Effective Date

Date of Origin   

10-01-2024           

05-19-2022

Tarpeyo®

(budesonide)

Delayed release capsule

Reduce the loss of kidney function in adults with primary immunoglobulin A nephropathy (IgAN) who are at risk for disease progression

1

Immunoglobulin A Nephropathy

Immunoglobulin A nephropathy (IgAN), also known as Berger’s disease, is a kidney disease that occurs when IgA deposits build up in the kidneys, causing inflammation that damages the glomeruli, in turn causing the kidneys to leak blood and protein into the urine. The damage may lead to scarring of the nephrons that progresses slowly over may years. Eventually, IgAN can lead to end-stage renal disease (ESRD).(3)

Kidney biopsy is required to confirm the diagnosis of IgAN as there are no validated diagnostic serum or urine biomarkers for IgAN. Biopsy is indicated when a patient has signs of a severe or progressive disease. After a diagnosis has been established, guidelines recommend that all patients with IgAN be assessed for secondary causes (e.g., liver cirrhosis, HIV, hepatitis, inflammatory bowel disease).(3)

The primary focus of IgAN management should be optimized supportive care [e.g., blood pressure management, maximally tolerated angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin II blocker (ARB), lifestyle modification, address cardiovascular risk]. Guidelines recommend that all patients with proteinuria greater than 0.5 g/d be treated with an ACEI or ARB irrespective of whether they have hypertension.(3)

Guidelines define high risk of progression in IgAN as proteinuria greater than 0.75–1 g/d despite at least 90 days of optimized supportive care. It is suggested that patients who remain at high risk despite maximal supportive care be considered for a 6 month course of glucocorticoid therapy. They stress the importance of discussing treatment-emergent toxicity, particularly those who have an estimated glomerular filtration rate (eGFR) less than 50 mL/min/1.73 m^2. It is further noted that glucocorticoids should be given with extreme caution or avoided entirely in the following situations:(3)

• eGFR less than 30 mL/min/1.73 m^2
• Diabetes
• Obesity (BMI greater than 30 kg/m^2)
• Latent infections (e.g., viral hepatitis, tuberculosis)
• Secondary disease (e.g., cirrhosis)
• Active peptic ulceration
• Uncontrolled psychiatric illness
• Severe osteoporosis

The goal of treatment for these patients that remain at high risk for progressive disease is a reduction of proteinuria to less than 1 g/d.(3)

Efficacy

The effect of Tarpeyo on proteinuria and kidney function was assessed in a randomized, double-blind, phase 3, 2-part, multicenter study (NefIgArd, NCT: 03643965) in adult patients (n=364) with biopsy-proven IgAN, eGFR greater than or equal to 35 mL/min/1.73 m^2 , and proteinuria (defined as either greater than or equal to 1 g/day or urine protein to creatinine ratio (UPCR) greater than or equal to 0.8 g/g) who were on a stable dose of maximally-tolerated renin-angiotensin-system (RAS) inhibitor therapy. Patients with other glomerulopathies, nephrotic syndrome, or those who had been treated with systemic immunosuppressive medications were excluded. Patients were randomized 1:1 to either Tarpeyo 16 mg once daily or placebo and treated for 9 months followed by a 2-week taper of either Tarpeyo 8 mg once daily or placebo. Patients were then observed for 15 months, during which no study drug was administered. At baseline, the mean eGFR was approximately 58 mL/min/1.73 m^2 and the mean UPCR was 1.5 g/g. The median age was 43 years (range from 20-73 years). At baseline, 98% of patients were treated with an ACEI or ARB.(1,2)

The primary outcome for Part A of the study was the ratio (reduction) of UPCR (based on 24-hour urine collections) at 9 months compared to baseline. An interim analysis was based on the first 199 randomized patients who completed the Month 9 visit. A 31% reduction in UPCR was seen in patients treated with Tarpeyo 16mg daily compared to a 5% reduction in the placebo group (95% CI: 16% to 42% reduction; p=0.0001). The final analysis of all 364 patients was consistent with the results of the interim analysis.(1,2)

The primary outcome for Part B of the study was a time-weighted average of the log ratio of eGFR at each time point over 2 years relative to baseline to assess the effect of Tarpeyo on long-term kidney function. After 2 years there was a 5.9 mL/min/1.73 m^2 difference in mean change from baseline in eGFR (95% CI: 3.3 to 8.5 mL/min/1.73 m^2; p less than 0.0001). This treatment effect at 2 years was consistent across key subgroups, including baseline disease characteristics (e.g., baseline proteinuria).(1)

Safety

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.(1)

1

Tarpeyo prescribing information. Calliditas Therapeutics AB. December 2023.

2

Barratt J, Lafayette RA, Kristensen JK, et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin A nephropathy. Kidney International. 2023;103(2):391-402. doi:10.1016/j.kint.2022.09.017

3

Rovin BH, Adler SG, Barratt J, et al. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney International. 2021;100(4):S1-S276. doi:10.1016/j.kint.2021.05.021

4

Reference no longer used.

Tarpeyo

budesonide delayed release cap

4 MG

M ; N ; O ; Y

N

Tarpeyo

Budesonide Delayed Release Cap

4 MG

120

Capsules

30

DAYS

Tarpeyo

budesonide delayed release cap

4 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tarpeyo

Budesonide Delayed Release Cap

4 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PA

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has a diagnosis of primary immunoglobulin A nephropathy (IgAN) confirmed by kidney biopsy AND
2. The requested agent will be used to reduce the loss of kidney function in a patient at risk for disease progression AND
3. ONE of the following:
   1. The patient has a urine protein-to-creatinine ratio (UPCR) greater than or equal to 0.8 g/g OR
   2. The patient has proteinuria greater than or equal to 1 g/day AND
4. The patient’s eGFR is greater than or equal to 30 mL/min/1.73 m^2 AND
5. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
6. ONE of the following:
   1. BOTH of the following:
      1. The patient has tried and had an inadequate response after at least 3 months of therapy with maximally tolerated ACEI or ARB (e.g., benazepril, lisinopril, losartan), or a combination medication containing an ACEI or ARB AND
      2. The patient will be using an ACEI or ARB or a combination medication containing an ACEI or ARB in combination with the requested agent OR
   2. The patient has an intolerance or hypersensitivity to an ACEI or ARB, or a combination medication containing an ACEI or ARB OR
   3. The patient has an FDA labeled contraindication to ALL ACEI or ARB AND
7. ONE of the following:
   1. The patient has an intolerance or hypersensitivity to oral generic budesonide that is not expected to occur with the requested agent OR
   2. The patient has an FDA labeled contraindication to oral generic budesonide that is not expected to occur with the requested agent AND
8. ONE of the following:
   1. The patient has not previously been treated with a course of therapy (9 months) with the requested agent OR
   2. The patient has previously been treated with a course of therapy with the requested agent, AND there is support for an additional course of therapy with the requested agent AND
9. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
10. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 10 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit criteria. 

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

QL

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR  
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. ​​​​​​​The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

​​​​​​​​​​​​​​Length of Approval: up to 10 months