POSITIVE RESULTS

Health Canada approves Novartis's Vanrafia for IgA nephropathy proteinuria

The approval rests on the same Week 36 interim UPCR reduction that already won US accelerated approval, with the ALIGN trial's eGFR-based final analysis still to come.

Health Canada approved VANRAFIA (atrasentan tablets) to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression, based on the Phase III ALIGN interim analysis.

By AppliedXLJuly 13, 2026Trial NCT04573478

Executive Summary

Health Canada cleared atrasentan for proteinuria reduction in IgA nephropathy, extending a regulatory pathway already opened in the United States on the same interim trial data.
The result behind both approvals is a statistically significant reduction in proteinuria at Week 36, a surrogate marker regulators have accepted to support accelerated approvals in this disease.
The trial's own registrational endpoint, a kidney-function measure taken years later in the study, has not yet read out, leaving the durability question for the final analysis to answer.
No other active trial in this indication targets the same receptor, leaving atrasentan the only program built on this specific mechanism to have reached regulatory decisions in this disease so far.

The decision

Novartis Pharmaceuticals Canada Inc. announced on July 13, 2026 that Health Canada granted approval for VANRAFIA (atrasentan tablets), an oral, selective Endothelin A (ETA) receptor antagonist, for proteinuria reduction in adults with primary IgA nephropathy (IgAN) at risk of rapid disease progression, generally defined as a urine protein-to-creatinine ratio (UPCR) of at least 1.5 g/g. The authorization rests on a prespecified interim analysis at Week 36 of the Phase III ALIGN study (NCT04573478), a randomized, double-blind, placebo-controlled trial in 404 adults with biopsy-proven primary IgAN on a stable, maximally tolerated dose of a renin-angiotensin system inhibitor. Novartis+1

The evidence behind it

The interim data were first disclosed in May 2024: atrasentan produced a 36.1% reduction in 24-hour UPCR versus placebo at Week 36, with a p-value below 0.0001, presented in a late-breaking session at the European Renal Association Congress. That same result, described in the Health Canada release only as a statistically significant reduction in UPCR at Week 36, is the evidentiary basis for the Canadian approval. "ETA receptor activation causes proteinuria, which is usually one of the first clinical signs of IgAN," said Hiddo Heerspink, professor of clinical trials and personalized medicine at the University Medical Center Groningen and the ALIGN steering committee chair, in the 2024 disclosure. Novartis+1

What the trial still owes

ALIGN continues in blinded fashion toward its final analysis, which will report the key secondary endpoint: change from baseline in estimated glomerular filtration rate (eGFR), a kidney-function measure, at Week 136. That endpoint, not the interim proteinuria signal, is what determines whether the surrogate benefit translates into slower disease progression. The trial's primary completion date has moved twice since 2024, from September 2023 out to December 2026 and then to April 2028. Enrollment has been complete at 404 patients, actual, since August 2024, and the trial has carried an Active, not recruiting status since May 2023. Novartis+1

Regulatory sequence

The Canadian clearance follows the FDA's accelerated approval of Vanrafia in the same population on April 3, 2025, also built on the ALIGN interim analysis. Both decisions rely on proteinuria reduction as a surrogate marker, an endpoint regulators have accepted to support accelerated approvals in IgAN. The sequence shows the interim result carrying regulatory weight across multiple markets before the trial's own final analysis has reported. Novartis+1

Competitive position

No other active trial studying the ET_A receptor in IgA nephropathy exists, based on the current trial landscape, leaving atrasentan without a direct target-sharing comparator in this indication. The nearest same-modality precedent, Novartis's iptacopan, targets complement factor B rather than the endothelin pathway, and Takeda's mezagitamab and Novartis's zigakibart pursue CD38 and APRIL, respectively, all different mechanisms competing for the same proteinuria-reduction endpoint in Phase 3 IgAN trials.

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.