Novartis and Apellis Pharmaceuticals have rolled out detailed data on iptacopan and pegcetacoplan, respectively, as they race for the prize in a type of rare kidney disease.
Saturday, Apellis laid out full phase 3 results on its Sobi-partnered C3 therapy pegcetacoplan, showing the drug passed muster across primary and secondary endpoints in patients with the debilitating kidney diseases C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).
Pegcetacoplan is already approved in paroxysmal nocturnal hemoglobinuria (PNH) and geographic atrophy (GA) under the brand names Empaveli and Syfovre, respectively.
Two days after Apellis’ data drop, Novartis rolled out its own set of positive C3G results for its drug iptacopan, which goes by the commercial moniker Fabhalta in PNH and primary IgA nephropathy (IgAN).
While cross-trial comparisons carry inherent flaws, the data seem to favor Apellis and Sobi’s drug on key kidney disease metrics like reduction in the level of protein in the urine (proteinuria). Nevertheless, Novartis appears to have gotten a head start on the path to potential approvals.
The Swiss pharma has already sent off regulatory submissions for the potential new Fabhalta indication in Europe, China and Japan, and it plans to file in the U.S. before the end of the year, the company said in a Sunday release.
Apellis, for its part, says it plans to file its pegcetacoplan application at the FDA in “early 2025,” with Sobi expected to submit a marketing bid with the European Medicines Agency later next year.
Taking a closer look at the data, Apellis’ pegcetacoplan led to a statistically significant and clinically meaningful 68.1% proteinuria reduction at the 24-week mark in the late-stage VALIANT study, which pitted the company’s C3 med plus standard care against placebo and standard care treatment.
Proteinuria reductions were seen as early as week 4 and continued through the six-month treatment period, the company said. Additionally, reductions were consistent across patients with C3G and IC-MPGN, as well as in kids and adults and those who had and had not received kidney transplants.
Those results track with topline data on pegcetacoplan that Apellis and Sobi unveiled in early August.
New to the medicine’s data package, Apellis showed that pegcetacoplan achieved stabilization of estimated glomerular filtration rate (eGFR)—a key measure of kidney function—over six months versus placebo.
Further, 74.3% of patients on pegcetacoplan achieved a reduction in C3c staining intensity by two or more orders of magnitude from baseline, versus just 11.8% of patients the trial’s control cohort. C3c is a fragment of the protein complement component 3, or C3, which is implicated in the body’s immune system. Excess C3c deposits are a key marker of disease activity and can lead to kidney inflammation, damage or failure, Apellis said.
“We are thrilled by these results, which underscore the potential for pegcetacoplan to significantly improve patients’ lives by directly targeting C3, the underlying cause of C3G and IC-MPGN,” Apellis’ chief medical advisor for rare diseases, Peter Hillmen, Ph.D., said in a statement.
Apellis’ trial favored pegcetacoplan on all secondary endpoints, too, the company said.
Over on Novartis’ side of the fence, two daily doses of oral Fabhalta led to clinically meaningful proteinuria reductions, which started as early 14 days into treatment and were sustained over a year, the company said.
In an open-label period of the phase 3 study, coded APPEAR-C3G, proteinuria reductions were also witnessed in patients who switched over to Novartis’ drug from another treatment.
Fabhalta also triggered an improvement in eGFR upon treatment start versus “patients’ historic rapid decline” based on results from a prespecified exploratory analysis, Novartis explained.
Unlike Apellis’ study, which enrolled patients ages 12 and up, Novartis only recruited adults for its trial. APPEAR-C3G consisted of an initial 6-month treatment period followed by another 6-month open-label treatment period where all participants received Fabhalta.
Novartis previously revealed that Fabhalta yielded 35.1% proteinuria reduction compared to placebo on top of supportive care at the trial’s six-month mark.
Both Apellis’ and Novartis’ drugs were generally safe and well-tolerated in their respective trials, the companies said.
As it stands, there are no available treatments that target the underlying cause of C3G and IC-MPGN, Apellis noted in its release. Approximately 50% of people living with the rare and devastating kidney diseases suffer from kidney failure within five to 10 years of diagnosis, prompting the need for kidney transplant or lifelong dialysis.
Apellis estimates the diseases affect a combined 5,000 people in the U.S. and up to 8,000 people in Europe.
Earlier this year, when Apellis rolled out topline results on pegcetacoplan in the kidney disease pair, analysts at Evercore ISI cited the drug’s “enormous efficacy” in influencing their prediction that it could win a majority future market share. At the time, the Evercore team branded the rare kidney disease space a potential “blockbuster opportunity.”