While Apellis Pharmaceuticals has spent much of the year working around setbacks that derailed the ongoing launch of its geographic atrophy (GA) drug Syfovre, a major phase 3 triumph could open up a new market for the drugmaker.
The company’s Sobi-partnered pegcetacoplan, which is branded as Empaveli for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), scored in a phase 3 study of patients with C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), two rare kidney diseases.
Compared with placebo, Empaveli led to a 68% reduction in patients' proteinuria (protein in the urine) at Week 26, the companies reported. The results were consistent across age groups and among patients with native or post-transplant kidney status in both diseases, they said.
Besides success on the primary endpoint, the trial, dubbed VALIANT, also met some secondary endpoints, including a composite metric that combined proteinuria reductions and estimated glomerular filtration rate stabilization.
Elevated levels of proteinuria are associated with serious kidney issues. In another disease, IgA nephropathy, reductions in proteinuria is a marker associated with delaying disease progression to kidney failure.
The results “exceeded our already high expectations,” Apellis’ chief development officer Jeffrey Eisele, Ph.D., said in a press release. “Pegcetacoplan is the first investigational therapy to show such a strong reduction in proteinuria in C3G and IC-MPGN with supportive data across multiple measures of disease activity.”
The companies aim to build on the drug’s existing PNH label and will “work quickly” to bring the treatment to the new patient population, Eisele added. Apellis will handle an FDA filing in early 2025, while Sobi will submit an application to the European Medicines Agency next year.
With evidence of clinical benefit in two diseases that have no approved treatments, Empaveli now stands to capture a key new market and buoy the drugmaker amid its Syfovre struggles. Also competing in the disease space is Novartis’ Fabhalta, which is approved for PNH.
Apellis’ standout results could apply some pressure on Novartis. In a recent phase 3 C3G study, Fabhalta delivered a tamer 35.1% relative proteinuria reduction versus placebo after six months.
Empaveli’s “enormous efficacy” in the study gave analysts at Evercore ISI reason to designate the medicine with a majority future market share, making the rare kidney disease space a “blockbuster opportunity." In a note to clients, the Evercore ISI team praised the “better than expected” results, especially considering Empaveli’s lack of safety issues compared to those that have hampered Syfovre.
Syfovre is an ophthalmological formulation of pegcetacoplan that hit the market last year. Since then, reports of severe side effects derailed what was at first a flying start. Europe’s Committee for Medicinal Products for Human Use recently issued its second rejection of the GA med.
As for another side of the companies' pursuits with pegcetacoplan, the latest kidney results bring new optimism after Apellis and Sobi scrapped development of the med in amyotrophic lateral sclerosis in the wake of a midstage trial fail. The partners are still evaluating the drug’s use in other rare diseases.