Immunoglobulin A nephropathy (IgAN), also called Berger's disease, is an autoimmune disease that damages your kidneys. This condition happens when antibodies (specifically IgA) build up and form clumps in your kidneys. These clumps of antibodies can activate different pathways in your body, causing inflammation that damages the kidneys (nephropathy) over time.
Atrasentan (Vanrafia) was approved in 2025 for the treatment of IgAN in people who are at risk of their disease getting worse quickly. It belongs to a class of medicines called endothelin receptor antagonists, which work by blocking receptors (endothelin receptors) that cause inflammation and kidney damage, thus slowing down the disease. Vanrafia is currently the only endothelin receptor antagonist approved to treat IgAN that does not have a risk evaluation and mitigation strategy (REMS) program in place. REMS programs are put in place by the FDA for medicines that have serious safety concerns to help make sure they are used safely.
How Is IgAN Usually Managed, and Where Does Vanrafia Fit In?
A group of kidney experts, called KDIGO, publishes recommendations on how to treat many different kidney diseases, including IgAN. KDIGO makes recommendations based on data from studies on the best ways to care for people with IgAN. Some of their main recommendations are described below.
- Blood pressure control: Ideally, all people with IgAN should have their blood pressure controlled. There has been some debate about what the "goal" blood pressure should be, but generally, the systolic blood pressure (top number) should be less than 130 mm Hg. There are many types of medicines that can be used to lower blood pressure.
- Angiotensin-converting enzyme (ACE) inhibitors (for example, captopril, lisinopril, and ramipril)
- Angiotensin receptor blockers (ARBs, such as irbesartan, losartan, and valsartan)
- Calcium channel blockers (for example, amlodipine and nifedipine)
- Diuretics or "water pills" (for example, chlorthalidone and hydrochlorothiazide)
- Lowering of protein in the urine (proteinuria): For people with high levels of protein in the urine (pee), treatment with an ACE inhibitor or ARB is recommended, even if you do not have high blood pressure. Sometimes other medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors (such as canagliflozin, dapagliflozin, and empagliflozin) are also used to treat proteinuria in people with diabetes.
- Lifestyle modification: Dietary changes (such as lowering the amount of salt you eat), exercise, quitting smoking if you are a smoker, and weight control are all part of a healthy lifestyle and are recommended as a natural way to help control your blood pressure.
- Lowering the risk of heart problems: Lifestyle modification, along with using medicines to lower your cholesterol when needed, are recommended to lower your risk of heart problems.
Vanrafia is approved to treat IgAN in people who are at high risk of their disease getting worse. KDIGO defines "high risk" as having proteinuria (urine protein levels above 0.75 to 1 gram per day, or g/d) after following the recommendations above for at least three months.
How Was Vanrafia Studied for IgAN?
A clinical trial called the ALIGN trial studied how well Vanrafia worked and how safe it was for adults with IgAN. People in the ALIGN trial were at high risk of their IgAN getting worse. Following recommendations like those from KDIGO above, this meant that they had to have IgAN and proteinuria and have been treated with an ACE inhibitor or ARB for at least three months before the study started. A small number of people (less than 5% of the total number of people in the study) who could not take ACE inhibitors or ARBs were also allowed to take part. People in the study were treated with Vanrafia 0.75 mg by mouth once daily or a placebo that looked like Vanrafia but did not contain any medicine.
The main trial included 135 people in the Vanrafia group and 135 people in the placebo group. Of these people, the average age was about 45 years and 59% were male. About 57% of the people were Asian, 36% White, 2% Black or African American, and 5% reported a race of "other." People in the ALIGN trial had IgAN for an average of 5.5 years before enrolling in the study. Around 98.5% of people in the study were taking an ACE inhibitor or ARB, and about 60% had high blood pressure. A small group of 64 people receiving SGLT2 inhibitors were also included in the trial and analyzed separately.
The researchers looked at how well Vanrafia worked by seeing how much the urine protein-creatinine ratio went down after 36 weeks of treatment. The urine protein-creatinine ratio measures how much protein and creatinine are in your urine; a higher number can be a sign of kidney damage.
What Benefits of Vanrafia Were Seen?
After 36 weeks of treatment, the urine protein-creatinine ratio went down by 38% in people who took Vanrafia, compared to a 3% reduction in people who took the placebo. Similar numbers were seen in people who were taking SGLT2 inhibitors during the study.
Your results may differ from what was seen in clinical studies.
What Do We Know About the Long-Term Effectiveness of Vanrafia?
Vanrafia was approved through the FDA via accelerated approval. Medicines that qualify for accelerated approval are ones that are used to treat serious medical conditions when there is an unmet need for treatment of that disease (for example, when no other medicine is available). When a medicine is approved via accelerated approval, the FDA requires the medicine to be studied more after approval to prove that it helps to treat what it is approved for. If those extra studies do not show a benefit, the FDA may take away the approval of that medicine.
In the ALIGN trial, the urine-creatinine ratio was measured early to see if it could predict whether Vanrafia might slow down the process that causes kidney damage from IgAN over time. The ALIGN trial is still happening, and longer-term results are expected sometime in 2026. These results will show whether the lowered urine-creatinine ratio translates to an actual slowing of kidney damage over a longer period of time. Based on those results, the FDA will decide whether Vanrafia should continue to be available.
What Types of Drug Interactions Can Happen?
Several medicines can interact with Vanrafia. These interactions can decrease how well Vanrafia works or increase your risk of side effects.
One type of medicine that Vanrafia interacts with is called organic anion transporting polypeptide (OATP)1B1/1B3 inhibitors. When Vanrafia is taken together with OATP1B1/1B3 inhibitors, it can increase your risk of side effects from Vanrafia.
Vanrafia also interacts with medicines that are called strong or moderate inducers of CYP3A. When Vanrafia is taken with these CYP3A inducers, it may not work as well to treat your IgAN.
Ideally, Vanrafia should not be taken together with OATP1B1/1B3 inhibitors or strong or moderate CYP3A inducers. If you are unsure if you are taking one of these medicines, talk to your pharmacist or other health care provider.
This is not a complete list of interactions. Tell your pharmacist or health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them know if there are any interactions with Vanrafia or if you need the dosage adjusted.
What Should I Know About Vanrafia if I am Pregnant or Can Become Pregnant?
Vanrafia can cause serious birth defects if taken during pregnancy. If you can become pregnant, you should have a negative pregnancy test before starting Vanrafia. You should not start Vanrafia if you are pregnant and should not continue to take it if you become pregnant or plan to become pregnant. Avoid pregnancy for at least two weeks after stopping Vanrafia.
You can become pregnant if you are a female who has started puberty (even if it is before the first menstrual period), have a uterus, and have not gone through menopause yet.
You cannot become pregnant if you (any of the following may apply).
- Have not yet started puberty
- Do not have a uterus
- Have completed menopause (have not had a menstrual period for 12 months or more)
- Have had your ovaries removed
- Have permanent, irreversible infertility (permanently unable to get pregnant) for any other medical reason
If you can become pregnant, you must use effective birth control before starting Vanrafia, during treatment, and for two weeks after you stop taking it. Your health care provider or gynecologist can help you select the right form of birth control for you.
If you are taking Vanrafia and have unprotected sex or think your birth control has failed, contact your health care provider right away. They may suggest a form of emergency birth control. If at any point during treatment you miss a period or think you may be pregnant, contact your health care provider right away.
Getting Your Medicine: What to Expect
Vanrafia is considered a specialty medicine, which is a high-cost medicine that is taken for rare, complex, or chronic diseases. It requires a different process than picking up a prescription at your local pharmacy. This process helps you stay on track with your treatment. The drugmaker has a program to help support the process.
Here are some differences that you may expect.
Insurance approval. Your insurance may require approval for using this medicine, also called a prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered.
Pharmacy access. You will use a specific pharmacy to get your medicine. Your health care provider will work with you and the drugmaker on which pharmacy to use and the information that will be provided. The pharmacy will work with your insurance company to determine the costs. They will also talk with you each month to review your treatment and schedule your delivery.
Copay assistance. There is a copay assistance program from the drugmaker that may allow you to pay $0 for your prescription. For questions or more information, you can contact the drugmaker at 844-482-6723 or visit www.vanrafia.com/savings-support/novartis-patient-support#financial-support.