Treatments for IgA Nephropathy

According to KDIGO, a worldwide organization developing and implementing evidence-based clinical practice guidelines in kidney disease, effective treatment for IgA nephropathy involves two connected goals.

One is slowing the progression of chronic kidney disease (CKD) through measures that lower proteinuria, protect the kidney filters, and reduce ongoing injury, largely considered supportive care. The other, requiring IgA nephropathy-specific medicines, is reducing the production of galactose-deficient IgA1 (Gd-IgA1) and calming the immune pathways that cause inflammation in the kidneys.

Different treatments work on different parts of this strategy. Supportive therapies such as RAAS blockade, SGLT2 inhibitors, blood pressure control, and lifestyle measures focus on preserving kidney function over time. Medicines that target the immune system aim to reduce the upstream drivers of Gd-IgA1 and its immune effects.

Most people benefit from a combination of these approaches.

The renin-angiotensin-aldosterone system (RAAS) helps control blood pressure and pressure inside the kidney filters. Medicines such as ACE inhibitors (angiotensin converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) lower this internal pressure and reduce protein loss in the urine. Even though they are not approved specifically "for IgA nephropathy" on the label, they are a standard part of care for most people with IgA nephropathy because they help protect kidney function over time.

SGLT2 inhibitors (sodium-glucose cotransporter 2 inhibitors) were first developed to treat diabetes, but they also protect the kidneys. They reduce stress on the filtering units, lower protein leakage, and can slow the decline in kidney function in people with chronic kidney disease. In IgA nephropathy, SGLT2 inhibitors are often added on top of RAAS blockade when kidney function and other factors make their use appropriate, even if the drug label does not mention IgA nephropathy by name.

In the past few years, several medicines have been approved in the United States specifically for adults with primary IgA nephropathy who have persistent proteinuria and are at risk of kidney damage. Most of these approvals are under the FDA's accelerated approval pathway, based on reduction in proteinuria as a marker linked to better long-term outcomes. These drugs are usually added on top of supportive care such as RAAS blockade and SGLT2 inhibitors, not used alone.

• Generic: budesonide (targeted-release / TRF-budesonide)
• Brand: Tarpeyo
• Mechanism: a corticosteroid designed to release mainly in the lower small intestine, where a large part of the immune system involved in IgA nephropathy sits.
• Regulatory status (US): received accelerated approval in 2021 to reduce proteinuria in adults with primary IgA nephropathy; the FDA later granted full (traditional) approval in 2023 after confirmatory data.

• Generic: sparsentan
• Brand: Filspari (FILSPARI)
• Mechanism: blocks both the endothelin A receptor and the angiotensin II type 1 receptor, directly targeting glomerular injury and protein leakage.
• Regulatory status (US): initially received accelerated approval, then in 2024 gained full FDA approval to slow kidney function decline and reduce proteinuria in adults with primary IgA nephropathy at risk of disease progression.

• Generic: atrasentan
• Brand: Vanrafia
• Mechanism: selectively blocks the endothelin A receptor, which is involved in narrowing blood vessels and promoting kidney damage in proteinuric kidney disease.
• Regulatory status (US): received FDA accelerated approval in April 2025 to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression.

• Generic: iptacopan
• Brand: Fabhalta
• Mechanism: an oral inhibitor of complement factor B, targeting the alternative complement pathway, which is thought to contribute to kidney injury in IgA nephropathy.
• Regulatory status (US): received FDA accelerated approval in August 2024 to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression.

• Generic: sibeprenlimab-szsi
• Brand: Voyxact (VOYXACT)
• Mechanism: a monoclonal antibody that targets APRIL (A Proliferation-Inducing Ligand), a signaling protein involved in the abnormal IgA immune response that drives IgA nephropathy.
• Regulatory status (US): received FDA accelerated approval in November 2025 to reduce proteinuria in adults with primary IgA nephropathy; continued approval depends on confirmation that it slows kidney function decline in long-term follow-up studies.

Alongside these drug treatments, other measures are important for nearly everyone with IgA nephropathy. These include carefully controlling blood pressure, limiting salt intake, managing cholesterol, treating anemia when present, maintaining a healthy weight, stopping smoking, and staying current with recommended vaccinations. These steps do not replace disease-specific medicines, but they work together with them to protect kidney function and overall health over time.

Clinical trials give people access to new IgA nephropathy treatments that are not yet widely available. Many trials study medicines that target specific parts of the immune system or complement system involved in IgA production and kidney injury. Others test new ways to reduce proteinuria or protect kidney function. Participation is voluntary, and each trial has its own eligibility criteria based on kidney function, protein levels, and other health factors. Trials help researchers confirm how well new therapies work and whether they can slow long-term kidney damage. For some patients, a clinical trial may offer an option when standard treatments are not enough. Participating in clinical trials also helps patients who are unable to enroll because of health criteria, location, or financial constraints.

These medicines are not approved for routine use and are still undergoing evaluation in phase 1-3 studies. They target different parts of the immune system or complement pathways involved in IgA nephropathy.

To see a list of open clinical trials for IgA nephropathy, refer to the IgA Nephropathy Foundation's up-to-date listing.

Because these treatments are still experimental, the most important questions are whether they can reliably lower proteinuria, help stabilize kidney function, and maintain an acceptable safety profile over time. Some medicines-such as atacicept, telitacicept, and mezagitamab-already have encouraging phase 2-3 results. Others, such as BHV-1400 and PS-002, are earlier in development but aim directly at underlying disease mechanisms.

Access to these therapies is limited to clinical trials, and results from ongoing studies will determine which become future treatment options. Decisions about trial participation should consider kidney function, current treatment response, the demands of trial visits, and personal goals.

The following experimental medicines are grouped by the main part of the immune system they target:

These drugs try to interrupt the overactive B-cell signaling that leads to production of disease-causing IgA and Gd-IgA1. They focus on BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand), two key signals that help B cells survive and mature.

Atacicept (dual BAFF/APRIL fusion protein)

• Mechanism: a fusion protein that blocks both BAFF and APRIL, aiming to reduce production of Gd-IgA1 and other harmful antibodies.
• Key data: in the ORIGIN 3 phase 3 trial, atacicept produced a large and statistically significant reduction in proteinuria (UPCR) at 36 weeks compared with placebo. It also lowered Gd-IgA1 levels, helped resolve hematuria in more patients, and showed a favorable trend in preserving kidney function.
• Status: positive phase 3 data; a biologics license application (BLA) has been submitted, but it is not yet approved for IgA nephropathy.

Povetacicept (long-acting dual BAFF/APRIL biologic)

• Mechanism: a long-acting agent given by subcutaneous injection (typically every 4 weeks) that blocks both BAFF and APRIL.
• Key data: early phase 1/2 IgA nephropathy data show large and sustained reductions in proteinuria with stable eGFR.
• Status: a large phase 3 trial called RAINIER is ongoing to see if these early benefits translate into slower long-term kidney decline.

Telitacicept (TACI-Fc fusion protein)

• Mechanism: a fusion protein that binds and neutralizes both BAFF and APRIL, similar in concept to atacicept but with a different structure.
• Key data: a phase 3 trial in China found that telitacicept produced a substantial reduction in proteinuria (on the order of 50-60% at 39 weeks) compared with single-digit reductions on placebo. Kidney function remained largely stable, and serum IgA and Gd-IgA1 levels fell.
• Status: phase 3 data are positive, but regulatory approval for IgA nephropathy has not yet been granted.

Zigakibart (BION-1301, anti-APRIL monoclonal antibody)

• Mechanism: a monoclonal antibody that blocks APRIL alone, aiming to reduce survival of plasma cells that make Gd-IgA1.
• Key data: phase 2 results show meaningful proteinuria reductions (roughly 50-55%) and stable eGFR over extended follow-up.
• Status: the BEYOND phase 3 trial is underway to confirm efficacy and safety in a larger, global IgA nephropathy population.

These drugs target the complement system, which amplifies inflammation and tissue injury once immune complexes deposit in the kidney. Different agents act at different "checkpoints" in the complement cascade.

Ravulizumab (C5 inhibitor)

• Mechanism: a long-acting monoclonal antibody that blocks complement protein C5, preventing formation of the membrane attack complex and downstream inflammation.
• Key data: in the SANCTUARY phase 2 trial, ravulizumab led to early, sustained, and clinically meaningful reductions in proteinuria compared with placebo, with a trend toward more stable eGFR.
• Status: a dedicated phase 3 IgA nephropathy trial is ongoing to see whether these early signals translate into long-term kidney protection.

Cemdisiran (siRNA to C5)

• Mechanism: a small interfering RNA (siRNA) drug that reduces production of C5 in the liver, lowering circulating C5 and dampening terminal complement activity.
• Key data: in a phase 2 trial, cemdisiran reduced proteinuria at around week 32 and was generally well tolerated, with stable kidney function.
• Status: still investigational; further development (often in combination with other complement agents) is being explored.

Sefaxersen (RO7434656, IONIS-FB-LRx; antisense to complement factor B)

• Mechanism: an antisense oligonucleotide that lowers production of factor B, a key component of the alternative complement pathway.
• Key data: phase 2 data show a roughly 40-45% mean reduction in 24-hour proteinuria at ~29 weeks, with strong suppression of alternative-pathway activity and stable eGFR.
• Status: remains in development; not approved for IgA nephropathy.

ARO-C3 (RNAi therapy targeting complement C3)

• Mechanism: an RNA interference (RNAi) drug given by injection that reduces levels of C3, a central hub in the complement cascade, thereby dampening all downstream complement activation.
• Key data: in early IgA nephropathy cohorts, ARO-C3 produced deep and sustained reductions in C3 and alternative-pathway activity, with meaningful reductions in UPCR and stable kidney function.
• Status: phase 1/2 results are encouraging; additional studies will be needed to define long-term efficacy and safety in IgA nephropathy.

These drugs target plasma cells and other CD38-expressing immune cells that produce large amounts of Gd-IgA1 and related autoantibodies. The goal is to "turn off the factory" making the pathogenic IgA at its source.

Felzartamab (anti-CD38 monoclonal antibody)

• Mechanism: a monoclonal antibody that binds CD38 on plasma cells and other immune cells, leading to their depletion or functional silencing.
• Key data: in the IGNAZ phase 2 study, felzartamab produced rapid and clinically meaningful reductions in proteinuria compared with placebo, with less eGFR decline. Reductions in total IgA and Gd-IgA1 were sustained for well over a year after the last dose, while IgG levels recovered more quickly.
• Status: still investigational; longer-term and larger studies are needed, but the durability of response raises the possibility of disease modification.

Mezagitamab (TAK-079, anti-CD38 monoclonal antibody)

• Mechanism: another anti-CD38 antibody that depletes or functionally suppresses CD38-expressing cells, aiming to reduce production of Gd-IgA1 and other pathogenic antibodies.
• Key data: in a phase 1b IgA nephropathy study, mezagitamab led to ~55% mean reduction in proteinuria and ~50% reduction in Gd-IgA1, with stable eGFR up to 18 months after the last dose. Hematuria resolved in many patients, and IgG levels recovered toward normal while disease-driving markers stayed suppressed.
• Status: a phase 3 program is underway; the early data support the idea that a time-limited course could have long-lasting effects.

Instead of broadly suppressing the immune system, these agents are designed to remove the specific harmful antibody-Gd-IgA1-from the circulation.

BHV-1400 (Gd-IgA1 TRAP degrader)

• Mechanism: a "TRAP degrader" designed to bind Gd-IgA1 in the bloodstream and route it to the liver for clearance, while sparing normal immunoglobulins (IgA, IgG, IgE, IgM). This is a precision approach aimed at the root antibody driver of IgA nephropathy and IgA vasculitis.
• Key data: in a phase 1 study in healthy volunteers, single-dose BHV-1400 produced rapid, deep, and sustained reductions in Gd-IgA1 (median reduction around two-thirds, with some participants showing >80% reduction) without meaningful changes in other immunoglobulins.
• Status: still in early clinical development. Trials in patients with IgA nephropathy are planned but data in IgA nephropathy patients are not yet available; for now, the evidence is primarily from healthy volunteers and preclinical models.

These approaches try to re-program kidney cells or immune pathways at a genetic level, with the goal of more durable disease control.

PS-002 (AAV-based gene therapy delivering complement factor I)

• Mechanism: an adeno-associated virus (AAV) gene therapy that delivers the gene for complement factor I directly to podocytes (specialized kidney cells). By boosting local factor I, the therapy is intended to dampen complement activation in the glomerulus and protect the kidney from ongoing damage.
• Preclinical data: in animal models of IgA nephropathy, PS-002 reduced complement deposition, lowered markers of kidney injury, and improved structural features such as scarring, with sustained gene expression and favorable safety.
• Status: a phase I/II clinical trial in adults with primary IgA nephropathy has received regulatory clearance and is now enrolling, but human efficacy data in IgA nephropathy are not yet available.