Atrasentan Shows Long-Term Kidney Benefits in IgA Nephropathy Trials
Final phase 3 trial results show atrasentan (Vanrafia®) provides significant long-term kidney function benefits in IgA nephropathy patients, with a 2.59 mL/min/1.73m² eGFR improvement versus placebo. Earlier phase 2 data demonstrated the drug reduces proteinuria by 30.7% when added to standard background therapy. The drug's manufacturer plans to seek traditional FDA approval in 2026 based on these findings.
The selective endothelin-A receptor antagonist atrasentan has demonstrated significant long-term kidney function benefits in patients with IgA nephropathy, according to final results from a phase 3 trial. The drug, marketed as Vanrafia®, showed a difference of 2.59 mL/min/1.73m² in estimated glomerular filtration rate (eGFR) change from baseline compared with placebo at week 132, with the benefit persisting through week 136. These findings build on earlier phase 2 results showing the drug's ability to reduce proteinuria when added to standard background therapy.
In the phase 3 ALIGN trial, treatment with atrasentan showed a statistically significant difference of 2.59 mL/min/1.73m² (P =.039) in eGFR change from baseline compared with placebo at week 132, which marks the end of the treatment period. The benefit remained evident at week 136, showing a difference of 2.39 mL/min/1.73m² versus placebo (P =.057). Clinically meaningful effects were also observed in prespecified exploratory groups of patients receiving sodium-glucose co-transporter-2 inhibitors.
Earlier phase 2 findings from the ASSIST trial demonstrated that atrasentan additionally reduces proteinuria when combined with maximally tolerated renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 inhibitors. In that randomized, double-blind, placebo-controlled crossover trial involving 54 adults with IgA nephropathy, atrasentan reduced urinary protein-to-creatinine ratio by a geometric mean of -30.7% compared with -7.2% with placebo over 12 weeks. The difference in UPCR between treatment and placebo conditions was -25.3%.
At 24 weeks, following a washout period, atrasentan use led to a -27.0% reduction in UPCR compared with -0.9% with placebo. This antiproteinuric effect was consistent across treatment sequences and supported by sensitivity analyses, with no evidence of a carryover effect. Notably, UPCR returned to baseline following washout, indicating a reversible pharmacodynamic effect.
Kidney function remained stable throughout the phase 2 study, with eGFR change at week 24 showing 0.3 mL/min/1.73 m², suggesting no short-term adverse impact of treatment on filtration. Blood pressure, body weight, B-type natriuretic peptide, and hemoglobin values changed minimally, further supporting hemodynamic stability.
The safety profile of atrasentan has been consistent across studies. The most common adverse reactions reported in clinical trials were peripheral edema and anemia. In the phase 2 trial, treatment-emergent adverse events were comparable and predominantly mild or moderate during active treatment and placebo conditions. Fluid retention events occurred more frequently with atrasentan but were generally manageable and did not lead to hospitalization or treatment discontinuation.
The phase 3 results support the drug's potential as a foundational therapy to slow kidney function decline in IgA nephropathy patients. The company intends to seek traditional approval for Vanrafia in 2026 based on the final data from the ALIGN study. Atrasentan received accelerated approval from the Food and Drug Administration in April 2025 based on interim results from the ALIGN trial demonstrating reduction in proteinuria with atrasentan versus placebo at week 36.