An ultra-rare kidney disease that can become life-threatening now has its first FDA-approved therapy. The affirmative regulatory decision is the third for Novartis’s Fabhalta, building up the drug’s pipeline-in-a-product potential. But competition looms from a rival drug taking a similar approach.
The March 20 approval of Fabhalta covers the treatment of adults with C3 glomerulopathy (C3G), a disease affecting glomeruli, tiny blood vessels in the kidney responsible for filtering waste from the blood. C3G can progress to kidney failure. With no therapies specifically approved for this disease until now, standard treatment included supportive care, broad immunosuppression, and symptom management.
C3G stems from excessive activity in a pathway of the complement system, a part of the immune system. Overactivation of this pathway leads to deposits of the complement protein C3 in glomeruli, triggering inflammation and kidney damage. Fabhalta is an oral small molecule designed to bind to and block an alternative complement protein, Factor B. The twice-daily pill was first approved in 2023 as a treatment for paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disease. Last year, the drug expanded its approval to include the rare autoimmune kidney disease IgA nephropathy.
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Novartis’s Fabhalta submission in C3G was based on a placebo-controlled Phase 3 test that evaluated the study drug alongside supportive care. Compared to a placebo, treatment with the twice-daily drug for six months led to a 35% reduction in proteinuria, levels of urine proteins indicative of kidney disease. This reduction was observed as early as 14 days after starting treatment; the therapeutic effect was sustained at 12 months.
The most common adverse reactions reported in the pivotal study were nasopharyngitis and viral infections. The drug’s label carries a black box warning for the risk that patients may develop serious infections from encapsulated bacteria, a warning that came with the drug’s initial approval in PNH. Fabhalta is available only through a restricted program that manages these risks. Patients must receive vaccinations for encapsulated bacteria at least two weeks prior to the first Fabhalta dose and clinicians should monitor patients for serious signs of infection.
Novartis has projected Fabhalta could reach $3 billion in peak sales across several indications. It still has a way to go. The drug accounted for $129 million in revenue in 2024, according to the company’s annual report. To expand use of the drug and maximize its revenue potential, Novartis is running several concurrent clinical studies in other rare kidney diseases, such as immune complex membranoproliferative glomerulonephritis (IC-MPGN).
In its approved use in PNH, Fabhalta already competes with Empaveli, a twice-weekly infusion from Apellis Pharmaceuticals that blocks the complement system protein C3. The two drugs could also become competitors in C3G and IC-MPGN. Apellis has submitted an application to the FDA seeking to expand its drug’s approval to both indications. The filing was based on the results of a Phase 3 study showing the drug led to a statistically significant 68% reduction in proteinuria measured at six months. The drug is being developed under a partnership with Sobi; the Swedish company has exclusive rights to commercialize systemic Empaveli outside of the U.S.
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In a note sent to investors Friday, William Blair analyst Lachlan Hanbury-Brown said Fabhalta’s new approval in C3G bodes well for Empaveli, whose data show it to be best-in-class for both C3G and IC-MPGN. Clinicians have told the firm that their selection of a treatment for these rare kidney diseases will be driven by efficacy rather than potential patient preference for an oral therapy. The efficacy measure clearly favors Empaveli.
“With roughly 5,000 patients in the U.S., no approved therapies to date (and still none for IC-MPGN or adolescents with either disease), and a clearly differentiated product profile, we see this as a significant market opportunity for Apellis,” Hanbury-Brown wrote.
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