Novartis clinches FDA approval for second IgAN drug

SWITZERLAND – Novartis has recently secured accelerated approval from the U.S. Food and Drug Administration (FDA) for Vanrafia (atrasentan), an innovative therapy aimed at transforming the treatment of IgA nephropathy (IgAN).

This approval marks a significant milestone as Vanrafia becomes the first selective endothelin A receptor antagonist (ERA) cleared in the U.S. for treating this rare kidney disease.

IgA nephropathy is characterized by the accumulation of antibodies in the kidneys, leading to inflammation and scarring.

Despite the use of standard care, up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years after diagnosis.

With approximately 25 new cases per million people diagnosed each year—mostly affecting young adults—there is a pressing need for innovative therapies that can alter the disease trajectory.

Vanrafia addresses this unmet need by reducing proteinuria, a key biomarker for kidney damage, in adult IgAN patients who are at risk of disease progression.

The accelerated approval of Vanrafia is based on promising 36-week proteinuria data from the pivotal ALIGN study.

The trial demonstrated a 38.1% reduction in proteinuria in patients treated with the ERA, compared to a minimal 3.1% reduction in those receiving a placebo.

While these results underscore Vanrafia’s potential as a “foundational” treatment, full regulatory approval will hinge on further data from the ALIGN study, specifically on estimated glomerular filtration rate (eGFR), a more robust marker of kidney function, expected to be released next year.

Designed as an oral, once-daily therapy, Vanrafia can be seamlessly integrated with existing treatments, such as renin-angiotensin system (RAS) inhibitors and SGLT-acting drugs.

Novartis envisions Vanrafia as a versatile option for the over 500,000 patients affected by IgAN worldwide, including around 45,000 in the United States.

In contrast, the company estimates that its complement inhibitor Fabhalta (iptacopan), which is already available in the U.S. for IgAN, may only be suitable for 15% to 30% of patients.

This approval further strengthens Novartis’s commitment to transforming the IgAN treatment landscape.

Alongside Vanrafia, the company is also advancing its pipeline with a third investigational product, an anti-APRIL antibody called zigakibart, which is currently in phase 3 clinical trials and targeted for launch from 2027 if approved.

The evolving market for IgAN therapies is witnessing intense competition. In 2021, Calliditas Therapeutics’ corticosteroid-based Tarpeyo became the first FDA-approved treatment for IgAN.

In 2023, Travere Therapeutics joined the market with Filspari (sparsentan), although its use is governed by a strict risk evaluation and mitigation strategy (REMS) to manage potential side effects like liver toxicity and birth defects.

Other players, such as Otsuka and Biogen, are also making significant strides with their own innovative candidates in this space.