IgA nephropathy, the most common primary glomerulonephritis worldwide, has undergone a remarkable transformation in its treatment landscape. Once managed solely with supportive care and immunosuppression of uncertain benefit, the IgA nephropathy drug pipeline now features more than 30 candidates across multiple mechanisms of action, with six therapies already approved in the United States alone. As 2026 unfolds, the convergence of complement inhibitors, APRIL and BAFF pathway blockers, and endothelin receptor antagonists is reshaping how nephrologists approach this progressive kidney disease, and raising urgent questions about sequencing, combination strategies, and long-term outcomes.
An estimated 130,000 to 160,000 people in the United States live with IgA nephropathy, and the condition affects populations across Europe and Asia at comparable or higher rates. The UK National Registry of Rare Kidney Diseases has identified IgA nephropathy as the most frequently biopsied glomerular disease in British centres. Between 20 and 40 per cent of patients progress to end-stage kidney disease within 20 years of diagnosis, a trajectory that makes effective early intervention critical.
The First Wave: Tarpeyo and Filspari
The modern IgA nephropathy drug pipeline began to take shape in December 2021 when the US Food and Drug Administration granted accelerated approval to Tarpeyo (budesonide delayed-release capsules), developed by Calliditas Therapeutics. Tarpeyo became the first therapy specifically approved for IgA nephropathy, targeting the gut-associated lymphoid tissue where aberrant IgA1 production is believed to originate. Full FDA approval followed in December 2023 after confirmatory NefIgArd trial data demonstrated a statistically significant slowing of kidney function decline over two years.
Travere Therapeutics’ Filspari (sparsentan) took a different approach as a dual endothelin type A and angiotensin II receptor antagonist. Initially granted accelerated approval in February 2023, Filspari received full FDA approval in September 2024 based on the PROTECT trial, which showed a 49.8 per cent mean reduction in proteinuria from baseline at 36 weeks and, in the FDA-approved label analysis, a treatment effect of 1.2 mL/min/1.73 m squared per year on eGFR slope at 110 weeks (p=0.0168).
Novartis Secures Two Distinct Approvals
Novartis has positioned itself as a leading force in the IgA nephropathy drug pipeline by securing approvals for two mechanistically distinct therapies. Vanrafia (atrasentan), a selective endothelin A receptor antagonist acquired through the Chinook Therapeutics purchase, received accelerated FDA approval in 2025 for reducing proteinuria in adults with primary IgA nephropathy. Data from the Phase III ALIGN trial, published in The Lancet in June 2026, demonstrated a 34 per cent slower rate of kidney function decline compared to placebo over 2.5 years, with an annualised eGFR slope of negative 2.7 versus negative 4.1 mL/min/1.73 m squared per year.
Dr Richard Lafayette, a nephrologist at Stanford University and ALIGN investigator, stated that these results
“provide robust evidence of clinically meaningful slowing of kidney function decline over more than two years of treatment.”
The company’s second approved agent, Fabhalta (iptacopan), became the first complement inhibitor approved for IgA nephropathy after receiving accelerated approval for proteinuria reduction in August 2024. The APPLAUSE-IgAN trial, published in the New England Journal of Medicine in March 2026, showed that iptacopan slowed kidney function decline by 49.3 per cent compared to placebo over 24 months. Patients receiving the oral Factor B inhibitor had a 43 per cent lower likelihood of progression to kidney failure events. On the strength of those confirmatory results, the FDA converted Fabhalta’s accelerated approval to full traditional approval in July 2026, making it the first complement inhibitor to demonstrate durable preservation of kidney function in IgA nephropathy. Ruchira Glaser, Global Head of Cardiovascular, Renal and Metabolic Development at Novartis, noted that the
“two-year results demonstrate Fabhalta consistently and meaningfully slows kidney decline in high-risk IgAN patients.”
APRIL Pathway Inhibitors Enter the Arena
The recognition that galactose-deficient IgA1 plays a central role in disease pathogenesis has driven significant investment in therapies targeting the APRIL and BAFF signalling pathways. Otsuka’s Voyxact (sibeprenlimab), a monoclonal antibody targeting APRIL, received accelerated FDA approval in November 2025 based on the VISIONARY Phase 3 trial. That study demonstrated a 50 per cent reduction in proteinuria at nine months compared with just two per cent for placebo, a placebo-adjusted treatment effect of 51 per cent.
The most recent addition to the approved treatment roster came on 7 July 2026 when the FDA approved Vera Therapeutics’ Trutakna (atacicept), a first-in-class dual BAFF and APRIL inhibitor, for adults with IgA nephropathy. The ORIGIN 3 Phase 3 trial enrolled 431 patients and demonstrated a 46 per cent proteinuria reduction from baseline at 36 weeks, with a 42 per cent reduction relative to placebo. Trutakna is administered as a weekly subcutaneous injection and carries accelerated approval, with confirmatory eGFR data expected later in 2026.
The Late-Stage Pipeline: Povetacicept and Beyond
Among the most closely watched candidates still in the IgA nephropathy drug pipeline is Vertex Pharmaceuticals’ povetacicept, another dual BAFF and APRIL inhibitor. The RAINIER Phase 3 trial delivered positive interim results at week 36, showing a 52 per cent reduction in proteinuria from baseline and a 49.8 per cent advantage over placebo. Hematuria resolution was achieved in 85.1 per cent of treated patients compared with 23.4 per cent in the placebo group. Notably, 67.7 per cent of patients were receiving SGLT2 inhibitors, the highest proportion of any recent IgA nephropathy trial, suggesting benefit even on top of optimised background therapy. Reshma Kewalramani, Chief Executive Officer of Vertex, described the results as showing
“rapid, deep and sustained response” with “consistency of benefit across all subgroups.”
The FDA accepted Vertex’s Biologics License Application for povetacicept in June 2026, with a decision expected by 30 November 2026. If approved, it would become the seventh IgA nephropathy therapy to reach the US market within five years.
Beyond povetacicept, the broader pipeline spans diverse mechanisms. Novartis is advancing zigakibart, an anti-APRIL monoclonal antibody, through Phase 3 trials. Keymed Biosciences is testing CM313, a CD38 antagonist, in Phase 2. Haisco Pharmaceutical has HSK39297, a complement Factor B inhibitor, in Phase 3. Biohaven’s BHV-1400, a novel galactose-deficient IgA1 degrader, is in early-stage development and represents a mechanistically distinct approach that could target the pathogenic antibody itself.
According to a June 2026 analysis by DelveInsight, more than 25 companies are now actively developing therapies for IgA nephropathy, with approximately 12 candidates in late-stage clinical development.
Competitive Dynamics and Market Outlook
The rapid expansion of approved therapies has created an intensely competitive market. Vera Therapeutics estimates the US IgA nephropathy market at approximately $20 billion based on current pricing benchmarks, though independent estimates vary, a figure that reflects both the chronic nature of the disease and the premium pricing commanded by these targeted therapies.
Differentiation among the growing roster of approved agents is emerging as a central challenge. Dr Krzysztof Kiryluk, a nephrologist at Columbia University, has observed that “if efficacy and eGFR outcomes are equivalent, differentiation will hinge on safety, dosing convenience, monitoring requirements and insurance coverage.” Current options range from daily oral tablets to monthly subcutaneous injections, and their mechanisms span complement inhibition, endothelin receptor blockade, targeted corticosteroid release, and APRIL/BAFF pathway modulation.
The question of combination therapy looms large over the field. With multiple approved agents targeting different nodes of IgA nephropathy pathophysiology, clinicians and researchers are increasingly considering whether sequential or combination strategies could deliver additive benefit. The KDIGO 2025 guidelines acknowledged the rapidly evolving landscape but stopped short of recommending specific combination approaches, citing the absence of head-to-head and combination trial data.
Remaining Challenges
Despite the remarkable progress in the IgA nephropathy drug pipeline, important questions remain unanswered. Three of the six approved therapies, Tarpeyo, Filspari and Fabhalta, have now secured full FDA approval on the basis of confirmatory kidney function data, while the remaining three hold accelerated approvals based on proteinuria reduction as a surrogate endpoint, meaning confirmatory trials demonstrating durable preservation of kidney function are still underway. Whether early and aggressive intervention can fundamentally alter the long-term trajectory of the disease, rather than simply delaying progression, remains to be established.
Access and equity present additional challenges. The global burden of IgA nephropathy is particularly high in East Asian populations, where incidence rates are two to three times higher than in European cohorts. Ensuring that therapeutic advances developed predominantly in Western clinical trial populations are accessible and applicable to patients in high-burden regions will require sustained effort from regulators, manufacturers, and health systems alike.
For patients and clinicians, the transformation of IgA nephropathy from a condition with no approved treatments to one with six approved therapies and a robust late-stage pipeline represents a watershed moment in nephrology. The coming months will determine whether the current wave of approvals translates into meaningful improvements in long-term kidney survival.
