Novartis' Fabhalta Gains Approval for Rare Kidney Disease Therapy

Novartis has achieved a significant milestone by securing a third approval from the U.S. Food and Drug Administration (FDA) for its drug Fabhalta. This newly granted approval is the first for Fabhalta as a treatment for C3 glomerulopathy (C3G), aiming to reduce proteinuria in patients. C3G is an uncommon kidney disorder characterized by the deposition of protein fragments in the glomeruli, potentially leading to end-stage kidney disease within two decades of diagnosis. The average age of individuals diagnosed with this condition is 23, as reported by Novartis.

The recent FDA approval was largely anticipated following successful outcomes from Novartis' Phase III APPEAR-C3G study. The trial demonstrated a reduction in proteinuria from baseline at six months when compared to a placebo. William Blair analysts highlighted this achievement in an investor note released on the day of the announcement.

Previously, in December 2023, Fabhalta received its initial FDA approval for the treatment of paroxysmal nocturnal hemoglobinuria, a rare blood disorder. Subsequent to this, the company secured an accelerated approval in 2024 for Fabhalta as a treatment for primary immunoglobulin A nephropathy, another kidney disease characterized by protein deposits.

The APPEAR-C3G study was a six-month double-blind trial that evaluated a twice-daily oral formulation of Fabhalta. This phase was followed by a six-month open label period during which all participants received the small molecule treatment, including those initially in the placebo group. The results indicated a noticeable reduction in proteinuria, detectable as early as 14 days post-treatment, with sustained effects observed for up to a year while on the medication.

Novartis reported no novel safety concerns during the study. Common side effects included symptoms such as the common cold and viral infections. However, Fabhalta has the potential to cause severe infections like pneumonia and meningitis, linked to encapsulated bacteria such as Streptococcus pneumoniae and Neisseria meningitidis. Therefore, Novartis emphasized that Fabhalta will be dispensed only through a Risk Evaluation and Mitigation Strategy (REMS), which mandates specific vaccinations for patients.

In a statement, Carla Nester, co-investigator of the APPEAR-C3G trial, underscored the significance of this approval for the C3G community. She described it as a historic moment, noting that Fabhalta is now believed to address the underlying cause of the disease, offering the potential to establish a new standard of care for affected patients.

This approval is one of multiple achievements for Novartis this week. Earlier, at the Muscular Dystrophy Association’s Clinical & Scientific Conference, the company presented Phase III data showcasing its spinal muscular atrophy gene therapy, Zolgensma. Originally approved in 2019 as an intravenous treatment for children under two years of age, the data indicated that an intrathecal (IT) formulation of Zolgensma could be effective for older patients with spinal muscular atrophy (SMA). Novartis intends to pursue approval for the IT formulation within the first half of the year, signaling further advancements in their treatment offerings.