Analyzing Inebilizumab’s Durable Benefit in MINT Open-Label Extension

Inebilizumab is a first-in-class anti-CD19 B cell depleting monoclonal antibody evaluated in generalized myasthenia gravis (gMG) in the phase 3 MG Inebilizumab Trial (MINT). The trial enrolled patients with anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive disease and met its primary and key secondary end points at week 26, with significantly greater improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores than placebo.¹

New findings from the open-label period were presented at the 2026 American Association of Neuromuscular and Electrodiagnostic Medicine Annual Meeting. In an analysis of the MuSK+ subgroup, 48 participants were randomized, 46 entered the open-label period, and 44 completed 26 weeks of it. By week 52, MG-ADL and QMG scores had continued to fall from baseline in both the inebilizumab-only group (–5.6 and –6.1) and the group that switched from placebo to inebilizumab (–5.1 and –7.4).

NeurologyLive^® spoke with Richard Nowak, MD, director of the Yale Myasthenia Gravis Clinic at Yale University and global principal investigator of MINT, who presented the data at the meeting. Nowak answered questions on the durability and safety of response in the extension, other MINT analyses presented including disease duration, what has been learned about using inebilizumab in practice, and how myasthenia gravis trials can evolve.

NeurologyLive: You’re presenting a few different analyses here at AANEM, mainly the open-label extension data. For our clinical audience, can you provide some background on the 26-week open-label extension data being presented, what the data show, and some of your takeaways?

Richard Nowak, MD: MINT, the Myasthenia Gravis Inebilizumab Trial, was a phase 3 clinical trial that enrolled patients with either AChR or MuSK autoantibody positive generalized myasthenia gravis. Its primary outcome measure was met, which looked at the change from baseline in MG-ADL score in the treated group vs those assigned to placebo.

The key secondary outcome measure was also met, showing a difference in QMG between those who received treatment and those assigned to placebo. The primary study results led to FDA approval of inebilizumab for patients with generalized myasthenia gravis who are either AChR or MuSK autoantibody positive in December 2025.

As part of that trial, we also had an open-label extension of up to 3 years that patients who completed the randomized controlled period were able to enroll in. We felt it was important to take a data cut at 1 year, looking at how patients were doing 1 year after enrolling in the open-label extension. What we observed is that patients continued to have a durable response in their MG-ADL score and in their QMG score, which is a physician-reported outcome measure. In fact, patients who were initially assigned to placebo saw their scores improve once they were treated with inebilizumab in the open-label extension period.

So, what are we learning from the data? The first thing is that the response is durable and sustained 1 year further out in the study period, and that patients have a greater depth of response compared with the initial randomized controlled period. These are very encouraging results from the open-label extension, and this was observed in both the AChR subpopulation and the MuSK autoantibody subpopulation.

What did safety show over this extension period, and what have you seen so far?

One question that comes up is the safety and tolerability profile of any medication, including inebilizumab. Safety and tolerability were observed for an additional year of follow-up during the open-label extension. I will add that the open-label extension is ongoing, and we will be following patients for up to 3 years, so additional data are to come.

But we presented this data cut because we wanted to show that patients had continued benefit and to comment on the safety. Again, safety and tolerability were consistent with the randomized controlled period and with the other indications for which inebilizumab is currently approved.

There were other presentations on MINT beyond the open-label extension. What other data were presented here, and what else did we learn from this trial?

One question that comes up is whether treatment response depends on disease duration before treatment is initiated. That has come up not only for inebilizumab but for some of the other medications currently available. We took a deeper dive and looked at patients with disease for less than 1 year, between 1 and less than 4 years, and 4 years or more. We looked at the depth of response, specifically the MG-ADL scores from baseline to week 26, so this is the randomized controlled period.

We observed greater improvements in all of those disease duration subgroups compared with placebo. It is a post hoc analysis, so we could not apply statistical analysis to it, and definitive conclusions cannot be made. But it was nice to see that greater improvements continued in each of those subgroups compared with the placebo groups.

Inebilizumab was first approved for NMOSD a couple of years ago and gained approval for myasthenia gravis last year. What have we learned about how to optimize the way we use this drug, in clinical trials and in the real world, and how confident are we in this mechanism?

B cells, and disrupted B cells, are central to autoimmune myasthenia gravis, and targeting those cells, the factories of autoantibody production, remains key as I see it. Inebilizumab allows us to do that. The reliability of response from targeting pathogenic autoantibody-secreting B cells does translate into clinical benefit, as we demonstrated in the randomized controlled period and during the open-label extension. The mechanism of action, as I noted before, is first-in-class anti-CD19 B cell depletion therapy.

What we have additionally learned, by design based on our protocol, is that participants in MINT were able to lower their corticosteroid or prednisone dose from the time of initiation to completion of the randomized controlled period.

What we are observing in clinical practice, and this is anecdotal, is that for patients we treat with inebilizumab, we follow a similar steroid reduction schedule as was done in MINT, and at least anecdotally, we are seeing similar responses. Patients are able to reduce their corticosteroid doses and are having clinical benefits.

As someone so involved in phase 3 trials in myasthenia gravis, what else do we need to do to continue to optimize myasthenia gravis trials over the next 5 to 10 years?

Myasthenia gravis clinical trials in the modern era have followed a very similar approach: looking at a patient-reported clinical outcome, specifically the MG-ADL score, and comparing the treatment group with those assigned to placebo, essentially looking for a difference. We have also looked at physician-reported outcome measures like the QMG, which is basically an examination to look for improvements.

Those have typically been the primary and secondary outcome measures for many, if not nearly all, MG clinical trials. In trials that have led to FDA approval, the patient-reported outcome measure, at least to date, has been required by the FDA as the primary outcome measure.

There are certainly learnings from these trials in terms of further optimizing the outcomes over time. One thing that is sometimes missing from simply looking at score changes is a better picture, some additional color, for each patient on a patient level. That includes things like health care resource utilization. In MINT, as part of our secondary analysis, we looked at exacerbation rate, hospitalization, and time to achieving a certain prespecified outcome.

One thing that has gained attention in recent years is minimal symptom expression, which is defined as an MG-ADL score of either 0 or 1. Again, this is patient reported, but it looks at the ability to achieve that and how long it takes, essentially whether the patient is symptom free based on their own report.

Will our outcomes change for clinical trials? That is a tough bar to cross when there is precedent for doing trials and looking at outcomes the way we have been. I will say there are certainly limitations in the data we gather from these trials, and they don’t paint a personalized patient picture. One thing we haven’t really learned, with all of these medications available, is that there is a subgroup of individuals who don’t have a good response or any response, and we don’t understand why.

In addition to the traditional outcomes, which are established and validated for the study of myasthenia, we should complement them with other clinical outcome measures. Second, we should likely complement them with true biomarkers or mechanistic studies that teach us about the disease and help predict which patients will respond well, less well, or not at all to certain drugs.

The holy grail of autoimmunity is the induction of self-tolerance. As a forward statement, 5 to 10 years from now the goal would be to achieve self-tolerance. I think that is feasible in autoimmune myasthenia gravis, where we know the antibodies and the target in the vast majority of patients, but for all autoimmunity, achieving tolerance is the holy grail. We are one step closer, I think, but there are many more steps to go.

Transcript edited for clarity. For more AANEM 2026 coverage, click here.