Tarpeyo

Tarpeyo is used to reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for their disease getting worse. It is a delayed-release corticosteroid capsule taken once daily for 9 months.

IgA nephropathy, also called IgAN or Berger disease, is a kidney disease in which an antibody called galactose-deficient IgA1 (Gd-IgA1) builds up in the kidneys, causing inflammation that can slowly damage them. Over time, this can lead to chronic kidney disease and, in some people, kidney failure (end-stage renal disease). The Gd-IgA1 antibodies are made mainly by immune cells (B cells) in the lining of the lower small intestine, called the ileum. Tarpeyo is designed to release budesonide in this part of the gut, where it can act on those immune cells.

Tarpeyo (budesonide) first received accelerated FDA approval on December 15, 2021, based on its effect on protein in the urine (proteinuria). It was granted full approval on December 20, 2023, after a trial showed it reduces the loss of kidney function, making it the first treatment approved specifically to slow kidney function decline in IgA nephropathy. Tarpeyo is made by Calliditas Therapeutics AB.

Tarpeyo is approved to reduce the loss of kidney function in adults with primary IgA nephropathy who are at risk for disease progression. It is not known whether Tarpeyo is safe and effective in children.

Budesonide is a corticosteroid with strong anti-inflammatory and immune-calming (immunosuppressive) effects. The immune cells in the ileum that produce the Gd-IgA1 antibodies behind IgA nephropathy carry glucocorticoid receptors. By acting on these receptors, budesonide can reduce the number and activity of those cells, which lowers production of the antibodies that damage the kidneys.

Tarpeyo uses a delayed-release capsule that is built to pass through the stomach and release the medicine in the ileum, targeting the immune cells where the disease begins. The capsule also undergoes substantial breakdown on its first pass through the liver, which helps limit how much steroid reaches the rest of the body, though some systemic steroid effects can still occur.

Tarpeyo was studied in NefIgArd (NCT03643965), a phase 3, randomized, double-blind, placebo-controlled trial in 364 adults with biopsy-confirmed IgA nephropathy who were already taking a maximally tolerated ACE inhibitor or ARB. Participants took Tarpeyo 16 mg once daily or placebo for 9 months, followed by a 2-week taper, and were then followed off treatment through 2 years.

• At 9 months, Tarpeyo reduced protein in the urine (measured by urine protein to creatinine ratio) by about 31% compared with placebo.
• Over 2 years, kidney function (measured by estimated glomerular filtration rate, or eGFR) declined less with Tarpeyo than with placebo, a difference of about 5.9 mL/min/1.73 m2 in favor of Tarpeyo.

The benefit on kidney function seen during the 9-month treatment period persisted after treatment ended, but Tarpeyo did not change the long-term rate of kidney function decline. The safety and effectiveness of repeat courses of Tarpeyo have not been established.

Take Tarpeyo exactly as prescribed. Follow all directions on your prescription label and read any medication guides or instruction sheets.

• Swallow the capsules whole in the morning, at least 1 hour before a meal. Do not open, chew, crush, break, or dissolve a Tarpeyo capsule.
• Do not stop taking Tarpeyo suddenly. If you and your doctor decide to stop, follow the taper instructions below.
• Your dosage needs may change if you have surgery, become ill, or are under stress. Do not change your dose or schedule without your doctor's advice.
• If you take Tarpeyo long-term, you may need regular medical tests, including monitoring for adrenal suppression when tapering.

Important safety information

Tarpeyo is a corticosteroid that is absorbed into the body, so it can cause steroid-related effects. Long-term use can lead to higher-than-normal steroid levels (hypercorticism) and to adrenal gland suppression, where the body cannot make enough of its own stress hormones. Tarpeyo also lowers the body's defenses and raises the risk of infection. Do not stop Tarpeyo suddenly, and follow your doctor's taper instructions.

Do not use Tarpeyo if you are allergic to budesonide or to any of the ingredients in the capsules. Serious allergic reactions, including anaphylaxis, have occurred with other budesonide products.

Because Tarpeyo can weaken your immune system, avoid using it if you have an active or latent (inactive) tuberculosis infection, an untreated fungal, bacterial, systemic viral, or parasitic infection, or herpes simplex of the eye. Chickenpox and measles can be serious or even fatal in people taking corticosteroids who are not immune. Tarpeyo may also reduce how well vaccines work. Tell your doctor about any illness or infection you have had in the past several weeks.

Corticosteroids like Tarpeyo can worsen some existing conditions, including high blood pressure, diabetes or prediabetes, osteoporosis, glaucoma, cataracts, and stomach ulcers. Your healthcare provider will monitor you during treatment.

Kaposi's sarcoma has been reported in people receiving corticosteroid therapy, most often for chronic conditions. Tell your healthcare provider if you experience any signs or symptoms.

People with moderate to severe liver disease may absorb more budesonide and are more likely to have steroid-related effects. Tarpeyo should not be used in people with severe liver disease.

You should not use Tarpeyo if you are allergic to budesonide or any ingredient in the capsules.

To make sure Tarpeyo is safe for you, tell your doctor if you:

• Have liver problems
• Have an infection now, or have had tuberculosis
• Have chickenpox or measles, or have recently been near someone who does
• Have high blood sugar, prediabetes, or diabetes, or a family history of diabetes
• Have glaucoma or cataracts, or a family history of glaucoma
• Have high blood pressure
• Have decreased bone mineral density or osteoporosis
• Have stomach ulcers
• Are a carrier of hepatitis B, or have had hepatitis B
• Have a weakened immune system from disease or from taking certain medicines
• Are pregnant or plan to become pregnant
• Are breastfeeding or plan to breastfeed

Pregnancy

Published studies of oral budesonide in pregnancy have not found a clear link to major birth defects or miscarriage. However, babies exposed to corticosteroids in the womb can have low levels of adrenal hormones (hypoadrenalism) at birth and should be watched closely. IgA nephropathy itself can also raise the risk of problems during pregnancy. Talk with your healthcare provider about the benefits and risks of using Tarpeyo if you are pregnant or planning a pregnancy.

Breastfeeding

Budesonide can pass into breast milk and may harm your baby. If you take budesonide long-term while breastfeeding, your healthcare provider may monitor your baby's growth. Talk with your provider about the best way to feed your baby during treatment.

Get emergency medical help if you have signs of an allergic reaction to Tarpeyo: hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Serious side effects

Tarpeyo may cause serious side effects, including:

• Too much steroid in the body (hypercorticism). Signs include acne, more hair on the body and face, easy bruising, a fatty pad between the shoulders (buffalo hump), a rounded face (moon face), and pink or purple stretch marks on the abdomen, thighs, breasts, or arms.
• Adrenal suppression. With long-term use, the adrenal glands may not make enough steroid hormones. Signs include tiredness, weakness, nausea and vomiting, and low blood pressure. Tell your provider if you are under stress or have these symptoms.
• Weakened immune system and infections. Tarpeyo makes infections more likely. Avoid contact with people who have chickenpox or measles, and tell your provider right away if you are exposed. Watch for signs of infection such as fever, chills, aches, pain, tiredness, and nausea or vomiting.

Common Tarpeyo side effects

The most common side effects, each reported in 5% or more of people in the main study, include:

• Swelling of the hands, legs, ankles, feet, or face (peripheral and facial edema)
• High blood pressure
• Muscle cramps or spasms
• Acne or dermatitis
• Headache
• Upper respiratory tract infection, such as a cold or stuffy nose
• Weight gain
• Indigestion (dyspepsia)
• Joint pain
• An increase in white blood cell count

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to Calliditas Therapeutics at 1-844-IGA-0011 or to the FDA at 1-800-FDA-1088.

Dose of Tarpeyo for IgA nephropathy:

• 16 mg by mouth once daily, in the morning, at least 1 hour before a meal.
• The recommended treatment length is 9 months.
• When stopping, the dose is reduced to 8 mg once daily for the last 2 weeks of therapy.

What happens if I miss a dose?

Take your next dose at the usual scheduled time. Do not take two doses at one time to make up for a missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Serious harm from a single overdose of a corticosteroid is rare.

• Avoid grapefruit and grapefruit juice, which can raise budesonide levels in the body and increase the risk of side effects.
• Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chickenpox or measles, which can be serious or even fatal in people taking Tarpeyo.

Budesonide is broken down in the body by a liver enzyme called CYP3A4, so medicines and foods that strongly block this enzyme can raise budesonide levels and the risk of side effects. Tell your doctor and pharmacist about all the prescription and over-the-counter medicines, vitamins, and herbal products you take, especially:

• Grapefruit juice
• Antifungal medicines such as ketoconazole and itraconazole
• HIV medicines such as ritonavir, indinavir, and saquinavir
• The antibiotic erythromycin
• Cyclosporine

The use of these potent CYP3A4 blockers with Tarpeyo should be avoided. Medicines that speed up CYP3A4 may lower budesonide levels and make it less effective. This list is not complete, and other drugs may interact with budesonide.

Store Tarpeyo at room temperature, 68°F to 77°F (20°C to 25°C). Brief exposure to temperatures between 59°F and 86°F (15°C and 30°C) is allowed. Keep the container tightly closed and protect the capsules from moisture. Keep this and all medicines out of the reach of children.

Active ingredient: budesonide 4 mg per delayed-release capsule.

Inactive ingredients: sugar spheres (sucrose and starch), hypromellose, polyethylene glycol, citric acid monohydrate, ethyl cellulose, medium chain triglycerides, and oleic acid. The capsule shell contains hypromellose and titanium oxide (E171). The printing ink contains shellac, propylene glycol, and black iron oxide (E172). The enteric coating contains methacrylic acid and methacrylate copolymer, talc, and dibutyl sebacate.