Novartis' Fabhalta secures FDA approval for IgA nephropathy

Novartis recently announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval to Fabhalta (iptacopan) for reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) who are at high risk of disease progression. This marks Fabhalta’s second indication in the U.S., following its prior approval in December for paroxysmal nocturnal haemoglobinuria (PNH).

The approval positions Fabhalta as a significant competitor in the IgAN treatment landscape, challenging existing medications such as Calliditas' Tarpeyo (budesonide) and Travere Therapeutics' Filspari (sparsentan), which gained FDA approval in 2021 and 2023, respectively. Victor Bultó, president of Novartis US, hailed the approval as a critical milestone in advancing care for rare renal diseases, emphasizing the urgency of providing new treatment options to individuals in need.

The FDA's decision was supported by interim results from the ongoing Phase III APPLAUSE-IgAN trial. In this study, 470 adults with primary IgAN who were already stabilized on renin-angiotensin system (RAS) inhibitors, with or without sodium-glucose co-transporter-2 (SGLT2) inhibitors, were randomized to receive either Fabhalta or a placebo, both in combination with supportive care. The primary endpoint was the percentage reduction in proteinuria at nine months from baseline, measured using the urine protein-to-creatinine ratio (UPCR).

Findings revealed a 44% reduction in proteinuria in the Fabhalta group compared to a 9% reduction in the placebo group after nine months. This translates to a clinically significant 38% reduction for Fabhalta versus placebo. Moreover, the benefits were consistent across various subgroups, including different ages, sexes, races, baseline disease characteristics, and SGLT2 inhibitor use.

Notably, full approval of Fabhalta will depend on demonstrating a clinical benefit in slowing disease progression, measured by the decline in glomerular filtration rate (eGFR) over a 24-month period. The eGFR data is expected to be available upon the study's completion next year. As with its earlier indication, Fabhalta will only be accessible through a Risk Evaluation and Mitigation Strategy (REMS) that necessitates vaccinations for encapsulated bacteria.

Beyond Fabhalta, Novartis is advancing its IgAN treatment pipeline with two other therapies: atrasentan and zigakibart. Atrasentan is an oral endothelin A receptor antagonist currently under FDA review following the successful Phase III ALIGN trial. Zigakibart, a subcutaneous anti-APRIL monoclonal antibody, is in late-stage development.

Additionally, Fabhalta is being investigated for its efficacy in treating C3 glomerulopathy. In this context, the drug met its primary objective in the Phase III APPEAR-C3G trial.

These developments underscore Novartis' commitment to addressing unmet needs in rare renal diseases by expanding therapeutic options and improving patient outcomes. The continued progress in clinical trials and subsequent FDA reviews will be crucial in determining the long-term impact of these treatments on disease management and patient quality of life.