52-Week MINT Data Confirm Inebilizumab Benefit in AChR+ gMG: Richard Nowak, MD, MS

New topline data from the MINT trial (NCT04524273), which is investigating inebilizumab in patients with generalized myasthenia gravis who are acetylcholine receptor (AChR) antibody or muscle-specific kinase (MuSK) positive, have been released. These results show the intravenous monoclonal antibody producing statistically significant reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores vs placebo at 52 weeks among patients who are AChR positive. A significant number of patients were also able to achieve improvements in those scores of 3 or more points.

Topline data through week 26 were presented at the recent American Association of Neuromuscular & Electrodiagnostic Medicine meeting and the 2025 MDA Clinical & Scientific Conference.

In this first part of an interview with The American Journal of Managed Care^®, MINT trial principal investigator Richard J. Nowak, MD, MS, explains inebilizumab’s mechanism of action and how the 52-week data build on 26-week patient-reported outcomes. Nowak is an associate professor of neurology at the Yale School of Medicine, where he is also director of the myasthenia gravis clinic and the program for clinical and translational neuromuscular research. He presented the newest data in a late-breaking session today at the 2025 American Academy of Neurology annual meeting.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

How does inebilizumab work at treating MG?

Inebilizumab is the medication that we studied in the Myasthenia Gravis Inebilizumab Trial, or MINT. The reason why we studied inebilizumab is that it is an anti–CD19 B-cell–depleting therapy. Why is that important? B cells are the factories of antibody production, and they're also the factories of pathogenic autoantibody production. In approximately 80% of patients with generalized myasthenia gravis, there's a mistake that certain B cells make, where they produce acetylcholine receptor autoantibodies, and that attacks the surface of the muscle, causing disease, specifically the weakness that we see. In another 5% to maybe up to 10% of patients, the B cells make a different autoantibody called MuSK.

Out of all generalized patients, I would say [that in] maybe 85% to upwards of 90%, they have 1 of these 2 autoantibodies. Inebilizumab is unique in that it can target specific B cells that are producing antibodies, antibody-secreting cells. Not to get into too much of the weeds of this, those are typically what are termed plasma blasts and long-lived plasma cells.

There are other ways that we can target B cells, but inebilizumab is unique in that it's able to target B cells that are specifically producing autoantibodies that are causing disease. The way that I look at this is, inebilizumab can attack, or target, the factories of antibody production, which is really important. There are antibodies floating around, and you're not directly targeting the factories that are making them; you're really not directly treating the condition.

What do the 52-week data from the MINT trial reveal?

This was a phase 3 placebo-controlled clinical trial that included both placed acetylcholine receptor– and muscle-specific kinase antibody–positive generalized myasthenia gravis patients. We enrolled a total of 238 patients. Of those, 190 were AChR positive and the other 48 were MuSK positive.

The initial prespecified primary end point was change in MG-ADL as compared to baseline at week 26 for all patients in the randomized control period. We demonstrated a significant reduction in the MG-ADL score as compared to the baseline group. The study met its primary outcome measure, demonstrating clinically meaningful improvements in the patient-reported outcomes. We also, as a key secondary end point, looked at change in baseline to week 26 in the QMG score. This is a physician-reported outcome measure that essentially measures muscle strength and fatigability of muscles and that also demonstrated a significant reduction in QMG score as compared to baseline. Both the primary end point and the key secondary end point of the study met statistical significance.

The AChR-positive group, the randomized control period for that subtype, extended through 52 weeks. What we're presenting at the 2025 AAN late-breaking session [are] data on the 52-week follow-up from our patients with AChR that completed the randomized control period. Similarly to what we observed at week 26 in the combined population, we're also seeing a statistically significant reduction in MG-ADL score in the treatment arm as compared to placebo. We also see that in the QMG. We also are presenting data that looked at the proportion of individuals that achieve a 3- or greater point improvement in MG-ADL and QMG scores at week 52, and the proportion of patients is significantly larger as compared to placebo.

The 52-week data are in support of efficacy and also the durability of response for our patients treated with inebilizumab. Also, if you look very carefully at the data and at the numbers, there appears to be further improvement in the ADL and QMG scores as time goes [on]—so the depth of response appears to be a bit greater if you compared week 26 to week 52, but we certainly do need to do additional analysis and a more careful understanding of the data.