乌鸦传媒

Data from the randomized MINT trial, presented at the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) annual meeting, showed that the anti-CD19 monoclonal antibody inebilizumab (Uplizna) for generalized myasthenia gravis improved disease severity, reduced steroid burden, and had a good safety profile.

In this exclusive 乌鸦传媒 video, Richard Nowak, MD, of the Yale Myasthenia Gravis Clinic in New Haven, Connecticut, discusses the significance of the phase III study.

Following is a transcript of his remarks:

So number one, represents one of the largest-to-date registrational clinical trials, enrolling the largest study population, including the largest MuSK [muscle-specific kinase] study population in a prospective longitudinal manner.

Number two, in addition to demonstrating both safety and efficacy based on our primary endpoint and our key secondary outcomes, the study also included a prespecified steroid dose reduction. So all patients that enrolled in our study that were on prednisone or corticosteroids were required to reduce their dose over time. So not only is MINT demonstrating there is clinical efficacy and safety, but also it's demonstrating a reduced burden of steroids along with the safety and efficacy data that we have.

So this is super exciting and does speak to the ability not only that inebilizumab is clinically beneficial, but also that we can actually successfully reduce the burden of corticosteroids in our patients with generalized myasthenia gravis.

What's critically important, especially as we have more and more available options for the treatment of myasthenia gravis -- specifically generalized myasthenia gravis -- is that there are different mechanisms of action by which the medications work. Inebilizumab represents the first-in-class potential anti-CD19 B-cell depleting therapy strategy, which contrasts with the currently available treatment options that have been recently FDA approved, such as the [neonatal Fc receptor] antagonists, as well as the C5 complement inhibitors.

So this is especially important in particular for individuals that are not responding or inadequately responding to conventional or available therapy options for them. No clinical trial that has been completed to date has demonstrated efficacy in every single individual studied or on active drug. So it's important for us to have therapy options.

The other important piece to understand is that inebilizumab works upstream on the upstream immune pathogenesis of disease-targeting select B cells that express a CD19 antigen on their cell surface. And you might ask, why is that important? Well, it's important because antibody-secreting cells, including autoantibody-secreting cells, actually have CD19-positive B cells as their profile. So we're really targeting the antibody-secreting cells in those that are producing pathogenic autoantibodies with an anti-CD19 directed B-cell depletion therapy.

The study achieved its initial goal, which was to demonstrate safety [and] tolerability along with clinically meaningful efficacy, and what we shared at the most recent AANEM this month, October of 2024, was our topline study results and findings. Additional statistical analysis and understanding of the data is our next step, and our next steps also include preparation and publication of our topline results in the primary study manuscript.

I think that as we learn more about the findings of MINT and the nuances contained in the study, this is something that is extremely exciting. Again, I'll note that inebilizumab is not FDA approved for generalized myasthenia gravis, but based on the strong findings of safety and efficacy, it's something that in future makes potential good sense and is a rationale treatment strategy option for our patients.

So what it does is it provides evidence for the role and importance of B cells and targeting those B cells in treatment for myasthenia gravis, particularly those with both or either [acetylcholine receptor] or MuSK autoantibodies.

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