Andrew Bomback, MD, Columbia University Medical Center, discusses the Phase 2 NOBLE study, testing pegcetacoplan in patients with immune-complex MPGN or C3 glomerulopathy.
Transcription:
The NOBLE study is a really interesting study because what it’s looking at is recurrent forms of immune-complex MPGN and C3 glomerulopathy in transplanted kidneys. We know from natural history studies, including some that I did at Columbia but have been done around the world, that patients with C3 glomerulopathy and immune-complex MPGN who reach end stage kidney disease and undergo transplantation, have a very high rate of disease recurrence in their transplanted kidney, what we call the allograft kidney.
What the NOBLE study does is use pegcetacoplan, a C3 inhibitor that’s directly targeting C3 to address this recurrent disease. It’s a really fascinating study, in my opinion, because the enrollment criteria for this study turned out to be just the appearance of the disease on a kidney biopsy. So we are catching many of these patients very early when the disease recurs, where the disease may not be incredibly manifest clinically, but we know it’s going to evolve into something very dangerous for the transplanted kidney if it doesn’t stop.
And so by enrolling these patients with recurrent forms of C3 glomerulopathy and immune-complex MPGN that’s seen very clearly on a biopsy of the transplanted kidney, and then giving them pegcetacoplan for 12 weeks in the part of the study that we’re presenting at ASN, and then in the follow-up study— the treatment is going to be extended out to a year, and that data at a year is not available yet, but we’re presenting the 12-week data—we’re looking to see how early intervention with a complement targeting drug here, a C3 inhibiting drug, can potentially turn off the disease at its earliest state.
It’s a very promising result from this study. The outcome was looking at changes in the intensity of C3 staining on the biopsy at 12 weeks. We have 10 patients who were given the drug for 12 weeks, and we’re comparing them to three patients who were not given the drug. I’m really going to focus on the 10 who got the drug.
What was really exciting is that most of those patients had significant drops in C3 staining on the biopsy. Remember, the way we diagnose this disease, especially in the early stage, is by the intensity and the presence of those C3 deposits. When we see patients who, in just 12 weeks, either reduce the intensity of their C3 staining, or in some cases, actually completely lose their C3 staining, we have really nice, and what I think is objective evidence from repeat biopsies to say that we’re impacting and modifying the disease course. That we’re actually turning off the disease potentially by stopping the deposition of C3 breakdown products on these kidney biopsies.
And to do so at 12 weeks is really exciting because that’s such an early time point to look at changes. What it suggests to me is that this drug is acting very fast and very effectively, and I’m so excited to see what the one-year results are going to be when we finally get that readout.
To learn more: https://checkrare.com/diseases/kidney-and-urinary-diseases/
