SAN DIEGO — Inebilizumab (Uplizna, Amgen) is safe and effective up to 52 weeks in patients with generalized myasthenia gravis (MG), new research suggested.
If approved, the drug would potentially be a first-in-class humanized monoclonal agent that targets CD19+ B cells.
The phase 3 MINT trial included more than 200 adults with anti–acetylcholine receptor antibody–positive (AChR+) or muscle-specific kinase antibody–positive (MuSK+) generalized MG.
In the full patient population, those who received inebilizumab had greater score improvement on the Myasthenia Gravis Activities of Daily Living scale (MG-ADL) at 26 weeks than those who received placebo, meeting its primary endpoint.
The active treatment also met key secondary outcomes at 26 weeks, including change in Quantitative Myasthenia Gravis (QMG) scores.
These findings were presented on April 8 at the American Academy of Neurology (AAN) 2025 annual meeting and were published simultaneously in The New England Journal of Medicine.
In addition, 52-week results in just the AChR+ subgroup were presented later in the day at a late-breaking scientific session. This presentation also showed significant improvement in the same primary and secondary outcomes.
Taken together, the MINT trial “establishes definitively” the role of CD19+ B-cell–targeted therapy for MG, said global principal study investigator Richard J. Nowak, MD, director of the Myasthenia Gravis Clinic at Yale University, New Haven, Connecticut.
“We’ll need to delve deeper into the data, but it most certainly establishes the efficacy of a new class of medication,” Nowak told Medscape Medical News.
‘Moves the Needle Forward’
Inebilizumab is already approved for neuromyelitis optica spectrum disorder (NMOSD) and, as of last week, for immunoglobulin G4-related disease. Regulatory filing activities are also currently underway as treatment for generalized MG, a company representative told Medscape Medical News.
Nowak, who is also an associate professor of neurology at Yale School of Medicine, New Haven, Connecticut, noted that there continues to be an unmet need for patients with MG.
“About 15% and maybe up to 20% have medically refractory or inadequately controlled disease,” he said. “I think having additional therapies, particularly in another class, really does move the needle forward.”
The MINT study included 238 total patients enrolled at 81 sites across 18 countries. Of these participants, 190 were AChR+ and 48 were MuSK+.
Nowak noted that this was the largest group of patients with MuSK+ ever included in a randomized MG trial. He added that MuSK+ accounts for about 5%-10% of patients with generalized MG.
In the combined population, 119 patients received 300 mg of intravenous inebilizumab (mean age, 47.1 years; 66.4% women) and the other 119 received matching placebo (mean age, 47.9 years; 55.6% women). Each treatment group had 95 AChR+ and 24 MuSK+ participants.
The protocol consisted of administration on Day 1 of randomization and on Day 15 for all participants. The AChR+ subgroup also received administration at week 26.
Additionally, prednisone use in participants who were taking corticosteroids was tapered starting at week 4. It was reduced to 5 mg/d by week 24.
Nowak noted that chronic use of corticosteroids have several known adverse events (AEs), including weight gain and risk for osteoporosis, especially at moderate to high doses. Because of the lengthy endpoints in the study, “we wanted to try to reduce the burden of steroids and not subject patients to unwanted or unnecessary side effects during the trial period,” he said.
The primary endpoint for this primary analysis was change from baseline to week 26 on the MG-ADL in the entire group. Secondary measures included change from baseline to week 26 on the QMG for entire group, and on the MG-ADL and QMG in the two antibody subgroups separately.
Clinically Meaningful
Results showed a “clinically meaningful improvement” in MG-ADL score change in the full inebilizumab (−4.2) vs full placebo (−2.2) groups at week 26 (adjusted group difference, −1.9; 95% CI, −2.9 to −1.0; P < .001), Nowak reported.
The active treatment group also had greater QMG score improvement (−4.8 vs −2.3; adjusted difference, −2.5; P < .001).
Separately, each of the AChR+ and MuSK+ subgroups taking inebilizumab had significant change in MG-ADL scores vs placebo (adjusted differences, −1.8 and −2.2, respectively; P < .05 for both). However, only the AChR+ subgroup taking inebilizumab showed significant change in QMG score vs placebo (adjusted difference, −2.5; P < .05).
In the full active treatment group, 80.7% reported AEs compared with 73.1% in the full placebo group. Serious AEs occurred in 8.4% and 13.4%, respectively. The percentage of study participants with AEs were similar in the AChR+ and MuSK+ subgroups.
Headache, cough, nasopharyngitis, and infusion-related reactions were the most common AEs reported by the inebilizumab group. The treatment-emergent AE profile during the trial was “consistent with the known safety profile” for the treatment of NMOSD, Nowak noted.
Overall, the findings “support the role of anti-CD19 B-cell depletion therapy” for MG, he told meeting attendees.
“Targeting an upstream immunopathogenic mechanism may be an effective tool in reducing disease severity and steroid burden,” the investigators added in the journal article.
One-Year Safety, Efficacy
Patients with AChR+ were also assessed up to 52 weeks “to better understand the durability and magnitude of response over time,” Nowak said.
Asked why patients with MuSK+ weren’t included in the longer-term evaluations, he said that prior work had suggested that this population might have a quicker time to treatment response. So 26 weeks seemed like a reasonable endpoint for them — although they were also allowed to enroll in a 3-year open-label extension, he added.
Results for the analysis in patients with AChR+ showed that 72.3% of those in the active treatment group had at least a three-point improvement on the MG-ADL at 52 weeks compared with 45.2% of those in the placebo group (P < .001); and 69.2% vs 41.8%, respectively, had at least a three-point improvement on the QMG (P < .001).
The adjusted difference in improvement in MG-ADL score for the active treatment vs placebo groups was significant starting at 26 weeks and increased at 32, 38, 44, and 52 weeks. The adjusted difference in change from baseline to the last timepoint for inebilizumab vs placebo was −2.8 (95% CI, −3.9 to −1.7; P < .001).
The same pattern of continued improvement was found on QMG scores, with a significant between-group difference starting at 18 weeks and increasing to study’s end. The adjusted difference in change from baseline to 52 weeks was −4.3 for inebilizumab vs placebo (95% CI, −5.9 to −2.8; P < .001).
In addition to the optional open-label period, with inebilizumab administered every 6 months for 3 years, ongoing plans for the MINT study include a safety follow-up; and further endpoints will include steroid tapering and quality of life issues.
Excited, but Frustrated
Commenting for Medscape Medical News, Henry J Kaminski, MD, professor of neurosciences at George Washington University, Washington DC, noted that the trial demonstrated efficacy for inebilizumab with improved MG-ADL score, the standard primary outcome measure for MG clinical trials.
However, he was concerned about the low response in the primary/26-week results, even though a two-point difference on the MG-ADL is considered clinically meaningful.
“I am excited to see another positive trial in MG but again am frustrated by the lack of a better response,” he said. Kaminski, who is also principal investigator for the MGNet Rare Disease Clinical Research Network, was not involved with the MINT study.
He also called out the mean QMG score. It went down from 16.7 at baseline to 12.2 at 26 weeks in the inebilizumab group vs a decrease from 17.3 to 14.8 in the placebo group. However, Kaminski said that the 26-week score of 12 for the active treatment still “indicates a significant weakness.”
“Given the drug is targeting the pathogenic antibody producing cells, there would be the expectation of much better disease control,” he said. “A goal now should be a deep dive into characterizing the underlying immunological phenotype of subjects over the course of the trial in both arms of the study.”
Questions he’d like to see answered include: Whether CD19 cells effectively eliminated? What about changes in specific B-cell subsets? Were there greater reductions in high responders? Also, how did autoantibody levels change?
“As clinicians and scientists studying MG, we should reach for outcomes for trials that are better than ADL improvement of only two points. This is particularly important for treatments that run into hundreds of thousands of dollars per year,” Kaminski concluded.
As reported at the time by Medscape Medical News, topline 26-week results were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine meeting in October.
This study was funded by Amgen. Nowak reported having numerous disclosures, including receiving research support from and serving as a consultant and advisor for Viela Bio, Inc. (Horizon Therapeutics, now Amgen). Kaminski also reported numerous relationships but noted that there were no conflicts with this study.
