Targeting the Root of gMG With Inebilizumab: A Q&A With Richard Nowak, MD, MS

Data out to 52 weeks from the MINT trial (NCT04524273) highlight the potential of inebilizumab, a CD19-directed B-cell–depleting therapy, as an effective treatment for generalized myasthenia gravis (gMG) in patients who are acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) antibody-positive. The phase 3, placebo-controlled study met its primary end point at 26 weeks, demonstrating clinically meaningful reductions in Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, with sustained benefits seen at 52 weeks in the AChR-positive cohort. Quantitative Myasthenia Gravis (QMG) scores, which assess muscle strength and fatigability, also showed statistically significant improvements.

In this interview with Richard J. Nowak, MD, MS, principal investigator of the MINT trial, he discusses the trial’s key findings, including significant improvements in both patient-reported and physician-assessed outcomes, as well as the durability of response observed in the AChR-positive subgroup through 1 year of treatment. He also emphasizes the importance of early symptom recognition in MG—particularly ocular symptoms—which can often precede generalized weakness and explores the mechanism of action of inebilizumab, its clinical efficacy, and the implications of these findings for future MG treatment strategies.

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 these topline data, through week 52, at the 2025 American Academy of Neurology (AAN) annual meeting.

This transcript has been lightly edited for clarity.

Richard J. Nowak, MD, MS | Image Credit: Yale School of Medicine

The American Journal of Managed Care® (AJMC®): How does inebilizumab work at treating MG?

Nowak: Inebilizumab is the medication that we studied in the MINT trial. 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 gMG, there's a mistake that certain B cells make, where they produce AChR 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. 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.

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

Nowak: This was a phase 3 placebo-controlled clinical trial that included both patients with AChR– and MuSK antibody–positive gMG. We enrolled 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 compared with baseline at week 26 for all patients in the randomized control period. We demonstrated a significant reduction in the MG-ADL score compared with the baseline group. The study met its primary outcome measure, demonstrating clinically meaningful improvements in the patient-reported outcomes. As a key secondary end point, we also looked at [the] change [from] 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 compared with baseline. Both the primary end point and the key secondary end point of the study were statistically significant.

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

The 52-week data are in support of efficacy and 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—so the depth of response appears to be a bit greater if you compare week 26 to week 52. But we certainly do need to do additional analysis and [gain] a more careful understanding of the data.

AJMC: Are there early in-common symptoms among patients who have MG?

Nowak: It is an autoimmune condition that affects neuromuscular transmission. The clinical symptoms that we see are fatigable muscle weakness. Most commonly, in fact, in up to 90% of individuals, the first presenting symptom is an ocular symptom—double vision or eyelid droop or [a] combination of both. We observe that in most patients, regardless of the antibody subtype that they might have. Patients in about 50% to 75% of cases will progress to a generalized form of MG. This can include things like difficulty speaking, so slurred speech, fatigue with chewing, choking on food, and also weakness in their arms and legs are not uncommon symptoms that we observe.

AJMC: How can identifying these early symptoms help guide future research efforts?

Nowak: I think early recognition and early diagnosis is something that we do need to pay attention to. It has been observed over the years that there can be a delay to diagnosis of up to 2 or so years from the initial symptom, looking retrospectively back. I think that's certainly much more common in individuals who present with milder symptoms or subtle symptoms, where the symptoms might fluctuate—so that by the time they might reach their physician, primary care [doctor], or ophthalmologist, for instance, in the case of double vision, the symptoms and exam findings might have completely resolved, so an evaluation might not necessarily be pursued. MG, as a rare condition, is not the first thing that comes to mind when someone might have double vision or eyelid droop, per se, but it certainly should be on the radar of physicians in primary care, ophthalmology, or in neurology for sure.

AJMC: What steps are being taken to assess long-term safety and tolerability of inebilizumab in AChR-positive gMG beyond the 52-week period?

Nowak: MINT included an open-label extension period of up to 3 years,and study participants had the opportunity to enroll in that open-label extension portion. That part of the trial is still underway and ongoing, so we continue to follow patients for up to that 3-year mark. What we've presented at week 26 and week 52 are data that we have up until this time, but we certainly have patients who remain in [the] study where we're collecting safety and tolerability data. Initial analysis of safety and tolerability during the randomized control period does not show any concerning safety issues or safety signals. The analysis is more or less in line with what's been published and available in neuromyelitis optica spectrum disorder. What we have so far is a demonstration of safety and tolerability as assessed to date in patients who have gMG.

AJMC: How do demographic factors—for example, age and gender—affect efficacy and safety outcomes?

Nowak: We don't have any data that would suggest that any particular age group or antibody subtype, for instance, or any race or ethnicity factors impact safety or efficacy. Looking at the population of patients with gMG in the study, it really matches a gMG population. Patients were in their late 40s, for instance; the male:female breakdown was well matched in the treated group compared with placebo; and the groups were well matched. We don't have any early indicators that any of those factors would impact, for instance, safety and efficacy—or durability of response at this point.

AJMC: Looking at the full data set, is there anything these results don't address that you are still curious about?

Nowak: We're still in the process of analyzing the data and exploring the data further. There are additional secondary and exploratory analyses underway, which will focus on things like risk of myasthenia gravis exacerbation requiring rescue therapy, health care resource utilization, for instance; that durability of response that we talked about in terms of how long-lasting the effect is; and do patients potentially continue to show improvement the longer they are on the medication over time? There are a number of things that we most certainly are planning to look at as we have additional data available for analyses. What we're presenting to date is our prespecified topline results, the primary and key secondary [outcomes data] as well as now, very excitingly, the through–week 52 data on the AChR-positive cohort, which are extremely encouraging.