Novartis and its Fabhalta may have been first to the punch in ultrarare kidney disease complement 3 glomerulopathy (C3G), but Apellis Pharmaceuticals has delivered a checkmate with a wider label and a double approval for its Sobi-partnered Empaveli.
Empaveli (pegcetacoplan) won FDA clearance to treat both C3G and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), another rare and severe kidney disease for which Empaveli is the first approved treatment. Importantly, Empaveli’s label covers adolescents as well as adults.
The FDA signed off on the drug based on a phase 3 study that tested Empaveli in a broad group of patients in both rare diseases. In the trial, dubbed VALIANT, Empaveli hit on a key “trifecta” of kidney-disease-related measures, Apellis’ co-founder and CEO Cedric Francois, M.D., told Fierce Pharma in a recent interview.
The trio of endpoints comprises proteinuria reduction, stabilization of kidney function and reduction of C3c staining. Compared with placebo, Empaveli led to a 68% reduction in patients' proteinuria (protein in the urine) at Week 26. Results were consistent across age groups and among patients with native or post-transplant kidney status in both diseases. Plus, a “substantial proportion” of Empaveli-treated patients showed a reduction in C3c staining intensity, while 71% achieved complete clearance of C3c staining over placebo, another key disease indicator.
Empaveli’s performance in the VALIANT study confirmed the drug’s “enormous efficacy,” giving analysts at Evercore ISI reason to declare the med a “blockbuster opportunity,” the analysts wrote in a note after Apellis’ readout last summer. Apellis, too, has lauded the drug’s blockbuster potential.
The drug’s mechanism of action is “where the magic lies,” Francois noted. Pegcetacoplan is a targeted C3 therapy meant to regulate excessive activation of the immune system’s complement cascade.
C3G and primary IC-MPGN can cause severe outcomes, with about half of patients suffering from kidney failure within five to 10 years of diagnosis, requiring a kidney transplant or lifelong dialysis. Approximately 90% of patients who receive a kidney transplant will experience disease recurrence, according to Apellis. The diseases impact an estimated 5,000 people in the U.S. and 8,000 in Europe.
Empaveli won’t be first to the C3G field thanks to Novartis’s Fabhalta, but it will be the first to market in IC-MPGN. Fabhalta is limited to adult C3G patients, while Empaveli’s label applies to adolescents as well. Apellis also tested its drug in post-kidney transplant C3G patients, while Novartis did not. The two drugs already compete in the paroxysmal nocturnal hemoglobinuria (PNH) market.
In one disappointment, Empaveli’s latest label also specified that the drug is meant to reduce proteinuria rather than just treatment of C3G, for which kidney function benefits are the ultimate goal. Still, the Empaveli label includes a line that says the drug reduced the loss of kidney function compared to placebo over the first six months of treatment.
According to the company, the inclusion of the primary endpoint in the indication is "standard practice" for the FDA's cardiology nephrology division, a spokesperson said.
Apellis has long been preparing to serve the “incredible need” in the disease area with Empaveli and is ready to make an “enormous difference” in the lives of patients, Francois said. The company has already “thoroughly expanded” its team to bring in experts in kidney care, and about 70% of U.S. patients with the two diseases are seen in the same care centers as Empaveli’s existing patients for its PNH indication, according to the CEO.
Growth to come for Apellis
With now three approvals in four years, Apellis has come a long way from its beginnings of what Francois describes as a “scrappy three-man laboratory” in Kentucky. The 16-year-old company followed up on Empaveli’s original 2021 PNH approval with Syfovre, an injectable version of pegcetacoplan that hit the U.S. market in 2023 as a geographic atrophy treatment.
“We are hoping to discover a lot more growth in the years to come,” Francois said. The CEO considers both Empaveli and Syfovre to be “on a potential path to blockbuster status.”
Citi Research analysts have already pegged their expectations for the new approvals to “transform” the Empaveli franchise, given its “best-in-class efficacy” in the disease areas, the analysts predicted in a May note to clients.
Last year, Empaveli and its eye health counterpart helped Apellis pull $781.4 million in full-year revenues, although Syfovre delivered the lion’s share of those earnings.