enspryng (satralizumab), which Chugai Pharmaceutical is testing for generalized myasthenia gravis (gMG), showed a significant benefit in easing disease symptoms and their impact on daily life when used along with standard of care.

Positive results from the placebo-controlled Phase 3 LUMINESCE trial (NCT04963270), however, did not reach “the degree of clinical benefit” that the company had expected, Chugai, a member of the Roche Group, announced in a news release.

Enspryng was well tolerated, displaying a safety profile consistent with that in neuromyelitis optica spectrum disorder (NMOSD), the autoimmune disease for which the medication is approved in the U.S. and more than 80 other countries.

Detailed results will be shared in an oral presentation at the 2024 American Academy of Neurology (AAN) annual meeting, taking place on April 13–18 in Denver and online.

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Enspryng works to block a signaling protein linked to antibody production

Myasthenia gravis (MG) is an autoimmune disease that leads to muscle weakness and fatigue. MG occurs when the immune system produces self-reactive antibodies that interfere with nerve-cell communication. In gMG, disease symptoms are widespread and not confined to any specific muscle group in the body, unlike other MG types.

Enspryng contains satralizumab, which blocks the action of interleukin-6 (IL-6), a signaling protein that primes the production of antibodies and is believed to play a key role in the development of an autoimmune response. Blocking the action of IL-6 is expected to ease symptoms of autoimmune diseases.

The LUMINESCE trial, sponsored by Roche, was designed to evaluate how safe and effective Enspryng is at easing symptoms in gMG patients ages 12 and older. It may still be recruiting participants at sites in the U.S., Europe, and elsewhere.

As of September 2023, the trial had enrolled 186 patients, ages 15 to 76, who were randomly divided into two groups to be given Enspryng or a placebo through an under-the-skin injection every four weeks for about six months (24 weeks), plus an extra dose in the second week, on top of standard of care.

The majority (89.7%) tested positive for antibodies against the acetylcholine receptor (AChR), the most common type of MG-causing antibodies. Fifteen (8.2%) had antibodies targeting muscle-specific tyrosine kinase (MuSK), and four (2.2%) tested positive for antibodies against low-density lipoprotein receptor-related protein 4 (LRP4).

Patients were diagnosed at a mean age of 37.7, and the mean time since disease diagnosis was 9.2 years, according to an abstract for a poster that will also be presented at the AAN meeting by Ali Habib, MD, a neurology professor at the University of California, Irvine.

More than half (58.2%) of the patients were in MG Foundation of America (MGFA) class II, which includes those with mild weakness affecting muscles other than eye muscles, and who may also have eye muscle weakness of any severity.

A third (33.9%) of the patients had undergone a thymectomy, a surgical procedure used to remove the thymus, an immune system gland located in the upper chest under the breastbone. Thymus abnormalities are thought to play a role in the production of the self-reactive antibodies that drive MG.

LUMINESCE trial evaluating changes in patients’ daily life with treatment

The trial’s main goal is to watch for changes in the extent to which symptoms impact a patient’s daily life after 24 weeks of treatment. This will be evaluated specifically in the patient group with anti-AChR antibodies. To that end, investigators will be using an MG-specific tool called the MG Activities of Daily Living (MG‑ADL) scale; its scores range from zero to 24, with higher scores indicating more severe symptoms.

Secondary goals include assessing changes in MG‑ADL scores in all patients, as well as changes in other measures of muscle weakness, fatigue, and quality of life. Researchers also will look at the proportion of patients experiencing clinically meaningful improvements in each of those measures or who achieve minimal disease manifestation, defined an MG-ADL score of zero or one.

Data from a preclinical study in a mouse model of experimental autoimmune MG, which also will be presented in a poster at the AAN annual meeting, provided some grounds to support clinical testing of Enspryng for the treatment of gMG.

Compared with healthy mice, those with MG had weaker grip strength. They also had high levels of anti-AChR antibodies in the blood and a buildup of immunoglobulin G antibodies overlapping with AChR in muscles of the hind limbs.

MG mice treated with an antibody that blocks the IL-6 receptor didn’t develop muscle weakness. That antibody, which works like Enspryng, also decreased the production of anti-AChR antibodies and their accumulation in muscle tissues.

Enspryng has been designated an orphan drug in the U.S. as a treatment for MG, a status given to certain medications that show a potential to prevent, diagnose, or treat rare diseases.