Inebilizumab reduces gMG severity in Phase 3 trial: Top-line data
Therapy effective against both AChR, MuSK antibody-positive patients
Amgen’s antibody-based therapy inebilizumab reduces the severity of generalized myasthenia gravis (MG), according to top-line data from a Phase 3 clinical trial.
Dubbed MINT (NCT04524273), the study showed inebilizumab’s therapeutic efficacy in gMG patients who test positive for self-reactive antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK), the two most common types of MG-causing antibodies.
“We’re excited about these data, with the potential to address the continued unmet need in generalized myasthenia gravis,” Jay Bradner, MD, executive vice president of research and development at Amgen, said in a company webcast.
Inebilizumab is approved as Uplizna for neuromyelitis optica spectrum disorder (NMOSD), an autoimmune disease that affects the spinal cord and the optic nerve, which sends and receives signals from the eye.
An autoimmune disorder, gMG is caused by the abnormal production of self-reactive antibodies that damage the neuromuscular junction, where nerves connect to the muscles they control. These antibodies primarily target AChR or MuSK proteins within the neuromuscular junction.
Common symptoms include muscle weakness, fatigue, drooping eyelids, difficulty breathing, trouble swallowing, impaired speech, or disability. While there’s no cure for gMG, treatments, such as medications, surgery, or other procedures, are intended to suppress the immune system’s harmful effects or restore nerve-muscle communication.
“There are treatments available, but there’s significant unmet need, and importantly, patients could stand to benefit from more durable response, less frequent dosing, and new medicines that would allow the tapering of steroids,” Bradner said.
What is inebilizumab, how does it work on gMG?
Inebilizumab, given by infusions into the vein, or intravenously, is an antibody-based therapy that’s made to bind to CD19, a protein on the surface of immune B-cells, where triggers the death of these cells, which drive autoimmune diseases like gMG. By depleting or reducing the number of B-cells harboring CD19, inebilizumab may lower the production of self-reactive antibodies, decrease disease activity, and ease gMG symptoms.
MINT is an ongoing Phase 3, placebo-controlled study that enrolled 238 patients with gMG — 190 who tested positive for anti-AChR antibodies and 48 who were positive for anti-MuSK antibodies. Its participants were randomly assigned to either 300 mg of inebilizumab or placebo, given 15 days apart at the start of the study, with an additional dose after six months and follow-up at one year (in the case of those positive for anti-AChR antibodies). All patients may enroll in an open-label extension thereafter to continue receiving inebilizumab.
Starting at week 4, all patients on corticosteroids will undergo tapering to 5 mg or less per day by week 24.
“Steroids are often used to treat myasthenia gravis patients, but prolonged high-dose steroid use can have pretty harmful effects,” said Vikram Karnani, Amgen’s rare disease chief. “All of our competitor trials allowed patients to remain on background therapy, including steroids.”
The study’s main goal is to assess inebilizumab’s ability to improve the scores of the MG Activities of Daily Living (MG-ADL) , a patient-reported scale that assesses MG symptoms and their impact on daily activities, at week 26, after about six months of treatment.
Across all the participants, top-line data at six months showed a clinically meaningful and statistically significant MG-ADL score improvement after two doses of inebilizumab compared with the placebo. Specifically, inebilizumab-treated patients saw their MG-ADL scores drop by 4.2 points, while those on a placebo saw a drop of 2.3 points.
In a key secondary measure, inebilizumab also significantly outperformed the placebo in lowering the score of the Quantitative MG (QMG), a physician-guided measure of disease severity. In this measure, inebilizumab-treated patients had an overall 4.8-point reduction, whereas those on placebo had a 2.3-point reduction.
No new safety signals were identified.
More data from MINT will be presented at the annual meeting of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) in October in Georgia, according to Bradner.
“[Inebilizumab] has a pretty unique and differentiated product profile, which makes it a very meaningful treatment option for MG patients,” Karnani said.
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