Sayna Norouzi, MD, is an assistant professor of medicine and clinical nephrologist at Loma Linda University Medical Center

Sayna Norouzi, MD

Rare Disease Day 2026: Kidney Diseases Enter Optimistic Therapeutic Era

On Rare Disease Day 2026, 4 clinicians share their insights and perspectives on the groundbreaking improvements in the rapidly evolving field of rare kidney diseases.

Despite persistent awareness gaps in rare kidney disease care, a wave of FDA approvals and phase 3 trial successes in 

 alongside updated 2025 KDIGO Practice Guidelines, has fueled growing clinician optimism about a rapidly advancing, disease-modifying treatment era.

Rare kidney diseases remain complex and underrecognized, leaving both patients and clinicians with challenges in early diagnosis, risk stratification, and long-term management. Yet recent scientific advances and regulatory approvals are beginning to reshape the therapeutic landscape.

Momentum in rare kidney disease care has accelerated with multiple FDA approvals supported by pivotal clinical trial data. In IgAN, 

demonstrated significant reductions in proteinuria and preservation of kidney function in the NefIgArd trial, while 

, a dual endothelin-angiotensin receptor antagonist, showed positive outcomes in the PROTECT study. The addition of 

, an endothelin A receptor antagonist, further underscores the diversification of therapeutic strategies in IgAN, with the ALIGN Phase III trial demonstrating clinically meaningful reductions in proteinuria, a key surrogate for slowing disease progression. Iptacopan, a factor B inhibitor targeting the alternative complement pathway, reported encouraging efficacy in the APPLAUSE-IgAN trial, highlighting a precision-based approach to treatment.

In C3G, iptacopan also showed promising results in the 

, alongside other complement-targeted therapies such as 

 and danicopan, reflecting growing opportunities for disease modification in a previously limited treatment space.

These advances are complemented by the updated 

, which provide evidence-based recommendations to support clinicians in diagnosis, monitoring, and treatment selection, fostering a more standardized and patient-centered approach.

Together, these therapies, spanning endothelin-angiotensin signaling modulation, complement inhibition, and targeted anti-inflammatory strategies, illustrate a shift toward precision medicine in rare kidney disease. 

6 New Kidney Disease Medications Approved in 2025. National Kidney Foundation. Published January 21, 2026. 

https://www.kidney.org/news-stories/6-new-kidney-disease-medications-approved-2025

Sayna Norouzi, MD, Cheung K, Skolnik E, Peleg Y. 2025 KDIGO Guideline Update for IgAN. Hcplive.com. Published January 14, 2026. Accessed February 28, 2026. https://www.hcplive.com/view/2025-kdigo-guideline-update-for-igan

Perkovic V, Barratt J, Rovin BH, et al; APPLAUSE‑IgAN Investigators. 

Alternative complement pathway inhibition with iptacopan in IgA nephropathy.

 N Engl J Med. 2025;392(6):531‑543. doi:10.1056/NEJMoa2410316. Published online 2024 Oct 25.

Kavanagh D, Bomback AS, Vivarelli M, et al. 

Oral iptacopan therapy in patients with C3 glomerulopathy: a randomized, double‑blind, placebo‑controlled, phase 3 study.

 Lancet. 2025;406(10512):1587‑1598. doi:10.1016/S0140‑6736(25)01148‑1.

Lafayette R, et al; NefIgArd Investigators. 

Efficacy and safety of a targeted‑release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2‑year results from a randomized phase 3 trial.

KDIGO IgAN and IgA Vasculitis Work Group; Rovin BH, Barratt J, Cook HT, et al. 

KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV).

 Kidney Int. 2025;108(4S):S1‑S71. doi:10.1016/j.kint.2025.04.004.

Novartis receives FDA accelerated approval for Fabhalta (iptacopan), the first and only complement inhibitor for reduction of proteinuria in adults with primary IgA nephropathy.

Novartis investigational atrasentan Phase III study demonstrates clinically meaningful proteinuria reduction in patients with IgA nephropathy (ALIGN).

Videos

On Rare Disease Day 2026, clinicians share their perspective on the evolving landscape for IgAN and C3G. 

Factor D Inhibition Lacks Efficacy For IgAN in Phase 2 ALXN2050 Trial, With Sayna Norouzi 

New data from the phase 2 study of ALXN2050 (vemircopan) showed a non-statistically significant urine protein reduction compared to placebo, suggesting factor D inhibition is not an effective therapy for 

Findings from the randomized, placebo-controlled phase 2 trial of ALXN2050, presented by study investigator Sayna Norouzi, MD, an assistant professor of medicine and clinical nephrologist at Loma Linda University Medical Center, at the 

American Society of Nephrology Kidney Week 2025

, showed a clear lack of efficacy and signaled emerging safety concerns in adults with IgAN.¹

With an evolving understanding of the pathogenesis of IgAN, clinical research has investigated the potential of immune and complement-targeted therapies to change the disease course. In line with this, ALXN2050 is an oral small-molecule designed for the selective inhibition of factor D, a serine protease largely produced in adipocytes, and the rate-limiting enzyme in the activation sequence of the alternative pathway.

“Since iptacopan showed significant benefits and aligns with our understanding of IgAN pathophysiology, it made sense to evaluate a factor D inhibitor in IgAN to see whether it could interrupt the disease process at Hit 4,” Norouzi said in an interview with 

. “But early data from this study suggest we should not continue pursuing a factor D inhibitor in IgAN.”

In the 26-week initial evaluation period, participants who were diagnosed with IgAN, had urine protein ≥1 g/d, an estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73m2, and were on stable renin-angiotensin system inhibitors were randomly assigned in a 3:1:3 ratio to ALXN2050 180mg, ALXN2050 120mg, or placebo. Investigators measured the primary endpoint as the percent change in urine protein from baseline to week 26, through 24-hour urine collection.

Of the 61 enrolled patients, 47 (77.0%) completed the initial evaluation period. At baseline, mean urine protein was similar between the ALXN2050 and placebo groups (2.2 vs 2.1 g/d), as was mean eGFR (65.9 vs 70.6 mL/min/1.73m²).

By week 26, patients receiving ALXN2050 180 mg had a 26.2% reduction in urine protein compared with a 10.3% reduction with placebo, corresponding to a relative treatment effect of −17.7% (90% CI, −37.5% to 8.3%), with similar findings in sensitivity analyses. When all ALXN2050 doses were combined, the relative treatment effect was −18.6% (90% CI, −37.0% to 5.1%).

Investigators paused the phase 2 study after a serious adverse event in the lupus nephritis cohort, with a patient exhibiting jaundice and marked liver enzyme elevation consistent with acute hepatic failure, resulting in a fatal outcome. Ultimately, the trial was terminated with concerns regarding confounded data when it came to re-initiating dosing.

In the IgAN cohort, most adverse events during the initial evaluation period were mild and unrelated to treatment, and no serious treatment-related adverse events or discontinuations occurred. However, during the extension period, a patient receiving ALXN2050 180 mg experienced liver enzyme elevation with a positive rechallenge signal.

“It’s also important to talk about trials like this. We often hear about positive results and successful recruitment, but many trials encounter safety issues or disappointing efficacy,” said Norouzi. “These trials still matter; they help us learn, refine study design, and understand which therapeutic pathways are worth pursuing. This is how we continue navigating treatment development in IgA nephropathy.”

Editors’ note: Norouzi has relevant disclosures with Calliditas, Novartis, Otsuka, and Boehringer Ingelheim.

Roccatello D, Sayna Norouzi, Mohsen El Kossi, et al. Efficacy and Safety of ALXN2050 in IgAN: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. 

Journal of the American Society of Nephrology

‌Caravaca-Fontán F, Gutiérrez E, Sevillano ÁM, Praga M. Targeting complement in IgA nephropathy. 

The phase 2 study of ALXN2050 in IgAN did not meet its proteinuria endpoint, with emerging safety concerns and early termination.


Sayna Norouzi, MD

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