Pegcetacoplan Offers Promising New Treatment Approach for Patients Aged 12 and Older With C3G, Primary IC-MPGN: Carla Nester, MD, MSA, FASN

On Monday, the FDA approved pegcetacoplan (EMPAVELI; Apellis Pharmaceuticals) as the first treatment for patients aged 12 and older with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), 2 rare and severe kidney diseases. The approval is supported by data from the phase 3 VALIANT trial (NCT05067127).

In this clip, Carla Nester, MD, MSA, FASN, lead principal investigator of the VALIANT trial and director of pediatric nephrology at the University of Iowa Stead Family Children's Hospital, discusses the trial's findings and describes how pegcetacoplan is reshaping the treatment landscape, especially for pediatric patients.

Transcript

Can you summarize the key findings of the VALIANT trial and how they supported the FDA's approval of pegcetacoplan for patients aged 12 and older with C3G and primary IC-MPGN?

The VALIANT trial was a 26-week placebo-controlled study for the drug pegcetacoplan. The really exciting part about it is that they met their primary end point. Just very quickly, the primary end point was that of proteinuria reduction specifically. In that 26-week trial, they saw a 68% reduction in proteinuria in the treated group, so that was amazing. I mean, from a clinician's standpoint, that's exactly the type of thing that we want to see.

Then, they had a few secondary end points, which are also incredibly important to a clinician. One of them is the stabilization of the GFR [glomerular filtration rate]. We classify this disease as one of those diseases that just regularly lose kidney function over time. Your readers may know that these patients, 50% of them, lose their kidney function, or they go to end-stage within 10 years. Now, suddenly, in this trial, we see that not only do they not have that slope downward like what they did naturally, but now even we've got an improvement. At the 26-week mark, they actually saw a positive 6.3 mL of GFR, if you will.

Finally, as a complementologist, one of the most exciting things for me was when they looked at the kidney biopsy of the adult group. I didn't share with you that this was an adult and pediatric study. When they looked specifically at the adult group, what they saw was that up to 71% of the patients actually lost the C3 deposition on the biopsy. The really amazing piece for a clinician is that the animal models suggested that the disease was done. I'll stop short of saying cure, but I mean, that's a really exciting finding, that you're losing the diagnostic criteria of the disease and you no longer have that C3 deposition.

How would you describe the current standard of care for C3G and primary IC-MPGN, and what does pegcetacoplan add to the treatment landscape?

The treatment, prior to the availability of alternative pathway blockades such as a pegcetacoplan, was really what we would call a more generic immune suppression. It included mycophenolate mofetil, it included prednisone, etc., and, of course, some supportive care.

The problem is that, first of all, all of your patients will know that prednisone carries a number of [adverse] effects that are quite unpleasant for them, but also, even more important to the clinician is that only about 30% of all comers, if you will, responded to this regimen. We have a disease that just kept right on marching to end stage for many patients despite the current standard of care, so that's the background.

Then, if you sort of fast-forward to agents such as pegcetacoplan, now we can target the alternative pathway, which is the underlying cause of this disease. Now, we can target the alternative pathway; we can use pegcetacoplan. Now, in theory, again, we get back to this issue of, can we now stop the disease in its tracks? Can we now treat patients safely but also much, much more efficaciously than we could have previously?

Given the limited treatment options, what does this approval mean specifically for pediatric patients living with these rare kidney diseases?

The exciting thing about the pegcetacoplan approval is that it's the first phase 3 [data] available to the FDA that supports the use of a medication in the pediatric population. Now, the global cohorts are maybe just a little bit different in the median age, but generally it's the 16-year-old.

We needed to be able to get access down. In fact, I'm going to advocate for us getting even lower, but we needed to get down to at least the age of 12, because that's when the median age of the patient is. This will be my first opportunity to actually treat the group of patients [in whom] the bulk of this disease is being expressed in.