Novartis Gains 2.5-Year Phase III eGFR Data Supporting Vanrafia Traditional Approval Bid in IgAN

Novartis's accelerated approval conversion strategy for Vanrafia® (atrasentan) now has confirmatory eGFR data behind it, the kind of long-term functional endpoint that FDA expects to see before granting traditional approval under its evolving post-accelerated approval framework. Final 2.5-year results from the Phase III ALIGN trial (NCT04573478), published in The Lancet and presented at the European Renal Association Congress on June 4, show statistically significant slowing of kidney function decline versus placebo in adults with IgA nephropathy.

The primary confirmatory endpoint, change from baseline in eGFR at end of study in the main cohort, favored Vanrafia, with annualized eGFR slope data expressed in mL/min/1.73 m²/year. Sustained reductions in urine protein-to-creatinine ratio (UPCR) were maintained through Week 132, consistent with the earlier interim proteinuria analysis that underpinned the 2025 accelerated approvals in the U.S. and China. Notably, benefits held across subgroups receiving concomitant SGLT2 inhibitors, a clinically relevant finding given the increasing use of that drug class in CKD management.

The ALIGN trial enrolled 340 patients with biopsy-proven IgAN and baseline total proteinuria ≥1 g/day despite optimized renin-angiotensin system (RAS) inhibitor therapy, randomized to once-daily oral Vanrafia 0.75 mg or placebo for approximately 132 weeks. An additional cohort of 64 patients on background SGLT2 inhibitor therapy was enrolled separately. Safety findings were consistent with prior studies; adverse event rates were similar to placebo with no new signals identified.

For regulatory affairs teams, the dataset represents a direct test case in confirmatory trial design under 21 CFR Part 314 Subpart H and the post-Omnibus Reform Act environment, where FDA has tightened expectations around the timing and rigor of post-accelerated approval verification studies. Novartis has stated it intends to submit for traditional approval in 2026, meaning the regulatory package will be assembled and filed within the current inspection and review cycle.

IgAN affects approximately 25 people per million worldwide annually, with up to 50% of patients with persistent proteinuria progressing to kidney failure within 10 to 20 years of diagnosis. The disease burden, dialysis, transplantation, and the associated quality-of-life deterioration, has historically been managed with supportive RAS inhibition alone, a standard that targeted therapies are now beginning to displace.

The submission timeline Novartis has committed to will serve as a measurable checkpoint for how quickly a confirmatory eGFR dataset can move through the traditional approval conversion process under current FDA review priorities.

Source: Novartis via GlobeNewswire, June 4, 2026. Results presented at the European Renal Association Congress and published in The Lancet.