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Indication

TARPEYO® (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) 1.5 g/g.

This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

Important Safety Information

Contraindications:

TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations.

Warnings and Precautions

Hypercorticism and adrenal axis suppression:

When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression.

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B).

Risks of immunosuppression:

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg, chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines.

Other corticosteroid effects:

TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects.

Adverse reactions:

In clinical studies, the most common adverse reactions with TARPEYO (occurring in 5% of TARPEYO patients and 2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weight increase (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%).

Drug interactions:

Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide.

Use in specific populations

Pregnancy:

The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism.

Please see Full Prescribing Information.

References: 1. TARPEYO. Prescribing Information. Calliditas Therapeutics AB; 2021. 2. Barratt J, Rovin BH, Cattran D, et al. Why target the gut to treat IgA nephropathy? Kidney Int Rep. 2020;5(10):1620-1624. doi:10.1016/j.ekir.2020.08.009 3. Data on file. Calliditas Therapeutics AB. 4. Fellström BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017;389(10084):2117-2127. doi:10.1016/S0140-6736(17)30550-0 5. Kiryluk K, Novak J. The genetics and immunobiology of IgA nephropathy. J Clin Invest. 2014;124(6):2325-2332. doi:10.1172/JCI74475 6. Wehbi B, Oblet C, Boyer F, et al. Mesangial deposition can strongly involve innate-like IgA molecules lacking affinity maturation. J Am Soc Nephrol. 2019;30(7):1238-1249. doi:10.1681/ASN.2018111089 7. Cheung CK, Barratt J. Pathogenesis of IgA nephropathy. UpToDate. Accessed April 5, 2022. https://www.uptodate.com/contents/pathogenesis-of-iga-nephropathy. 8. Bhachu JS, Scionti K, Muto M, Molyneux K, Barratt J. Targeted release-budesonide (Nefecon) modifies circulating IgA-IgGimmune complex levels and levels of poorly O-galactosylated IgA in IgAN [abstract 0038]. Kidney Dis. 2018;4(3):121-122. 9. KDIGO Clinical Practice Guideline for Glomerulonephritis. June 2012. Accessed April 5, 2022. https://kdigo.org/wp-content/uploads/2017/02/KDIGO-2012-GN-Guideline-English.pdf. 10. Hall YN, Fuentes EF, Chertow GM, Olson JL. Race/ethnicity and disease severity in IgA nephropathy. BMC Nephrol. 2004;5:10.
doi:10.1186/1471-2369-5-10 11. Trachtman H, Nelson P, Adler S, et al; for DUET Study Group. DUET: a phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS. J Am Soc Nephrol. 2018;29(11):2745-2754. doi: 10.1681/ASN.2018010091 12. Barratt J, Tumlin JA, Suzuki Y, et al. 24-week interim analysis of a randomized, double-blind, placebo-controlled phase 2 study of atacicept in patients with IgA nephropathy and persistent proteinuria. Abstract presented at: American Society of Nephrology Kidney Week; October 20-25, 2020; Denver, CO. 13. Thompson A, Carroll K, Inker LA, et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol. 2019;14(3):469-481. doi:10.2215/CJN.08600718 14. Barratt J, Feehally J. Primary IgA nephropathy: new insights into pathogenesis. Semin Nephrol.
2011;31(4):349-360. doi:10.1016/j.semnephrol.2011.06.006 15. de Sousa-Pereira P, Woof JM. IgA: structure, function, and developability. Antibodies (Basel). 2019;8(4):57. doi:10.3390/antib8040057

TARPEYO: Proven reduction in UPCR at 9 months1

Patients treated with TARPEYO plus RASi achieved ≥6x UPCR reductions vs RASi alone at 9 months1

upcr
  • 31% reduction (95% CI, 16-42) in UPCR with TARPEYO plus RASi vs RASi alone at 9 months (P=0.0001)1*†‡

Regardless of eGFR and proteinuria at baseline, UPCR reductions were broadly consistent and favored TARPEYO1,3§

*All patients with a UPCR reading regardless of use of prohibited medication at 9 months.1,3

Adjusted geometric least squares mean ratio of UPCR relative to baseline were based on a longitudinal repeated measures model.   1

The estimate of the ratio of geometric mean ratio of UPCR relative to baseline comparing TARPEYO 16 mg plus RASi with RASi alone was reported as percentage reduction along with the respective 95% confidence interval from the longitudinal repeated measures model and P  values. 1

§This study was not powered to show statistical significance across these subgroups. 3

UPCR reductions over time1,3

upcr

At the 12-month observational follow-up, a 53% reduction in UPCR from baseline was reported with TARPEYO plus RASi vs 9% with RASi alone3*§||

  • In a post hoc subgroup analysis of patients with baseline UPCR ≥1.5 g/gram:
    • 43% reduction in UPCR from baseline with TARPEYO plus RASi (n=35) vs 1% with RASi alone (n=38) at 9 months
    • 54% reduction in UPCR from baseline with TARPEYO plus RASi (n=35) vs 13% with RASi alone (n=38) at 12 months

Additional data presented prior to or beyond the primary endpoint of 9 months or from subgroup analyses should be interpreted cautiously.

*All patients with a UPCR reading regardless of use of prohibited medication.1

Adjusted geometric least squares mean ratio of UPCR relative to baseline were based on a longitudinal repeated measures model.1

The estimate of the ratio of geometric mean ratio of UPCR relative to baseline comparing TARPEYO 16 mg plus RASi with RASi alone was reported as percentage reduction along with the respective 95% confidence interval from the longitudinal repeated measures model and P  values.1

§Full analysis set (TARPEYO=97, placebo=102). Not all patients in the full analysis set contributed data at each postbaseline time point, including at 12 months.3

||49% reduction (95% CI, 37-58) in UPCR with TARPEYO plus RASi vs RASi alone.3#

This study was not powered to show statistical significance across these subgroups.3

#The estimate of the ratio of geometric mean ratio of UPCR relative to baseline comparing TARPEYO 16 mg plus RASi with RASi alone was reported as percentage reduction along with the respective 95% confidence interval from the longitudinal repeated measures model.  1

Indication

TARPEYO® (budesonide) delayed release capsules is a corticosteroid indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression, generally a urine protein-to-creatinine ratio (UPCR) 1.5 g/g.

This indication is approved under accelerated approval based on a reduction in proteinuria. It has not been established whether TARPEYO slows kidney function decline in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

Important Safety Information

Contraindications:

TARPEYO is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of TARPEYO. Serious hypersensitivity reactions, including anaphylaxis, have occurred with other budesonide formulations.

Warnings and Precautions

Hypercorticism and adrenal axis suppression:

When corticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Corticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. When discontinuing therapy [see Dosing and Administration] or switching between corticosteroids, monitor for signs of adrenal axis suppression.

Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to oral budesonide. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism in patients with moderate hepatic impairment (Child-Pugh Class B).

Risks of immunosuppression:

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressive doses of corticosteroids. Avoid corticosteroid therapy in patients with active or quiescent tuberculosis infection; untreated fungal, bacterial, systemic viral, or parasitic infections; or ocular herpes simplex. Avoid exposure to active, easily transmitted infections (eg, chicken pox, measles). Corticosteroid therapy may decrease the immune response to some vaccines.

Other corticosteroid effects:

TARPEYO is a systemically available corticosteroid and is expected to cause related adverse reactions. Monitor patients with hypertension, prediabetes, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataracts, a family history of diabetes or glaucoma, or with any other condition in which corticosteroids may have unwanted effects.

Adverse reactions:

In clinical studies, the most common adverse reactions with TARPEYO (occurring in 5% of TARPEYO patients and 2% higher than placebo) were hypertension (16%), peripheral edema (14%), muscle spasms (13%), acne (11%), dermatitis (7%), weight increase (7%), dyspnea (6%), face edema (6%), dyspepsia (5%), fatigue (5%), and hirsutism (5%).

Drug interactions:

Budesonide is a substrate for CYP3A4. Avoid use with potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine. Avoid ingestion of grapefruit juice with TARPEYO. Intake of grapefruit juice, which inhibits CYP3A4 activity, can increase the systemic exposure to budesonide.

Use in specific populations

Pregnancy:

The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with IgAN. Infants exposed to in utero corticosteroids, including budesonide, are at risk for hypoadrenalism.

Please see Full Prescribing Information.

References: 1. TARPEYO. Prescribing Information. Calliditas Therapeutics AB; 2021. 2. Barratt J, Rovin BH, Cattran D, et al. Why target the gut to treat IgA nephropathy? Kidney Int Rep. 2020;5(10):1620-1624. doi:10.1016/j.ekir.2020.08.009 3. Data on file. Calliditas Therapeutics AB. 4. Fellström BC, Barratt J, Cook H, et al. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017;389(10084):2117-2127. doi:10.1016/S0140-6736(17)30550-0 5. Kiryluk K, Novak J. The genetics and immunobiology of IgA nephropathy. J Clin Invest. 2014;124(6):2325-2332. doi:10.1172/JCI74475 6. Wehbi B, Oblet C, Boyer F, et al. Mesangial deposition can strongly involve innate-like IgA molecules lacking affinity maturation. J Am Soc Nephrol. 2019;30(7):1238-1249. doi:10.1681/ASN.2018111089 7. Cheung CK, Barratt J. Pathogenesis of IgA nephropathy. UpToDate. Accessed April 5, 2022. https://www.uptodate.com/contents/pathogenesis-of-iga-nephropathy. 8. Bhachu JS, Scionti K, Muto M, Molyneux K, Barratt J. Targeted release-budesonide (Nefecon) modifies circulating IgA-IgG immune complex levels and levels of poorly O-galactosylated IgA in IgAN [abstract 0038]. Kidney Dis. 2018;4(3):121-122. 9. KDIGO Clinical Practice Guideline for Glomerulonephritis. June 2012. Accessed April 5, 2022. https://kdigo.org/wp-content/uploads/2017/02/KDIGO-2012-GN-Guideline-English.pdf. 10. Hall YN, Fuentes EF, Chertow GM, Olson JL. Race/ethnicity and disease severity in IgA nephropathy. BMC Nephrol. 2004;5:10.
doi:10.1186/1471-2369-5-10 11. Trachtman H, Nelson P, Adler S, et al; for DUET Study Group. DUET: a phase 2 study evaluating the efficacy and safety of sparsentan in patients with FSGS. J Am Soc Nephrol. 2018;29(11):2745-2754. doi: 10.1681/ASN.2018010091 12. Barratt J, Tumlin JA, Suzuki Y, et al. 24-week interim analysis of a randomized, double-blind, placebo-controlled phase 2 study of atacicept in patients with IgA nephropathy and persistent proteinuria. Abstract presented at: American Society of Nephrology Kidney Week; October 20-25, 2020; Denver, CO. 13. Thompson A, Carroll K, Inker LA, et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol. 2019;14(3):469-481. doi:10.2215/CJN.08600718 14. Barratt J, Feehally J. Primary IgA nephropathy: new insights into pathogenesis. Semin Nephrol.
2011;31(4):349-360. doi:10.1016/j.semnephrol.2011.06.006 15. de Sousa-Pereira P, Woof JM. IgA: structure, function, and developability. Antibodies (Basel). 2019;8(4):57. doi:10.3390/antib8040057