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Historically, the global population with kidney disease — 850 million people, at present — has had few options to slow or halt progression to end-stage renal disease. The medications used most — ACE inhibitors, angiotensin receptor blockers and other blood-pressure drugs — can help preserve kidney function but were not originally developed to treat kidney disease. Even a major cornerstone of kidney disease management, SGLT2 inhibitors, was initially developed to treat type 2 diabetes.
But after decades of stagnation in the development of kidney disease drugs, a wave of experimental therapies is beginning to reshape the field (Table 1). This reflects both new insights into kidney disease biology and growing confidence among regulators that surrogate endpoints such as proteinuria (the presence of protein in the urine) can be predictive of long-term outcomes.
At the same time, other companies are pursuing entirely different strategies — from genetically targeted therapies to drugs that block the complement cascade, a part of the immune system that can go into overdrive and damage the kidney. These efforts signal a broader transformation in how researchers think about treating kidney disease.
“It’s been fantastic. We are getting new molecules all the time,” says Swapnil Hiremath, a nephrologist at the Ottawa Hospital in Canada.
From blood pressure to molecular targeting
These efforts reflect a fundamental change in how kidney diseases are approached in the clinic. Rather than relying on broadly acting therapies such as blood-pressure control, researchers are now developing drugs that intervene directly in the molecular pathways that damage the kidney.
The approaches vary widely, but they share a common premise: that understanding the molecular drivers of kidney disease can reveal targets for therapy. If successful, they could transform a field that has long struggled to produce new medicines. A turning point came in July 2025, when the US Food and Drug Administration (FDA) approved pegcetacoplan — demonstrating that a kidney drug could do more than slow the decline in kidney function, with biopsies showing resolution of disease in about 70% of treated patients within 6 months.
Nowhere is the renal renaissance more apparent than in treatments for IgA nephropathy, an autoimmune condition that causes large clumps of IgA antibodies to build up in the delicate blood vessels of the kidney, which leads to renal damage and failure. Multiple late-stage drugs that target different parts of the immune system are racing toward approval for this crippling condition. The pharmaceutical push began in 2019, when the FDA first approved a reduction in proteinuria as a surrogate endpoint for the condition.
Historically, clinical trials relied on measuring a slowing of the rate of kidney failure, but this required at least 2 years of follow-up to provide detectable results. The FDA’s acceptance of decreasing proteinuria as a surrogate for kidney function rapidly sped up interest in drug development, Hiremath says. Five drugs for treating IgA nephropathy have already been approved, and more are nearing the finish line.
Several new treatments for IgA nephropathy focus on calming the immune cells known as B cells that produce abnormal IgA antibodies. Many of the leading experimental drugs target immune signaling molecules called cytokines — in particular, BAFF and APRIL — which promote the survival and growth of B cells. By dialing down these signals, researchers aim to reduce levels of harmful IgA complexes.
Vera Therapeutics’ atacicept is a fusion protein that blocks both BAFF and APRIL, selectively inhibiting the B cells responsible for producing disease‑causing IgA and related autoantibodies. Atacicept is highly selective, so it leaves patients with an otherwise intact immune system.
In the company’s phase 3 ORIGIN trial, patients receiving atacicept experienced substantially greater reductions in proteinuria than those who received placebo, without a heightened risk of infection or immunocompromise.
“Normalizing the trajectory of kidney function over 2 years is a transformative result. This is a really big deal in terms of efficacy,” says Marshall Fordyce, founder and chief executive officer of Vera. “At the right dose, atacicept can normalize the immune system, not just deplete B cells.”
Like atacicept, Vertex’s povetacicept also targets both BAFF and APRIL. In a recent phase 3 study of IgA nephropathy, patients treated with the drug experienced about a 52% reduction in proteinuria after 36 weeks, compared with only a small reduction in the placebo group. At the same time, levels of disease-associated antibodies fell sharply in the treatment group.
The company plans to seek regulatory approval on the basis of these results while continuing longer-term follow-up to determine whether the therapy slows loss of kidney function. Both Vera and Vertex have already begun investigating whether atacicept and povetacicept can target other autoimmune renal conditions, such as lupus nephritis.
Still another strategy targets a later stage of the same immune process. Rather than modifying B cell signaling, Biogen’s approach focuses on plasma cells — the descendants of B cells that actively generate disease‑causing IgA.
The company’s drug, felzartamab, is a monoclonal antibody designed to eliminate CD38+ plasma cells, which are thought to be a key source of the IgA complexes that accumulate in the kidney.
Eliminating these specific cells may reduce immunocomplex formation and the resulting kidney inflammation, according to Uptal Patel, head of Biogen’s West Coast Hub in San Francisco. The drug is currently being evaluated in late-stage trials in patients whose disease persists despite standard therapy.
“Felzartamab was designed specifically for people with immune mediated diseases,” says Patel. “And that makes it much better tolerated”.
Slower scarring
But antibodies are only one part of the story. Once deposited in the kidney, these immunocomplexes can activate other inflammatory pathways, including the complement system, an immune cascade that normally helps fight infection but can mistakenly drive inflammation and scarring in the kidney. Complement activation leads to renal inflammation and cellular damage, which makes this an attractive target for various drugs used to treat kidney disease.
Pegcetacoplan, developed by Apellis Pharmaceuticals and then acquired by Biogen, treats rare disorders characterized by inflammation and progressive kidney damage driven by uncontrolled complement activation. Pegcetacoplan targets C3, a central protein that sits at the convergence point of all complement-activation pathways. Blocking C3 prevents inflammatory signaling that can cause scarring in the kidney’s filtering units.
“We looked at histopathology in these patients with C3 glomerulopathy after 6 months, and in 70% of them, there was no more trace of the disease visible. It was absolutely extraordinary to see that type of efficacy,” says Cedric Francois, co-founder and chief executive officer of Apellis.
Beyond immunity
