Effective Date

Date of Origin 

10-01-2024            

10-01-2023

Filspari®
(sparsentan)

Tablet

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

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).(4)

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).(4)

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.(4)

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:(4)

• 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.(4)

Efficacy

Filspari (sparsentan) is an endothelin and angiotensin II receptor antagonist. The effect of Filspari on proteinuria was assessed in a randomized, double-blind, active-controlled, multicenter, global study (PROTECT, NCT03762850) in adults with biopsy-proven IgAN, eGFR greater than or equal to 30 mL/min/1.73 m^2, and total urine protein greater than or equal to 1.0 g/day on a maximized stable dose of renin-angiotensin- system (RAS) inhibitor treatment for at least 12 weeks that was at least 50% of maximum labeled dose.(1,2) Patients with other glomerulopathies or those who had been recently treated with systemic immunosuppressants were excluded. Patients were randomized (1:1) to either Filspari (400 mg once daily following 200 mg once daily for 14 days) or irbesartan (300 mg once daily following 150 mg once daily for 14 days). Rescue immunosuppressive treatment could be initiated per investigator discretion during the trial, but use of SGLT2 inhibitors was prohibited. The 281 patients who reached week 36 had a mean (SD) baseline eGFR of 56 (24) mL/min/1.73 m^2. Rescue immunosuppressive treatment was initiated in 1.4% and 5.7% of Filspari and irbesartan patients, respectively. The primary endpoint of the interim analysis was the relative change from baseline in urine protein to creatinine ratio (UPCR) at week 36. The adjusted geometric mean percent change (GMPC) from baseline was -45% in the Filspari arm and -15% in the irbesartan arm, a statistically significant reduction. The ratio of adjusted geometric mean (GM) relative to baseline at week 36 was 0.65 (0.55, 0.77; 95% CI; p less than 0.0001). The treatment effect on UPCR at Week 36 was consistent across subgroups including age, sex, race, and baseline eGFR and proteinuria levels.(1)

Safety

Filspari (sparsentan) has a boxed warning for hepatotoxicity and embryo-fetal toxicity and is available only through a risk evaluation and mitigation strategy (REMS) program (Filspari REMS):(1)

• Elevations in aminotransferases (ALT or AST) of at least 3 times the upper limit of normal (ULN) were observed in up to 2.5% of Filspari treated patients in clinical studies. Transaminases and bilirubin should be measured before initiating treatment, monthly for the first 12 months, and then every 3 months during treatment. Interrupt treatment and closely monitor patients who develop aminotransferase elevations more than 3x ULN. Filspari should be avoided in patients with elevated aminotransferases greater than 3 times ULN at baseline because monitoring for hepatoxicity may be more difficult and these patients may be at increased risk for serious hepatotoxicity.
• Because Filspari can cause major birth defects if used by pregnant patients, pregnancy testing is required before initiation of treatment, during treatment, and one month after discontinuation of treatment with Filspari. Patients who can become pregnant must use effective contraception before the initiation of treatment, during treatment, and for one month after the discontinuation of treatment with Filspari.

Filspari is contraindicated in patients who are pregnant. Filspari is contraindicated to be coadministered with ARBs, endothelin receptor antagonists (ERAs), or aliskiren.(1) 

Prior to initiating treatment with Filspari, discontinue use of renin-angiotensin-aldosterone system (RAAS) inhibitors, ERAs, and aliskiren.(1)

1

Filspari prescribing information. Travere Therapeutics, Inc. February 2023

2

Heerspink HJL, Radhakrishnan J, Alpers CE, et al. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. The Lancet. 2023;401(10388):1584-1594. doi:10.1016/s0140-6736(23)00569-x

3

Reference no longer used.

4

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

5

Reference no longer used.

Filspari

sparsentan tab

200 MG ; 400 MG

M ; N ; O ; Y

N

Filspari

sparsentan tab

200 MG

30

Tablets

30

DAYS

Filspari

sparsentan tab

400 MG

30

Tablets

30

DAYS

Filspari

sparsentan tab

200 MG ; 400 MG

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

Filspari

sparsentan tab

200 MG

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

Filspari

sparsentan tab

400 MG

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

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. ONE of the following:
   1. The patient has a urine protein-to-creatinine ratio (UPCR) greater than or equal to 1.5 g/g OR
   2. The patient has proteinuria greater than or equal to 1 g/day AND
3. The patient’s eGFR is greater than or equal to 30 mL/min/1.73 m^2 AND
4. 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
5. ONE of the following:
   1. The patient has tried and had an inadequate response after at least 3 months 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
   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
6. ONE of the following:
   1. The patient has tried and had an inadequate response after a 6 month course of glucocorticoid therapy (e.g., methylprednisolone, prednisolone, prednisone) OR
   2. The patient has an intolerance or hypersensitivity to a glucocorticoid OR
   3. The patient has an FDA labeled contraindication to ALL glucocorticoids OR
   4. There is support that glucocorticoid therapy is NOT appropriate for the patient AND
7. The patient will NOT use the requested agent in combination with an ACEI, ARB, endothelin receptor antagonist (ERA, e.g., bosentan), or aliskiren AND
8. 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
9. 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.

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

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: 
   1. Decrease from baseline (prior to treatment with the requested agent) of urine protein-to-creatinine (UPCR) ratio OR
   2. Decrease from baseline (prior to treatment with the requested agent) in proteinuria AND
3. The patient will NOT use the requested agent in combination with an angiotensin-converting-enzyme inhibitor (ACEI, e.g., benazepril, lisinopril), angiotensin II blocker (ARB, e.g., losartan), endothelin receptor antagonist (ERA, e.g., bosentan), or aliskiren AND
4. 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
5. 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.

QL with PA

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 12 months