Novartis' Fabhalta Receives FDA Approval for C3G, Faces Potential Competition from Apellis

Novartis has secured a groundbreaking FDA approval for Fabhalta (iptacopan) in the treatment of complement 3 glomerulopathy (C3G), an ultra-rare kidney disease. This approval marks a significant milestone in the nephrology field, as Fabhalta becomes the first therapy endorsed by the FDA for C3G. However, the drug's label reveals potential limitations that may leave room for rival Apellis Pharmaceuticals to make inroads with its competing treatment, Empaveli (pegcetacoplan).

Fabhalta's Approval and Clinical Data

The FDA has cleared Fabhalta to reduce proteinuria in adults with C3G, a condition affecting approximately 1 to 2 people per million worldwide annually. The approval is based on data from the phase 3 Appear-C3G trial, which demonstrated a statistically significant 35% relative reduction in proteinuria from baseline compared to placebo after six months of treatment.

Dr. Carla Nester from the University of Iowa, an investigator in the Appear-C3G study, hailed the approval as "historic for the entire C3G community," noting that Fabhalta is believed to treat the underlying cause of the disease.

Fabhalta, an oral medication that works by inhibiting complement factor B, has shown maintained efficacy at 12 months. Patients who switched from placebo to Fabhalta experienced similar improvements in proteinuria reduction.

Competitive Landscape and Potential Challenges

Despite being first to market, Fabhalta may face stiff competition from Apellis' Empaveli, which is also being developed for C3G. Analysts from Citi and William Blair view Empaveli as potentially superior, citing more impressive efficacy data from its phase 3 Valiant trial, which showed a 68% relative reduction in proteinuria versus placebo after six months.

The FDA label for Fabhalta includes specific language that may allow Apellis to differentiate Empaveli:

1. Fabhalta's approval is limited to adults, while Empaveli's trial included adolescents.
2. The label specifies that Fabhalta's efficacy has not been established in C3G patients following kidney transplant, an area where Empaveli has data.
3. The indication explicitly states Fabhalta is used "to reduce proteinuria," potentially limiting its perceived benefits.

Novartis' Strategy and Market Position

Victor Bulto, president of Novartis U.S., emphasized the synergy between Fabhalta's launch and the company's existing presence among nephrologists. Fabhalta is part of Novartis' broader kidney disease portfolio, which includes two other medications targeting different mechanisms of action.

Bulto argued that C3G's heterogeneity makes cross-trial comparisons difficult and stressed the importance of stabilizing estimated glomerular filtration rate (eGFR) in patients. However, Fabhalta's label notes no significant difference between treatment arms in the proportion of patients with stable or improved eGFR at 6 months.

As the pharmaceutical landscape for C3G treatment evolves, the coming months will likely reveal whether Novartis can leverage its first-mover advantage and broader kidney disease portfolio, or if Apellis can capitalize on potentially stronger efficacy data to challenge Fabhalta's position in this rare disease market.