Domestic approval of 'Vanrafia' is imminent…new IgAN drug entries expected

Commercialization of new follow-on drugs is underway following Nefecon

Has been confirmed to reduce proteinuria and slow declines in kidney function

Novartis’ new IgA nephropathy (IgAN) drug, Vanrafia, is nearing regulatory approval in South Korea, signaling anticipated shifts in the treatment landscape.

As regulatory approval for Vanrafia, which targets the disease's pathogenic and progression pathways, nears, the reimbursement status of the previously approved Nefecon is expected to become a critical factor shaping prescribing competition.

Novartis’ Vanrafia

According to industry sources on the 7th, Novartis Korea is currently pursuing domestic approval for Vanrafia (atrasentan). The company anticipates an approval decision as early as this month.

Vanrafia selectively antagonizes endothelin A (ETA) receptors involved in renal damage, aiming to reduce proteinuria and slow declines in kidney function.

Vanrafia is formulated for oral administration at 0.75 mg once daily and can be taken with or without food.

Last year, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Vanrafia based on clinical evidence of reduced proteinuria in patients with primary IgAN.

In the Phase 3 ALIGN trial, which was the basis for approval, Vanrafia demonstrated significant proteinuria reduction, and subsequent long-term follow-up evaluated its nephroprotective effects.

In the final analysis, Vanrafia demonstrated a 38.3% reduction in proteinuria compared with placebo at 9 months. In an analysis tracking patients over approximately 2.5 years, it reduced the rate of kidney function decline by approximately 34% versus placebo.

Nefecon enters the Korean market first… Reimbursement status as the key variable

After Vanrafia receives domestic approval, a new competitive landscape is expected to emerge in the IgAN therapeutic market alongside the previously approved Nefecon.

Everest Medicines Korea’s Nefecon (micronized budesonide) secured approval from the Ministry of Food and Drug Safety (MFDS) in November 2024 for adult patients with primary IgAN who have a 24-hour urine protein excretion of ≥1 g/day or a urine protein-to-creatinine ratio (UPCR) of ≥0.8 g/g.

Nefecon is a targeted-release formulation designed to deliver budesonide to specific regions of the distal ileum. Its mechanism of action differs from Vanrafia, which targets ETA receptors, by modulating the mucosal immune response implicated in IgAN pathogenesis.

Dosing regimens also differ. Nefecon is indicated for 16 mg once-daily for 9 months, followed by a dosage taper before discontinuation.

Because no direct head-to-head clinical trials exist between Nefecon and Vanrafia, a simple comparison of comparative efficacy remains challenging. However, because they target distinct pathophysiological pathways, clinical options can broaden based on individual patient characteristics.

Reimbursement will determine actual market uptake.

Everest Medicines Korea’s new IgA nephropathy (IgAN) drug, Nefecon

Everest Medicines suffered a setback last year in its initial bid for Nefecon’s reimbursement. In May of this year, the company submitted supplemental data to reapply, which is currently under review by the Health Insurance Review and Assessment Service (HIRA).

Once Vanrafia is approved, the insurance coverage status and reimbursement criteria for each agent will directly govern real-world prescribing patterns.

IgAN is a chronic, progressive disease requiring long-term clinical management. Even if therapeutics are approved, high out-of-pocket costs inevitably pose significant barriers to real-world patient access.

The non-reimbursed price of Nefecon disclosed across major medical institutions stands at approximately KRW 50,000 to 60,000 per capsule. Converted to monthly treatment costs, this amounts to around KRW 7 million.

The reimbursement outcome for Nefecon could serve as an initial benchmark for defining the future reimbursement scope of novel IgAN therapies. However, given the differing mechanisms of action and clinical evidence profiles between the two drugs, their reimbursement criteria and pharmaco-economic evaluation frameworks may diverge.

Successive entry of novel therapeutics… Treatment options diversify

IgA nephropathy is characterized by the glomerular deposition of immunoglobulin A (IgA), which triggers progressive inflammation and renal damage. As renal function continually declines, a subset of patients progresses to end-stage renal disease (ESRD).

Previously, standard of care centered on supportive therapy utilizing renin-angiotensin system (RAS) inhibitors to manage proteinuria and blood pressure. Recently, the successive emergence of therapies like Nefecon and Vanrafia, which directly target specific pathways involved in disease onset and progression, is transforming the therapeutic paradigm.

Beyond Vanrafia, Novartis also holds Fabhalta (iptacopan), a complement pathway inhibitor, in its IgAN pipeline.

Fabhalta received regular FDA approval in July of this year as a treatment to slow the decline of kidney function in adult patients with primary IgAN. In the Phase 3 APPLAUSE-IgAN trial, Fabhalta demonstrated an approximate 48% reduction in the rate of kidney function decline compared with placebo over two years.

Additionally, novel mechanism-based therapies such as Filspari (sparsentan), a dual endothelin-angiotensin receptor antagonist, have already secured approval and utilization in the United States. Furthermore, with investigational candidates targeting the APRIL signaling pathway entering development, IgAN management is progressively shifting from conventional proteinuria mitigation toward precision targeting of underlying disease progression mechanisms.

In contrast, few novel therapies have entered the domestic market to date. With Nefecon securing the initial approval and Vanrafia now preparing for subsequent market entry, clinically available options remain limited compared with the global market.