Amgen Reveals Positive Phase 3 Data for Uplizna in Generalized Myasthenia Gravis at AANEM 2024

Amgen has announced promising results from the Phase 3 MINT trial, which evaluated the efficacy and safety of UPLIZNA® (inebilizumab-cdon) for treating adults with generalized myasthenia gravis (gMG). This condition is a rare autoimmune disorder that affects neuromuscular communication. The trial results will be presented at the Myasthenia Gravis Foundation of America (MGFA) Scientific Session during the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Annual Meeting in Savannah, Georgia.

The Phase 3 MINT trial, a randomized, double-blind, placebo-controlled, parallel-group study, met its primary endpoint by showing a statistically significant improvement in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score for UPLIZNA compared to placebo at Week 26. Participants receiving UPLIZNA showed a -4.2 change from baseline in their MG-ADL score versus a -2.2 change in those receiving placebo, with a difference of -1.9, p<0.0001. The study included patients with acetylcholine receptor autoantibody-positive (AChR+) and muscle-specific kinase autoantibody-positive (MuSK+) conditions. UPLIZNA was administered on Day 1 and Day 15 of the trial, and continued to show improvement through Week 26. Furthermore, patients on corticosteroids at the study's start were tapered to a prednisone dose of 5 mg per day by Week 24. No new safety concerns emerged during the trial.

Dr. Jay Bradner, Amgen's executive vice president of Research and Development and chief scientific officer, highlighted the importance of UPLIZNA as a new treatment option for patients suffering from gMG, offering long-term symptom relief. UPLIZNA targets CD19+ pre-B cells, mature B-cells, and some plasmablasts, which are key drivers of the disease. The results from the MINT trial bolster evidence for UPLIZNA's efficacy in severe autoimmune diseases and emphasize Amgen's leadership in B-cell targeting therapies.

Secondary endpoints in the trial were also achieved in a predefined sequential order, with significant and meaningful improvements from baseline compared to placebo for the initial four key secondary endpoints. UPLIZNA showed a -4.8 change in Quantitative Myasthenia Gravis (QMG) score compared to placebo's -2.3 at Week 26, with a difference of -2.5, p=0.0002. For the AChR+ population, UPLIZNA showed a -4.2 change in MG-ADL score compared to -2.4 for placebo (difference: -1.8, p=0.0015) and a -4.4 change in QMG score compared to -2.0 for placebo (difference: -2.5, p=0.0011). In the MuSK+ population, UPLIZNA showed a -3.9 change in MG-ADL score compared to -1.7 for placebo (difference: -2.2, p=0.0297). As for QMG score in the MuSK+ population, UPLIZNA showed a trend towards improvement but was not statistically significant (-5.2 for UPLIZNA vs. -3.0 for placebo, difference -2.3, p=0.1326).

Dr. Richard J. Nowak, the global principal study investigator and director of the Myasthenia Gravis Clinic at Yale University, emphasized the significant impact of gMG on patients' lives, causing severe muscle weakness and impairing daily functioning. He noted that the trial results demonstrate UPLIZNA's clinically meaningful benefits, highlighting its unique mechanism of action in selectively targeting and depleting CD19+ B cells, which are crucial in the pathogenesis of gMG. The MINT trial is also noteworthy as the only Phase 3 biologic trial that included a protocol-specified steroid taper.

Safety results during the placebo-controlled period were consistent with known safety profiles of UPLIZNA. The most common adverse events were COVID-19, nasopharyngitis, urinary tract infection, infusion-related reactions, headache, and cough.

The MINT trial is the largest placebo-controlled gMG clinical trial for a biologic therapy, enrolling 238 adults, which included 190 AChR+ patients and 48 MuSK+ patients. Further data will elucidate UPLIZNA's placebo-controlled efficacy and safety over a 12-month period in AChR+ patients with gMG.

In addition to the MINT trial results, Amgen will present a poster at the 2024 AANEM Annual Meeting discussing the burden of glucocorticoid use among gMG patients in the U.S., noting the association between higher glucocorticoid use and increased toxicities and healthcare costs.

UPLIZNA is already approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with AQP4 antibody positivity in several countries, including the U.S., European Union, Brazil, and Canada. Recently, UPLIZNA also received Breakthrough Therapy Designation for IgG4-Related Diseases from the FDA. Based on the MINT trial results, Amgen plans to seek approval for UPLIZNA in the U.S. and other key markets.