What is IgA Nephropathy?
IgAN results from the buildup of IgA antibodies in the kidneys, which can trigger inflammation and progressive damage. Over time, this leads to proteinuria, hematuria, decreased renal function, and in up to 40% of cases, end-stage renal disease (ESRD) within 20 years.
While supportive therapies like RAAS inhibitors and steroids remain foundational, the emergence of complement inhibitors, immunomodulators, and kidney-targeted biologics is reshaping the treatment landscape.
The Competitive Landscape: Key Players and Pipeline Highlights
1. Approved Therapies and Front-Runners
- Tarpeyo® (budesonide delayed-release) – Calliditas Therapeutics
Approved in 2021 under accelerated approval, Tarpeyo is a targeted corticosteroid designed to act on Peyer’s patches in the ileum, reducing IgA production at its mucosal origin. It was the first FDA-approved treatment specifically for IgAN. - Filspari™ (sparsentan) – Travere Therapeutics
This dual-acting angiotensin and endothelin receptor antagonist was approved in 2023 under accelerated approval for IgAN. The PROTECT study it demonstrated significant reductions in proteinuria and is expected to help slow disease progression pending confirmatory data. - Fabhalta® (iptacopan) – Novartis
As of August 2024, Fabhalta received FDA accelerated approval as the first and only complement inhibitor for IgAN. This oral factor B inhibitor acts on the alternative complement pathway. - Vanrafia® (atrasentan) – Novartis
Approved in April 2025 under accelerated approval, Vanrafia is a once-daily, non-steroidal, oral selective endothelin A (ETA) receptor antagonist. It is indicated to reduce proteinuria in adults with primary IgAN at risk of rapid disease progression.
| Drug | Company | Mechanism | Approval Year | Key Differentiator |
| Tarpeyo® | Calliditas Therapeutics | Targeted-release budesonide (corticosteroid) | 2021 | First FDA-approved drug for IgAN |
| Filspari™ | Travere Therapeutics | DEARA – Dual endothelin/angiotensin blocker | 2023 | Strong proteinuria reduction, oral therapy |
| Fabhalta® | Novartis | Oral factor B inhibitor (complement pathway) | 2024 | First complement inhibitor approved for IgAN |
| Vanrafia® | Novartis | Selective endothelin A receptor antagonist | 2025 | Once-daily oral ERA with no REMS requirement |
2. Mid-to-Late-Stage Pipeline Candidates
- Zigakibart – Novartis
A monoclonal antibody against APRIL, aiming to directly reduce the production of pathogenic IgA1. Currently in Phase III trials, with a unique mechanism targeting upstream immune triggers. - Povetacicept– Vertex Pharmaceuticals
It is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in the pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation, and/or survival of B cells, T cells, and innate immune cells.
| Company | Drug | Stage | Mechanism | Modality | RoA |
| Novartis | Zigakibart | Phase III | Anti-APRIL monoclonal antibody | Monoclonal Antibody | SC |
| Vertex | Povetacicept | Phase III | Dual BAFF/APRIL inhibition | Fusion Protein | SC |
| Roche | Sefaxersen | Phase III | Complement factor B inhibitor | Antisense oligonucleotide | SC |
| Otsuka | Sibeprenlimab | Phase III | Anti-APRIL monoclonal antibody | Monoclonal Antibody | SC |
| AstraZeneca | Ravulizumab (Ultomiris I CAN) | Phase III | Anti-complement C5 mAb | Monoclonal Antibody | IV |
| Arrowhead Pharmaceuticals | ARO-CFB | Phase I/II | Complement factor B inhibitor | Antisense oligonucleotide | SC |
| Takeda | Mezagitamab | Phase I | Anti-CD38 mAb | Monoclonal Antibody | SC |
What’s Next?
With Fabhalta, Tarpeyo, Vanrafia, and Filspari now approved, the IgAN treatment paradigm is shifting from broad immunosuppression to targeted, pathway-specific intervention. Complement inhibitors are clearly leading the charge, but immune signaling modulators and precision therapies are not far behind.
The next 12–24 months will be critical as more Phase III data rolls in and the market dynamics evolve. Expect to see head-to-head studies, label expansions, and payer shifts as these agents move toward broader adoption.
Final Thoughts
The IgA nephropathy market is rapidly evolving, with four FDA-approved therapies now offering targeted options for patients. As competition intensifies, the focus is turning to long-term kidney protection, ease of use, and safety. With promising drugs still in late-stage development, the field is entering a new era bringing real hope to patients and major opportunities for innovators.
For now, Novartis has taken an early lead with Fabhalta and Vanrafia. But competition remains wide open, and companies with a promising Phase II or III asset is now playing for high stakes in a multi-billion-dollar global market.
