Inebilizumab for myasthenia gravis

Last updated Oct. 11, 2024, by Joana Carvalho, PhD
Fact-checked by Inês Martins, PhD

What is inebilizumab for myasthenia gravis?

Inebilizumab is an antibody-based therapy, designed to reduce the levels of certain immune cells in the body, that developer Amgen is now advancing for myasthenia gravis (MG). The therapy aims to ease disease symptoms in people with MG. It would be administered via intravenous, or into-the-vein, infusions, every six months.

While still in Phase 3 testing for MG, inebilizumab is already approved under the brand name Uplizna for neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that affects the nervous system. It also is being investigated as a potential treatment for a chronic inflammatory condition called immunoglobulin G4-related disease.

Therapy snapshot

How does inebilizumab work in myasthenia gravis?

MG is an autoimmune condition in which self-reactive antibodies mistakenly attack proteins involved in nerve-muscle communication, resulting in the disease’s hallmark symptoms of muscle weakness and fatigue. These autoantibodies are produced by a type of immune cells called B-cells.

Inebilizumab is an antibody-based therapy that’s designed to bind to CD19, a protein found on the surface of B-cells. Once bound to CD19, it triggers a process called antibody-dependent cell-mediated cytotoxicity, where certain immune cells recognize and kill cells that are bound to an antibody.

Through this mechanism, inebilizumab can deplete or lower the number of B-cells, and consequently reduce the levels of MG-causing antibodies, which is expected to help ease disease activity and symptoms.

How will inebilizumab be administered in myasthenia gravis?

In a Phase 3 clinical trial involving people with generalized MG (gMG), inebilizumab is being administered in the form of intravenous infusions containing 300 mg of the therapy’s active ingredient. The first two are given two weeks apart, and subsequent ones are then given every six months.

However, because inebilizumab is still in the early stages of development for gMG, it’s too soon to know if this will be the therapy’s dosing regimen once, and if, it’s ultimately approved for this indication.

Inebilizumab in myasthenia gravis clinical trials

An ongoing Phase 3 clinical trial called MINT (NCT04524273) is evaluating the safety and efficacy of inebilizumab in adults with gMG who are positive for self-reactive antibodies targeting the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). These are the two most common types of MG-causing antibodies.

The trial enrolled 238 patients, who were randomly assigned to receive intravenous infusions of 300 mg of inebilizumab or a placebo, both given in addition to standard-of-care treatment. Patients who were positive for anti-AChR antibodies received three doses of inebilizumab (the first two are given two weeks apart, and the third six months later), while those positive for anti-MuSK antibodies received two doses separated by two weeks.

After completing the randomized treatment period, which will last six months for patients with anti-MuSK antibodies and one year for those with anti-AChR antibodies, all will have the option to enroll in an open-label extension to continue receiving inebilizumab. In this part, those who were initially on the placebo will also start treatment with two doses given two weeks apart, after which all will receive the therapy every six months for up to three years.

The trial’s main goal is to assess changes in the MG Activities of Daily Living (MG-ADL), a patient-reported measure of MG severity and impact on daily life activities, over the course of 26 weeks, or about six months. For secondary goals, researchers will also measure changes in other assessments of disease severity, including the Quantitative MG (QMG) and the MG Composite scales, as well as quality-of-life and patient-reported outcomes.

Top-line data from the study, gathered when all patients had completed 26 weeks of follow-up, showed there was a clinically meaningful and statistically significant reduction in MG-ADL scores after two doses of inebilizumab compared with the placebo, indicating less severe disease.

Specifically, data showed that in patients treated with inebilizumab, MG-ADL scores dropped by 4.2 points, a significant difference from the 2.3-point reduction in the placebo group. Clinically meaningful and statistically significant benefits in these scores were also seen among the subgroups of patients who were positive for anti-AChR and anti-MuSK antibodies.

Statistically significant improvements were also seen in key secondary measures, particularly in the QMG scores, which dropped by 4.8 points with inebilizumab and by 2.3 points with the placebo. No new safety issues were reported.

The trial is expected to conclude in 2027.

Common side effects of inebilizumab

Clinical trials of inebilizumab in people with gMG are ongoing, with no new safety issues reported to date. However, the therapy’s specific safety profile in this patient population is still unknown.

In people with NMOSD, an indication for which inebilizumab is already approved, common side effects include urinary tract infections and joint pain. However, more data will be needed to know if these side effects are also common in gMG patients who receive the medication.

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