Uplizna Improves Myasthenia Gravis

The results demonstrated durable and sustained efficacy of Uplizna in patients with acetylcholine receptor autoantibody-positive (AChR+) gMG with two doses a year, following an initial loading dose. Findings will be presented as a late-breaking oral presentation during the American Academy of Neurology (AAN) Annual Meeting on April 8, 2025, in San Diego.

The Phase III MINT trial, which was a randomized-control trial, evaluated Uplizna in muscle-specific kinase autoantibody-positive (MuSK+) and AChR+ gMG patients, with the MuSK+ group followed for 26 weeks and the AChR+ group followed for 52 weeks. The trial demonstrated continued improvement in efficacy of Uplizna  compared to placebo (adjusted difference, −2.8, 95% CI, −3.9 to −1.7) as measured by the change in baseline of Myasthenia Gravis Activities of Daily Living (MG-ADL) score in the AChR+ subpopulation at week 52. Among the AChR+ patients in the Uplizna  group, 72.3% had a ≥3 point improvement in the MG-ADL score, compared to 45.2% in placebo.

As previously disclosed at the 2024 American Association of Neuromuscular & Electrodiagnostic Medicine Annual Meeting, the trial met its primary endpoint, with a statistically significant change from baseline in MG-ADL score for UPLIZNA (-4.2) compared with placebo (-2.2) (difference: –1.9, p<0.0001) at Week 26 for the combined study population.

Change from baseline in the Quantitative Myasthenia Gravis (QMG) score was also greater for patients in the Uplizna group as compared to placebo at Week 52 (adjusted difference, −4.3, 95% CI, −5.9 to −2.8). Among the AChR+ patients in the UPLIZNA group, 69.2% improved by ≥3 points in the QMG score, compared to 41.8% in the placebo group.

MINT was the first and only Phase III trial for a biologic to incorporate a corticosteroid taper into its protocol. Patients who entered the study taking corticosteroids were tapered down starting at Week 4 to prednisone 5 mg per day by Week 24. No new safety signals were identified. The overall TEAE profile during the study period is consistent with the known safety profile for the approved indication (NMOSD). The most common adverse events included infusion-related reactions, nasopharyngitis and urinary tract infections.

The MINT trial is a randomized, double-blind, placebo-controlled, parallel-group trial (NCT04524273) evaluating the efficacy and safety of Uplizna in adults with gMG. The trial enrolled 238 adults with gMG, including 190 patients who are acetylcholine receptor autoantibody-positive (AChR+) and 48 patients who are muscle-specific kinase autoantibody-positive (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, QMG score of at least 11, and use of a corticosteroid and/or non-steroidal immunosuppressant.

The primary endpoint was change from baseline in MG-ADL score at Week 26 in the combined 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. Patients who entered the study taking a corticosteroid were tapered down to prednisone 5 mg a day, starting at Week 4 to Week 24. The MINT trial also includes an optional three-year open-label treatment period.

 "I'm looking forward to further examining the 52-week MINT data with my colleagues in the neurology community at AAN," said Dr. Richard J. Nowak, global principal study investigator and director of the Myasthenia Gravis Clinic at Yale University. "These results showed that UPLIZNA consistently relieved burdensome symptoms and improved activities of daily living for gMG patients."

"The 52-week MINT trial results highlight the potential for a new standard of care in gMG, offering durable symptom relief with a simplified treatment regimen," said Dr. Jay Bradner, executive VP  of Research and Development at Amgen. "These findings reinforce UPLIZNA's ability to provide sustained symptom relief with just two doses per year—an important advancement for patients living with generalized myasthenia gravis—while underscoring our commitment to developing transformative  therapies for people facing complex autoimmune diseases."