FDA LABELED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Vanrafia® (atrasentan) Tablet |
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) greater than or equal to 1.5 g/g |
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1 |
This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.
PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
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Initial Evaluation 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. If the patient has an FDA labeled indication, then ONE of the following: A. The patient’s age is within FDA labeling for the requested indication for the requested agent OR B. There is support for using the requested agent for the patient’s age for the requested indication AND 3. ONE of the following: A. The patient has a urine protein-to-creatinine ratio (UPCR) greater than or equal to 0.44 g/g OR B. The patient has proteinuria greater than or equal to 0.5 g/day AND 4. The patient’s eGFR is greater than or equal to 30 mL/min/1.73 m^2 AND 5. The patient has ONE of the following: A. Tried and had an inadequate response after at least a 3-month duration of therapy with a maximally tolerated angiotensin-converting-enzyme inhibitor (ACEi, e.g., benazepril, lisinopril) or angiotensin II blocker (ARB, e.g., losartan), or a combination medication containing an ACEi or ARB OR B. An intolerance or hypersensitivity to an ACEi or ARB, or a combination medication containing an ACEi or ARB OR C. An FDA labeled contraindication to ALL ACEi or ARB AND 6. 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 7. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 9 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.
Renewal Evaluation Target Agent(s) will be approved when ALL of the following are met: 1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND 2. The patient has had improvements or stabilization with the requested agent as indicated by ONE of the following: A. Decrease from baseline (prior to treatment with the requested agent) of urine protein-to-creatinine (UPCR) ratio OR B. Decrease from baseline (prior to treatment with the requested agent) in proteinuria AND 3. 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 4. The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
PRIOR AUTHORIZATION CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
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Validation: Apply Baseline and go to Validation Options |
Age Verification;Contraind., intolerance, or hypersensitivity to prereq.;Lab Values;Renewal Clinical Benefit - check for specific efficacy/improvement |
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QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
Universal 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: A. 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 B. BOTH of the following: A. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND B. 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 C. BOTH of the following: A. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND B. There is support for therapy with a higher dose for the requested indication Length of Approval: up to 12 months |
QUANTITY LIMIT CLINICAL CRITERIA OPERATIONAL LEVEL OF EVIDENCE REQUIREMENTS
Module |
Ops Set Up |
Validation Options |
Other Explanation |
Universal QL |
Validation: Apply Baseline and go to Validation Options |
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J8499
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 many years. Eventually, IgAN can lead to end-stage renal disease (ESRD).(2) 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 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).(2) 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.(2) Recent literature also supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a component of maximal supportive care.(2,3) Furthermore, recent guidelines recommend simultaneous commencement of disease-modifying therapy and therapies to manage the consequences of IgAN-induced nephron loss.(2) Guidelines define a patient with IgAN at risk of progressive loss of kidney function if they have a proteinuria greater than or equal to 0.5 g/d (or equivalent).(2) Proteinuria of 0.5 g/d is approximately equivalent to a urine protein to creatinine ratio (UPCR) of 0.44 g/g.(4) Systemic glucocorticoids have no proven impact on levels of pathogenic forms of IgA or IgA immune complexes and are used to manage glomerular inflammation. However, Tarpeyo (Nefecon) is recommended in the 2024 KDIGO guidelines as efficacy data supports a reduction in pathogenic IgA and IgA immune complexes.(2) The American Journal of Kidney Disease (AJKD) recommends corticosteroids (targeted release budesonide, Nefecon, or reduced dose corticosteroids) for high-risk patients with inflammatory lesions seen on kidney biopsy.(3) Most literature supports some use of corticosteroids as part of a treatment regimen however, the dose and duration is questionable.(2,3) Furthermore, long-term outcomes-based comparative studies for corticosteroids in the IgAN setting is lacking and future studies are needed to determine any clinical significance. It is further noted that the following patient characteristics are likely to increase the risks of systemic glucocorticoid toxicity:(2) · eGFR less than 30 mL/min/1.73 m^2 · Diabetes and prediabetes · Obesity · Latent infections (e.g., viral hepatitis, tuberculosis) · Active peptic ulceration · Uncontrolled psychiatric illness · Osteoporosis · Cataracts The goal of treatment in patients with IgAN at risk of progressive loss of kidney function is to reduce the rate of loss of kidney function to less than 1 mL/min per year for the rest of the patient's life. An additional treatment goal is the reduction of proteinuria to less than 0.5 g/d (or equivalent).(2) |
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Efficacy |
Vanrafia is an endothelin type A (ETA) receptor antagonist. The effect of Vanrafia on proteinuria was assessed in a randomized, double-blind, placebo-controlled, multicenter, global study (ALIGN, NCT04573478) in adults with biopsy-proven primary IgAN, an eGFR greater than or equal to 30 mL/min/1.73 m^2, and urine protein greater than or equal to 1 g/day on a stable dose of maximally tolerated renin angiotensin system (RAS) inhibitor for a minimum of 12 weeks. The study included two cohorts: a main cohort of 340 patients and an exploratory cohort of 64 patients who were also on a stable dose of sodium glucose co-transporter 2 inhibitor (SGLT2i) at baseline. Patients with chronic kidney disease due to another condition in addition to IgAN or those who had been recently treated with systemic immunosuppressants were excluded. Patients were randomized (1:1) to receive either Vanrafia 0.75 mg or placebo once daily. RAS inhibitor therapy was continued throughout the study. Rescue immunosuppressive treatment could be initiated per investigator discretion during the trial.(1) The primary endpoint was the percent reduction in UPCR at Week 36 relative to baseline and the results were as follows:(1)
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Safety |
Vanrafia has a boxed warning for embryo-fetal toxicity:(1)
Vanrafia is contraindicated in the following:(1)
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Number |
Reference |
1 |
Vanrafia prescribing information. Novartis Pharmaceuticals Corporation. April 2025. |
2 |
KDIGO 2024 CLINICAL PRACTICE GUIDELINE FOR THE MANAGEMENT OF IMMUNOGLOBULIN A NEPHROPATHY (IgAN) AND IMMUNOGLOBULIN A VASCULITIS (IgAV); 2024. https://kdigo.org/wp-content/uploads/2024/08/KDIGO-2024-IgAN-IgAV-Guideline-Public-Review-Draft.pdf |
3 |
Caster DJ, Lafayette RA. The treatment of primary IGA nephropathy: Change, change, change. American Journal of Kidney Diseases. 2023;83(2):229-240. doi:10.1053/j.ajkd.2023.08.007 |
4 |
Pitcher D, Braddon F, Hendry B, et al. Long-Term outcomes in IGA nephropathy. Clinical Journal of the American Society of Nephrology. 2023;18(6):727-738. doi:10.2215/cjn.0000000000000135 |
POLICY AGENT SUMMARY PRIOR AUTHORIZATION
Final Module |
Target Agent GPI |
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Targeted MSC |
Targeted NDCs When Exclusions Exist |
Final Age Limit |
Preferred Status |
Effective Date |
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564825072003 |
Vanrafia |
atrasentan hcl tab |
0.75 MG |
M ; N ; O ; Y |
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POLICY AGENT SUMMARY QUANTITY LIMIT
Target Agent GPI |
Target Brand Name(s) |
Target Generic Name(s) |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Targeted NDCs When Exclusions Exist |
Age Limit |
Effective Date |
Term Date |
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56482507200320 |
Vanrafia |
atrasentan hcl tab |
0.75 MG |
30 |
Tablets |
30 |
DAYS |
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CLIENT SUMMARY – PRIOR AUTHORIZATION
Target Brand Agent(s) |
Target Generic Agent(s) |
Strength |
Client Formulary |
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Vanrafia |
atrasentan hcl tab |
0.75 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
Target Brand Agent Name(s) |
Target Generic Agent Name(s) |
Strength |
Client Formulary |
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Vanrafia |
atrasentan hcl tab |
0.75 MG |
Commercial ; HIM ; WY NetR-Commercial Custom |
