Current standard of care for C3G

Video

Carla M. Nester, MD, MSA, FASN discusses the current therapeutic area for C3G and what is on the horizon.

Jonathan Barratt, PhD, FRCP: If we think about what's happening in the therapeutic arena, Carla, I want you to talk us through where we are now with C3G or perhaps where we are not, and what are the opportunities you see on the horizon in terms of the clinical trials and therapeutic approaches that are being evaluated.

Carla M. Nester, MD, MSA, FASN: For C3 glomerulopathy, there are no clinical trials, randomized controlled trials that we can rely on to currently treat these patients. According to the most recent clinical guidelines, which are the KDIGO guidelines, we are supposed to attempt supportive cares, which in fact makes perfect sense. We should be controlling the blood pressure, we should be controlling the lipids, we should be controlling salt intake, et cetera, whatever the appropriate dietary things are. Let's face it, for an aggressive glomerular disease, they're not going to be the answer for most patients, but we should still start there. Then after the supportive care comes into play, if patients continue to have very significant glomerular diseases, and that's classically a suggestion of greater than a gram of protein persists, we should be thinking about immune suppression. Right now, again, based on retrospective studies, there's about 9, 10 reports out there that would suggest that mycophenolate mofetil and corticosteroids in combination will bring remission for some patients. I will tell you; it absolutely does work in some patients. Back to your idea of biomarkers, we don't know which patients it's going to work in, but it does work for some. It is important to supportive care and then consider the mycophenolate mofetil and the corticosteroids. After that and again, depending on which cohort you like to accept the data on, the response is anywhere from 30% to 75% with that sort of series of attempts to put these patients in remission. Then we will be thinking about terminal complement blockade. Even the data for terminal complement blockade, again, I mentioned earlier in my pathophysiology discussion, we believe that in the case of C3 glomerulopathy, the disease is driven upstream, not at the terminal pathway level. Now, patients can get a benefit because if you have a very active upstream, you have a lot of anaphylatoxins floating in the circulation, particularly C5A, for instance. It does make sense to potentially block C5A or block C5 so that you have been blocked C5A, but the published data is not terribly much better for terminal complement block A than it is for mycophenolate mofetil and corticosteroids. Even though everything we've got to try has been tried and has been reported reasonably well, I would still say we're stuck with a disease that doesn't have a really targeted therapeutic approach.

Jonathan Barratt, PhD, FRCP: I guess the MMF prednisolone is directed at auto-antibody production or an inflammation within the kidneys.

Carla M. Nester, MD, MSA, FASN: I believe it's probably both. We have not been able to document that the nephritic factors, the autoantibodies have declined as a result of that approach. But to be fair, no one's looking that tightly at that to really understand whether that's happening but that's what we suspect might be happening. It's also probably an anti-proliferative approach so if you have a lot of circulating anaphylatoxins, perhaps blocking your own immune system response to those anaphylatoxins can be beneficial to the kidney. That's the theory behind how they may work for some patients.

Transcript Edited for Clarity

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