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Updates in the Management of Myasthenia Gravis Peers and Perspectives - Episode 11

Complement Inhibitors

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Experts discuss the benefits of complement inhibitors in reducing symptoms of myasthenia gravis.

Dr. James F. Howard: And so, you've had clinical trial experience with each of these or many of these. What's your experience been with complement inhibitors?

Dr. Nicholas J. Silvestri: With complement inhibitors, my experience has been thus far very good in clinical practice. The complement inhibitors, specifically eculizumab, have been very good. Patients that were at times quite severely affected by their disease, who hadn't responded to other therapies, who had intolerable side effects in other therapies have really done quite well with the complement inhibitors or eculizumab specifically. Bringing people from frequent hospitalizations, poor quality of life to minimal symptoms. It's been from a clinical standpoint, quite nice addition to the armamentarium.

Dr. James F. Howard: Yeah, we've had similar experience in responses eculizumab. It's restricted in its use. Though the FDA approved it for generalized AChR positive myasthenia, the payer community has restricted it to refractory myasthenia and each has their own definition. Many of them following the clinical trial definition of failing at least two drugs over the course of the year or one, but requiring plasma exchange or IVIG. But what has been an interesting observation is that at the end of the 26-week period, about 60% of the folks improved substantially. And as you follow them over the course of 130 weeks, increasing numbers approved, increasing numbers achieved minimal manifestations. Very surprisingly so. 85%, 90% at the end of 130 weeks were better. Some 60%-plus achieved minimal manifestations. And these were folks who had disease duration of 10-plus years who had moderate to severe generalized weakness who had failed multiple therapies. Some of them been on at least three ISTs over the course of their treatment, and yet still had the capability of getting better, which to me implies that the neuromuscular junction isn't so static, and it may be able to rebuild and repair itself once we take away this architectural destruction. We've had similar benefit with ravulizumab. We were involved in the trial and in those patients responded just as nicely. That trial was open to any myasthenic patient. There was no restriction in terms of failure to respond to treatment. And so, with its approval, the hope is that we’ll be able to use it in a broader population of patients. And zylupaplan, the subcutaneously administered product, that trial is also using all comers if you will. With some people with disease duration, as short as a couple three, four months and still a derived benefit. I think complement inhibitors are going to play a big role going forth as one of our new targeted therapies.

Transcript Edited for Clarity