Novel Targeted Therapies for IgAN: What You Need to Know

IgA nephropathy (IgAN), or Berger’s disease, is a kidney condition that occurs when abnormal immunoglobulin A (IgA) antibodies trigger inflammation in the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e59762960e9eca9-4ac8-42e5-87a9-4dbfc72db5b7 Until recently, treatment for IgAN focused mainly on controlling symptoms with blood pressure medications like angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) , along with lifestyle changes to help protect the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295b775c4d-143f-4aac-9108-cb08a193888d To decrease kidney inflammation, nephrologists (kidney specialists) often prescribe steroids like prednisone, but these medications can cause significant side effects.e60dc2a1-f33c-4a05-9b50-8e3e8e59762929eb89db-43c1-4aea-9e11-934d33676123 In recent years, researchers have developed targeted therapies designed to interfere with processes in the body that lead to IgAN. These focused treatments help protect kidney function and make the condition more manageable for many people.e60dc2a1-f33c-4a05-9b50-8e3e8e59762903a80ff4-0cb1-44c5-b18b-cc749ce15369 Because they aren’t absorbed throughout the entire body, these newer therapies often cause fewer unwanted side effects. We asked experts to explain how these novel targeted therapies work and what you should discuss with your nephrologist if you’re interested in trying new treatment options.
How Targeted Therapies Are Different Targeted Therapies Overview Standard treatments for IgAN help protect the kidneys, but they don’t directly address the immune changes causing ongoing damage. For example, medications like ACE inhibitors and ARBs help lower pressure in the kidneys’ filtering units, which can reduce protein leakage into the urine ( proteinuria ) and slow kidney damage.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292790c627-e05e-4bf1-8cb2-a2f42614c51c “Traditional steroids circulate in the bloodstream and suppress the immune system throughout the body, [but that] leads to a higher risk of side effects such as infections, diabetes , weight gain, and bone loss,” says Stefanie Diaz, MD , a board-certified nephrologist and a member of the teaching faculty at the University of Texas in Tyler. Targeted therapies take a different approach. Instead of managing symptoms, these treatments intervene in the specific processes that contribute to damage in IgAN, whether that’s by reducing the production of abnormal IgA antibodies or blocking inflammation in the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e597629d89e5b80-d001-4050-a170-3c9e88fddaf1 A key goal of targeted therapies for IgAN is to reduce proteinuria.e60dc2a1-f33c-4a05-9b50-8e3e8e597629d89e5b80-d001-4050-a170-3c9e88fddaf1 Damage to the kidneys’ filtering units, which occurs with IgAN, allows protein to leak into the urine, and higher protein levels in the urine are linked to faster loss of kidney function, says Dr. Diaz. Lowering protein in the urine helps protect these filters and may slow disease progression, which is why proteinuria is a key measure in studies of newer IgAN treatments.e60dc2a1-f33c-4a05-9b50-8e3e8e5976294e5989ae-0cb9-4603-a27e-0bf813b56979 Because these treatments target specific areas involved in the disease, rather than suppressing the entire immune system, studies have shown that they may cause fewer side effects than traditional steroids while still lowering proteinuria.e60dc2a1-f33c-4a05-9b50-8e3e8e597629d89e5b80-d001-4050-a170-3c9e88fddaf1 These newer targeted therapies are expanding the treatment options for people with IgAN and giving many people more ways to slow kidney damage. Here are a few that are currently available.
Targeted-Release Steroid Targeted-Release Steroid In 2021, the U.S. Food and Drug Administration (FDA) approved a targeted-release formulation of budesonide (Tarpeyo) for IgAN treatment.e60dc2a1-f33c-4a05-9b50-8e3e8e5976299e6fa8df-e93a-498d-9db7-a59317e900ba Budesonide is a type of steroid, also called a glucocorticoid, that has long been used to reduce inflammation.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295c494e12-67aa-4745-a323-70ada35bff01 What makes this formulation different is where and how it works in the body.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292ad92b5f-f14b-46d2-a674-d70a19d49198 How Targeted-Release Budesonide Works Experts believe that many of the changes that lead to IgAN start in a section of the small intestine where IgA antibodies are produced.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a4e04323-404b-47ef-9dfd-a4387a68585e In IgAN, poorly formed IgA antibodies travel through the bloodstream and become trapped in the kidneys, triggering inflammation. “The goal of targeted-release budesonide is to delay the release of the medication until it reaches the small intestine,” says Erika Gray, PharmD , a pharmacist based in Utah. Once there, budesonide reduces inflammation in the gut tissue where IgA antibodies are generally produced, which helps decrease the amount of abnormal antibodies traveling to the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292ad92b5f-f14b-46d2-a674-d70a19d49198 This targeted approach also means that the medication doesn’t affect your whole body the way traditional steroids like prednisone do.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 In one study, adults taking targeted-release budesonide had a 31 percent reduction in proteinuria after nine months, and the medication helped slow the decline in kidney function over two years.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Targeted-release budesonide is a pill you take by mouth as a nine-month treatment course, unlike many kidney medications you might take long term.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Who Is Eligible for Targeted-Release Budesonide? To qualify for targeted-release budesonide, you must be an adult with primary IgAN who is at high risk of your kidney function worsening, says Jennifer Gershman, PharmD, a pharmacist based in Florida.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Primary IgAN means that the condition developed on its own, without another underlying disease causing it.e60dc2a1-f33c-4a05-9b50-8e3e8e5976296064c075-95ff-4020-9233-06319600a4c0 A high risk of worsening kidney function is primarily determined by persistent proteinuria — at least 1 gram of protein in the urine over 24 hours — despite being on optimized supportive care, including blood pressure control and potentially using other medications like sodium-glucose cotransporter 2 (SGLT2) inhibitors , says Diaz. Your nephrologist will consider your kidney function when determining if this medication is right for you. Targeted-release budesonide may not be recommended if you have severe liver disease, active infections, poorly controlled diabetes, or high blood pressure.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Taking nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen along with targeted-release budesonide can increase the risk of bleeding in the stomach or intestines, says Diaz. You’ll need to avoid grapefruit juice and certain medications, such as ketoconazole (Nizoral), ritonavir (Norvir), and erythromycin (Ery-Tab, Erythrocin), as these can interfere with how budesonide is processed in your body.e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Common Side Effects The most common side effects of targeted-release budesonide include the following:e60dc2a1-f33c-4a05-9b50-8e3e8e597629503b1456-8944-419e-9ff2-c48ae8a5d451 Swelling in the hands, feet, or legs High blood pressure Muscle spasms Acne Headache Upper respiratory infections Weight gain Upset stomach Rash Joint pain Increased white blood cells
Dual Receptor Blocker Dual Receptor Blocker Another targeted therapy for IgAN is sparsentan (Filspari), which was approved by the FDA in 2023.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c862b516-3a27-4856-8150-9ab27ade80b7 Unlike targeted-release budesonide, which works in the immune system in the gut, sparsentan works directly in the kidneys to reduce inflammation and protein leakage in the urine.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295007af1a-bbe3-4213-a011-a0bd29796193 How Sparsentan Works Sparsentan is a pill taken once daily by mouth that helps block two receptors in the kidneys: endothelin type A (ETA) and angiotensin II type 1 (AT1) receptors.e60dc2a1-f33c-4a05-9b50-8e3e8e5976295007af1a-bbe3-4213-a011-a0bd29796193 ETA receptors cause blood vessels to tighten and promote inflammation, which can increase pressure inside the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e597629b843a9e9-84f9-4486-8794-0ef28ea33a0d AT1 receptors increase blood pressure, which can increase strain on the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e597629f79d6c9e-8372-476a-9bc4-bb1802f826e9 By blocking both of these receptors, sparsentan helps blood vessels in the kidneys relax and lowers pressure in the kidneys’ filters, says Pranav Garimella, MBBS, MPH , a nephrologist in San Diego and the chief medical officer at the American Kidney Fund. This dual action lowers proteinuria more effectively than medications that target just one pathway, he says. In a clinical trial, adults taking sparsentan had a 45 percent reduction in proteinuria after 36 weeks.e60dc2a1-f33c-4a05-9b50-8e3e8e597629845840d6-2d8f-4bed-81f5-6282eb789ff2e60dc2a1-f33c-4a05-9b50-8e3e8e59762938ef95df-125e-4910-9144-4121e1780ef5 Over about two years, sparsentan also helped slow kidney function decline. Who Is Eligible for Sparsentan? This medication is approved for adults with primary IgAN whose kidney function is likely to worsen over time without treatment, says Dr. Garimella. Sparsentan can be especially helpful if you can’t tolerate steroids or SGLT2 inhibitors, or if protein levels in your urine remain high despite SGLT2 inhibitor treatment, says Garimella. Combining sparsentan with ACE inhibitors, ARBs, other endothelin blockers, or a medication called aliskiren can cause dangerously low blood pressure. Your nephrologist will help you safely stop an ACE inhibitor or ARB before starting sparsentan and will review your other medications to make sure there are no conflicts. Medications that can interfere with how well sparsentan works include some seizure medications, antibiotics, and antifungals. If you take NSAIDs, your care team will monitor your kidney function more closely.e60dc2a1-f33c-4a05-9b50-8e3e8e597629845840d6-2d8f-4bed-81f5-6282eb789ff2 Sparsentan isn’t recommended during pregnancy because it can harm a developing baby. It’s also not used in people with severe liver disease.e60dc2a1-f33c-4a05-9b50-8e3e8e597629845840d6-2d8f-4bed-81f5-6282eb789ff2 Common Side Effects The most common side effects of sparsentan include the following:e60dc2a1-f33c-4a05-9b50-8e3e8e597629845840d6-2d8f-4bed-81f5-6282eb789ff2 High potassium levels Low blood pressure Swelling in the legs, ankles, or feet Dizziness or lightheadedness Anemia (low red blood cell count) Kidney injury Elevated liver enzymes
ETA Receptor Blocker ETA Receptor Blocker While sparsentan blocks both ETA and AT1 receptors, atrasentan (Vanrafia) is a targeted therapy that focuses only on ETA receptors. In 2025, it received FDA approval to treat IgAN.e60dc2a1-f33c-4a05-9b50-8e3e8e597629a24163bc-6e35-4c1d-8bc6-50b57a1860e7 How Atrasentan Works By blocking ETA receptors, atrasentan helps decrease stress on the kidneys, which can reduce inflammation and lower proteinuria without suppressing your immune system, says Garimella. In a study, adults taking atrasentan had a 38 percent reduction in proteinuria after 36 weeks, compared with a 3 percent reduction in those taking a placebo (a pill containing no medication).e60dc2a1-f33c-4a05-9b50-8e3e8e5976294c98bda0-cd58-401a-9a40-681e68d34d46 All study participants continued standard supportive care, such as ACE inhibitors or ARBs, and some also took SGLT2 inhibitors. Atrasentan is a pill taken once a day by mouth. Although it helps lower proteinuria, researchers are still determining whether it also slows long‑term loss of kidney function.e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 Who Is Eligible for Atrasentan? To be eligible for atrasentan, you must be an adult with primary IgAN at risk for faster disease progression.e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 This typically means having proteinuria, measured as a urine protein-to-creatinine ratio (uPCR) of 1.5 grams per gram or higher, despite receiving supportive care.e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 UPCR is a spot test that measures protein leakage in the urine. Your nephrologist will consider your proteinuria, kidney function, and overall health to see if this treatment is appropriate for you. Atrasentan can be added to ACE inhibitors and ARBs, whether or not you’re also taking an SGLT2 inhibitor, says Garimella. It’s also an option if you want to avoid immunosuppressive medications like steroids, or if you’ve had liver‑related side effects with sparsentan, he says. Some medications can interfere with how atrasentan works. These include certain antibiotics and seizure medications. Others, like the antifungal drug ketoconazole, can cause higher amounts of the medication to build up in your body.e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 Let your nephrologist know about all medications and supplements you take. Atrasentan can cause serious harm to a developing baby, so it’s not recommended if you’re pregnant or planning to become pregnant.e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 People who can become pregnant should use effective birth control while taking this medication and for two weeks after stopping treatment. Common Side Effects Common atrasentan side effects include the following:e60dc2a1-f33c-4a05-9b50-8e3e8e59762948d9feb1-264f-455e-b56b-76e5f430c180 Swelling in the legs, ankles, or feet Anemia Fluid retention Elevated liver enzymes
Complement System Inhibitor Complement System Inhibitor The medication iptacopan (Fabhalta) received FDA approval for IgAN treatment in 2024.e60dc2a1-f33c-4a05-9b50-8e3e8e597629ffc2bc09-156f-4530-957e-7f09ef536ca3 Iptacopan helps treat IgAN by acting on a part of the immune system called the complement system.e60dc2a1-f33c-4a05-9b50-8e3e8e597629af8ba4ed-b25c-4c0c-a5c6-863fb6fb6fa8 How Iptacopan Works The complement system is a group of proteins in your blood that help the body fight infections and clean up damaged cells.e60dc2a1-f33c-4a05-9b50-8e3e8e59762913f9f6a6-cb68-4738-9847-9c705a4b21cf In IgAN, this system can become overactive, adding to inflammation and injury in the kidneys.e60dc2a1-f33c-4a05-9b50-8e3e8e5976290cda6dc3-0252-40cc-9901-bfe406c577c6 Iptacopan blocks a specific step in the complement system, which reduces ongoing inflammation in the kidneys without weakening the immune system overall, says Garimella. In a clinical trial, adults who took iptacopan for nine months had uPCR levels that were 38 percent lower than in those taking placebo.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293f67537b-3f94-45fb-9ca7-cda28be626bb The study participants also received standard supportive care, such as ACE inhibitors or ARBs, with some participants taking SGLT2 inhibitors, too. Iptacopan is a pill that’s taken by mouth twice a day, and while it has been shown to reduce proteinuria in people with IgAN, researchers are still studying whether it slows long‑term kidney function decline.e60dc2a1-f33c-4a05-9b50-8e3e8e597629627f7c26-f2fd-49b2-a39a-5c8ac559fd6b Who Is Eligible for Iptacopan? Adults with primary IgAN who are at high risk for faster disease progression may be candidates for this treatment. This typically includes people with a uPCR of 1.5 grams per gram or higher, even after receiving standard supportive care.e60dc2a1-f33c-4a05-9b50-8e3e8e597629627f7c26-f2fd-49b2-a39a-5c8ac559fd6b Your nephrologist will evaluate your proteinuria levels, kidney function, and overall health when deciding if this therapy is appropriate. Because iptacopan affects part of the immune system, you must receive certain vaccines before treatment begins. These include vaccines against meningococcal, pneumococcal , and Haemophilus influenzae type b infections, and the medication isn’t used during an active infection with these bacteria.e60dc2a1-f33c-4a05-9b50-8e3e8e597629627f7c26-f2fd-49b2-a39a-5c8ac559fd6b Common Side Effects The most common side effects of iptacopan include the following:e60dc2a1-f33c-4a05-9b50-8e3e8e597629627f7c26-f2fd-49b2-a39a-5c8ac559fd6b Headache Common cold Diarrhea Abdominal pain Infections Nausea Joint pain Dizziness High blood pressure Increased cholesterol or triglycerides Rash The most serious side effect of iptacopan is a dangerous infection from the bacteria discussed above, which is why the required vaccinations and regular follow-ups with your nephrologist are important.e60dc2a1-f33c-4a05-9b50-8e3e8e597629627f7c26-f2fd-49b2-a39a-5c8ac559fd6b
Monoclonal Antibody Monoclonal Antibody One of the most recently FDA-approved targeted therapies for IgAN is sibeprenlimab (Voyxact), which received approval in November 2025.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293bc10f81-d397-4c02-9385-4dc8cca1119f Sibeprenlimab belongs to a class of medication known as monoclonal antibodies and targets the production of abnormal IgA antibodies.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e2009c11-667a-45fe-a477-d5529f76231c Unlike the other targeted therapies discussed earlier, sibeprenlimab is given by injection rather than a pill. How Sibeprenlimab Works Sibeprenlimab blocks a protein in the immune system called a proliferation-inducing ligand (APRIL), which helps certain immune cells make antibodies. In IgAN, APRIL contributes to the production of abnormal IgA antibodies that lead to kidney inflammation. By preventing APRIL from doing its job, sibeprenlimab helps lower the amount of these abnormal antibodies being produced, which can decrease kidney inflammation and reduce proteinuria.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e2009c11-667a-45fe-a477-d5529f76231c In one study, adults taking sibeprenlimab had about a 50 percent reduction in proteinuria after nine months.e60dc2a1-f33c-4a05-9b50-8e3e8e5976292bbe1bc0-3ef8-4e71-9927-89c340ecae78 Study participants continued standard supportive care, such as ACE inhibitors or ARBs, and about 40 percent were also taking SGLT2 inhibitors. Sibeprenlimab is given as an injection under the skin every four weeks.e60dc2a1-f33c-4a05-9b50-8e3e8e597629c9538b66-15fd-466f-8942-3645151529e7 Researchers are still studying whether this medication can help slow long-term kidney function decline, though it has been shown to significantly reduce proteinuria.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e2009c11-667a-45fe-a477-d5529f76231c Who Is Eligible for Sibeprenlimab? Similar to the treatments previously discussed, sibeprenlimab is approved for adults with primary IgAN who are at risk for disease progression.e60dc2a1-f33c-4a05-9b50-8e3e8e597629e2009c11-667a-45fe-a477-d5529f76231c Your nephrologist will look at multiple factors to determine if sibeprenlimab is appropriate, including your proteinuria levels, kidney function, and overall health status. Sibeprenlimab can increase the risk of infection. Make sure to tell your care team about any infections before starting treatment. Live vaccines (which contain weakened forms of viruses, such as the chickenpox and nasal spray flu vaccines) aren’t recommended during treatment with sibeprenlimab, as the medication may interfere with how the vaccines work.e60dc2a1-f33c-4a05-9b50-8e3e8e5976293bc10f81-d397-4c02-9385-4dc8cca1119f Common Side Effects Sibeprenlimab side effects include the following:e60dc2a1-f33c-4a05-9b50-8e3e8e597629e2009c11-667a-45fe-a477-d5529f76231c Serious infections, including upper respiratory infections Injection‑site reactions
Seeing a Doctor Seeing a Doctor Whether one of these targeted therapies is right for you depends on your overall health and preferences. Start by having a conversation with your nephrologist. Here are some steps to take to prepare for your appointment: Gather your recent lab results, especially your eGFR and proteinuria levels Write down all medications you take, including over-the-counter drugs, vitamins, and supplements Make a list of any health conditions you have, especially liver problems, diabetes, high blood pressure, or active infections Note your vaccination history, particularly for meningococcal, pneumococcal, and Haemophilus influenzae type b vaccines Consider your lifestyle and whether a daily pill, twice-daily pill, monthly injection, or specific treatment course would work better for you Some questions you might want to ask your nephrologist include the following: Based on my proteinuria levels and kidney function, which targeted therapies am I eligible for? What are the main differences between these treatments in terms of how they work and potential side effects? Would a pill or an injection fit my lifestyle and health situation better? Are there any medications I’m currently taking that would prevent me from using certain treatments? How long would I need to stay on each treatment option? What kind of monitoring will I need with each therapy? What results should I expect, and how long before we know if the treatment is working? It’s also helpful to set realistic expectations. Targeted therapies may help slow kidney damage, reduce proteinuria, and preserve kidney function, but they don’t cure IgAN.e60dc2a1-f33c-4a05-9b50-8e3e8e59762932c26617-ac47-474a-9e57-a58af7c0fe01 Healthy lifestyle habits are still important along with medication, says Diaz. These include limiting sodium, avoiding smoking, staying physically active, and maintaining a healthy weight to support long-term kidney health, she says. Still, these targeted treatments represent exciting new options that offer hope for people with IgAN whose disease remains active despite standard care.
The Takeaway Targeted therapies for IgA nephropathy focus on specific processes that cause the disease. They can help reduce proteinuria and potentially slow disease progression with fewer side effects than traditional steroids. Targeted-release budesonide targets antibody production in the gut, while iptacopan blocks a specific inflammation pathway. Sparsentan and atrasentan block inflammation in the kidneys, while sibeprenlimab is an injection that prevents abnormal antibodies from forming. Talk with your nephrologist about whether a targeted therapy is right for you, as these medications may offer new hope for slowing disease progression when paired with supportive care and healthy lifestyle habits.
Resources We Trust Mayo Clinic: Diagnosed With IgAN? Here’s What to Know About Your Treatment OptionsCleveland Clinic: IgA Nephropathy: Reviewing the Evidence on Current and Future TherapiesIgA Nephropathy Foundation: Treatment Options National Kidney Foundation: IgA Nephropathy (IgAN)UNC Kidney Center: IgA Nephropathy