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Amgen announced the European Commission (EC) has approved Uplizna (inebilizumab) as an add-on treatment to standard therapy for adults living with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) or anti-muscle specific tyrosine kinase (MuSK) antibody positive. The approval offers patients a new, targeted treatment option with the potential for long-term disease control through twice-yearly maintenance dosing, following two initial loading doses.
Generalized myasthenia gravis is a rare, unpredictable, chronic, B-cell-mediated autoimmune disease that causes fluctuating muscle weakness and can impact quality of life. It is a subtype of myasthenia gravis (MG), which affects an estimated 56,000-123,000 people in Europe.
"This approval represents an important advancement for adults with gMG in Europe, helping address debilitating symptoms and potentially reduce the long-term use of steroids where clinically appropriate," said Cesar Sanz Rodriguez, vice president of medical affairs at Amgen. "With convenient twice-yearly dosing and durable efficacy in people with anti-AChR and anti-MuSK antibody positive gMG, Uplizna brings a new first-in-class approach to managing this complex disease."
The EC approval is supported by data from the Myasthenia Gravis Inebilizumab Trial (MINT), the largest phase 3 biologic study to include both AChR+ and MuSK+ patients, and the first to successfully incorporate a structured steroid-tapering protocol. Patients receiving steroids at baseline began tapering at Week 4 with a goal of reaching prednisone 5 mg per day by Week 24. By Week 26, 87.4% of patients taking Uplizna and 84.6% of those taking placebo had reduced their steroid dose to 5 mg or less per day.
"Uplizna offers a new approach to treating gMG by selectively targeting CD19-positive B cells, which play a key role in disease pathology," said John Vissing, MD, DMSci, professor of neurology and director of the Copenhagen Neuromuscular Center, Rigshospitalet, at the University of Copenhagen. "The approval provides both clinicians and patients a valuable new treatment option with the potential for long-term efficacy while addressing the challenges of long-term steroid exposure."
The approval in gMG builds on Uplizna's established efficacy in rare autoimmune conditions, including its November 2025 EC approval as the first and only treatment for adults living with active immunoglobulin G4-related disease (IgG4-RD), a chronic and debilitating immune-mediated inflammatory condition that can affect multiple organs. Uplizna was also previously approved as a monotherapy for adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive.
Uplizna has received regulatory approvals across multiple indications from the US Food and Drug Administration, Health Canada, and the Brazilian Health Regulatory Agency (ANVISA), among others.
MINT is a randomized, double-blind, placebo-controlled, parallel-group trial (NCT04524273) designed to evaluate the efficacy and safety of Uplizna in adults with gMG. The trial enrolled 238 adults with gMG, including 190 patients who are AChR+ and 48 patients who are MuSK+.
Eligibility criteria at screening and randomization included a Myasthenia Gravis Foundation of America (MGFA) classification of II, III or IV disease, MG-ADL score between 6 and 10 with greater than 50% of this score attributed to non-ocular items, or an MG-ADL score of at least 11, and a Quantitative Myasthenia Gravis (QMG) score of at least 11. Participants had to have been receiving a stable dose of steroids and/or nonsteroidal immunosuppressive therapy (or both) at the time of randomization.
The primary endpoint was change from baseline in MG-ADL score at Week 26 in the combined study population. Key secondary endpoints included change from baseline in QMG scores in the combined study population; change from baseline in MG-ADL score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort; and change from baseline in QMG score at Week 26 for the AChR+ cohort and separately the MuSK+ cohort. MINT also includes an optional three-year open-label treatment period.
Key findings from MINT include:
Primary endpoint:
• A 1.9-point difference in the MG-ADL score for Uplizna (-4.2) compared to placebo (-2.2) (p<0.0001) at Week 26 for the combined study population.
Key secondary endpoints:
• A 2.5-point difference in the QMG score for Uplizna (-4.8) compared to placebo (-2.3) (p=0.0002) at Week 26 for the combined treated population.
• A 1.8-point difference in the MG-ADL score for Uplizna (-4.2) compared to placebo (-2.4) (p=0.0015) at Week 26 for the AChR+ population.
• A 2.5-point difference in the QMG score for Uplizna (-4.4) compared to placebo (-2.0) (p=0.0011) at Week 26 for the AChR+ population.
• A 2.2-point difference in the MG-ADL score for Uplizna (-3.9) compared to placebo (-1.7) (p=0.0297) at Week 26 for the MuSK+ population.
• A 2.3-point difference in the QMG score for Uplizna (-5.2) compared to placebo (-3.0) (p=0.1326) at Week 26 for the MuSK+ population; this difference was not statistically significant.
Additional exploratory endpoints:
• A 2.8-point difference (95% CI: -3.9 to -1.7) in the MG-ADL score for Uplizna (-4.7) compared with placebo (-1.9) at Week 52 for the AChR+ population.
• A 4.3-point difference (95% CI: -5.9 to -2.8) in the QMG score for Uplizna (-5.8) compared with placebo (-1.4) at Week 52 for the AChR+ population.
• 87.4% of Uplizna patients and 84.6% of those taking placebo reduced their steroid dose to 5 mg or less per day by Week 26.
MG-ADL scale, which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG. Each item is assessed on a 4-point scale, where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. The total MG-ADL score ranges from 0 to 24, with higher scores indicating more impairment.
The QMG score is a 13-item categorical grading system that quantitively measures disease impairment by mainly assessing muscle weakness. Each item is assessed on a 4-point scale where a score of 0 represents no impairment weakness and a score of 3 represents severe impairment weakness. A total possible score ranges from 0 to 39, where higher scores indicate more severe impairment.
Generalized myasthenia gravis (gMG) is a rare, chronic, B-cell-mediated autoimmune disorder that impairs neuromuscular communication and can cause muscle weakness, trouble breathing, difficulty swallowing and impaired speech and vision.
Approximately 85% of patients with myasthenia gravis have the generalized form, or gMG. The prevalence and incidence of gMG are increasing worldwide. There are an estimated 56,000 to 123,000 people with myasthenia gravis in Europe, with prevalence rates in different countries varying significantly. Approximately 85% of patients with myasthenia gravis have detectable antibodies against AChR, and approximately 7% have detectable antibodies against MuSK. Global prevalence is estimated at 2-36 cases per 100,000. The disease is more frequently seen in young women (age 20-30) and men aged 50 years and older.
B cells are central to the pathogenesis of gMG. The disease is thought to be primarily driven by pathogenic CD19+ plasmablasts and plasma cells that target critical proteins in the neuromuscular junction.
Uplizna is a humanized monoclonal antibody (mAb) that causes targeted and sustained depletion of key cells that contribute to the underlying disease process (autoantibody-producing CD19+ B cells, including plasmablasts and some plasma cells). The precise mechanism by which Uplizna exerts its therapeutic effects is unknown. After two initial infusions, patients need one maintenance dose of Uplizna every six months.
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