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ph-1216

Rivfloza (nedosiran) Prior Authorization with Quantity Limit Program Summary

Policy Number: PH-1216

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
04-01-2024	04-01-2024

FDA APPROVED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Rivfloza™ (nedosiran) Injection for subcutaneous use	To lower urinary oxalate levels in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function, e.g., eGFR greater than or equal to 30 mL/min/1.73^2		1

Agent(s)

FDA Indication(s)

Notes

Ref#

Rivfloza™

(nedosiran)

Injection for subcutaneous use

To lower urinary oxalate levels in children 9 years of age and older and adults with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function, e.g., eGFR greater than or equal to 30 mL/min/1.73^2

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Primary Hyperoxaluria

The primary hyperoxalurias are rare autosomal recessive inborn errors of metabolism of which three have been described at the molecular level. Primary hyperoxaluria type 1 (PH1) results from mutations in the AGXT gene with associated dysfunction of the vitamin B6 (pyridoxine)-dependent liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT).(3) The disorder results in overproduction and excessive urinary excretion of oxalate, causing recurrent urolithiasis and nephrocalcinosis. As glomerular filtration rate declines due to progressive renal involvement, oxalate accumulates leading to systemic oxalosis.(2) Long-term consequences include cardiomyopathy, cardiac conduction disturbances, vasculopathy, heart block, treatment resistant anemia, oxalate osteopathy resulting in debilitating bone and joint pain, retinopathy and if untreated, early death.(4)

The first sign or symptom is usually blood in the urine, pain, passage of a stone, or urinary tract infection. Patients with renal failure due to “infantile oxalosis” present with failure to thrive, anemia and acidosis. The majority of patients are symptomatic early in life and mostly before 10 years of age.(4)

The usual biochemical indicator of PH1 is a persistently and markedly elevated urine oxalate (UOx) excretion in the absence of secondary causes of hyperoxaluria. Once a raised urinary oxalate has been identified, the diagnosis is confirmed through genetic testing for mutation in the AGXT gene OR liver biopsy indicating deficiency of AGT enzyme activity.(2,3,4) Urinary oxalate measurements may be falsely low in patients with kidney insufficiency and progressive disease, which is common in patients with PH1. In this setting, plasma oxalate levels may be useful to help support the diagnosis of PH1.(5)

Therapy is recommended as soon as a diagnosis of PH1 has been confirmed. High fluid intake is mandatory and may require the placement of a nasogastric or gastrostomy feeding tube. Alkalization of the urine with potassium citrate is recommended to reduce urinary calcium oxalate precipitation thus decreasing stone growth or nephrocalcinosis.(2,3,4) It may be replaced by sodium citrate appropriate to GFR and plasma potassium.(2,4) Pyridoxine (vitamin B6) is a co-factor for AGT and the administration of pyridoxine has been associated with a decrease in urine oxalate in about 30% of PH1 patients. Guidelines recommend that all patients receive administration of pyridoxine for a test period of a minimum of 3 months.(2,3,4) For those patients who are responsive (defined as a greater than 30% decrease in urine oxalate), pyridoxine should be continued indefinitely or until liver transplantation. To date, the only curative treatment for PH1 is combined liver-kidney transplantation.(2,4)

Efficacy

PHYOX2 was a randomized, double-blind trial (NCT03847909) comparing Rivfloza and placebo in patients aged 6 years or older with PH1 or PH2 and an eGFR greater than or equal to 30 mL/min/1.73 m^2. Patients received monthly doses of Rivfloza (n=23) or placebo (n=12). In the patient population, 83% had PH1, and 17% had PH2; 60% were taking pyridoxine.(1) Additional criteria include (but are not limited to): diagnosis must be genetically confirmed, no kidney or liver transplantation (previous or planned).(6)

The primary efficacy endpoint was the area under the curve, from Days 90 to 180, of the percent change from baseline in 24-hour urinary oxalate excretion (AUC-24h-Uox). The least-squares (LS) mean AUC-24h-Uox was -3486 (95% CI: -5025, -1947) in the Rivfloza group compared to 1490 (95% CI: 781, 3761) in the placebo group, for a between group difference of 4976 (95% CI: 2803, 7149; p less than 0.0001). The LS mean percent change from baseline in 24-hour urinary oxalate excretion averaged over Days 90, 120, 150 and 180, was -37% (95% CI: -53%, -21%) in the Rivfloza group and 12% (95% CI: -12%, 36%) in the placebo group, for a between group difference of 49% (95% CI: 26%, 72%). Among patients specifically with PH1, the between group difference was 56% (95% CI: 33%, 80%). After 6 months of treatment in PHYOX2, patients could enroll in an ongoing single-arm extension study, PHYOX3 (NCT04042402), in which all patients were treated with Rivfloza. The reduction in urinary oxalate was maintained in the 13 patients with PH1 who received an additional 6 months of treatment in PHYOX3.(1)

Too few PH2 patients were enrolled to evaluate efficacy in the PH2 population. Therefore, Rivfloza is only indicated for patients with PH1.(1)

Safety

Rivloza (nedosiran) has no boxed warnings or contraindications.(1)

REFERENCES

Number	Reference
1	Rivfloza prescribing information. Novo Nordisk Inc. September 2023.
2	Cochat P, Hulton SA, Acquaviva C, et al. Primary Hyperoxaluria Type 1: Indications for Screening and Guidance for Diagnosis and Treatment. Nephrol Dial Transplant. 2012;27:1729-1736.
3	Hulton SA. The Primary Hyperoxalurias: A Practical Approach to Diagnosis and Treatment. Int J Surg. 2016 Dec;36(D):649-654.
4	Hoppe B, Beck BB, Milliner D. The Primary Hyperoxalurias. Kidney Int. 2009 Jun;75(12):1264-1271.
5	Niaudet P, et al. Primary Hyperoxaluria. UpToDate. Literature review current through September. Last updated August 2023.
6	Baum MA, Langman C, Cochat P, et al. PHYOX2: A Pivotal Randomized Study of Nedosiran in Primary Hyperoxaluria Type 1 or 2. Kidney Int. 2023 Jan;103(1):207-217.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Rivfloza	nedosiran sodium subcutaneous soln ; nedosiran sodium subcutaneous soln pref syr	128 MG/0.8ML ; 160 MG/ML ; 80 MG/0.5ML	M ; N ; O ; Y	N

POLICY AGENT SUMMARY QUANTITY LIMIT

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	QL Amount	Dose Form	Day Supply	Duration	Addtl QL Info	Allowed Exceptions	Targeted NDCs When Exclusions Exist

Rivfloza	nedosiran sodium subcutaneous soln	80 MG/0.5ML	2	Vials	30	DAYS
Rivfloza	nedosiran sodium subcutaneous soln pref syr	128 MG/0.8ML	1	Syringe	30	DAYS
Rivfloza	nedosiran sodium subcutaneous soln pref syr	160 MG/ML	1	Syringe	30	DAYS

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Rivfloza	nedosiran sodium subcutaneous soln ; nedosiran sodium subcutaneous soln pref syr	128 MG/0.8ML ; 160 MG/ML ; 80 MG/0.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

CLIENT SUMMARY – QUANTITY LIMITS

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Rivfloza	nedosiran sodium subcutaneous soln	80 MG/0.5ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Rivfloza	nedosiran sodium subcutaneous soln pref syr	160 MG/ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx
Rivfloza	nedosiran sodium subcutaneous soln pref syr	128 MG/0.8ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Initial Evaluation Target Agent(s) will be approved when ALL of the following are met: The patient has a diagnosis of primary hyperoxaluria type 1 (PH1) confirmed by ONE of the following: Genetic testing of the AGXT gene indicates a pathogenic mutation OR Liver biopsy demonstrates absent or significantly reduced alanine:glyoxylate aminotransferase (AGT) activity AND The requested agent will be used to lower urinary oxalate levels AND The patient has an estimated GFR (eGFR) greater than or equal to 30 mL/min/1.73^2 AND If the patient has an FDA approved indication, then ONE of the following: The patient's age is within FDA labeling for the requested indication for the requested agent OR The prescriber has provided information in support of using the requested agent for the patient's age for the requested indication AND ONE of the following: The patient has tried and had an inadequate response to potassium citrate or sodium citrate OR The patient has an intolerance or hypersensitivity to potassium citrate or sodium citrate therapy OR The patient has an FDA labeled contraindication to BOTH potassium citrate AND sodium citrate AND ONE of the following: The patient has tried and had an inadequate response to pyridoxine (vitamin B6) for at least 3 months AND ONE of the following: The patient is unresponsive to pyridoxine (vitamin B6) (unresponsive defined as less than or equal to 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) OR The patient is responsive to pyridoxine (vitamin B6) (responsive defined as greater than 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) AND will continue treatment with pyridoxine (vitamin B6) in combination with the requested agent OR The patient has an intolerance or hypersensitivity to pyridoxine (vitamin B6) therapy OR The patient has an FDA labeled contraindication to pyridoxine (vitamin B6) AND The patient has not received a kidney or liver transplant AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 6 months 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: The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND The patient has had clinical benefit with the requested agent (e.g., decrease in urinary oxalate levels) AND The patient has an estimated GFR (eGFR) greater than or equal to 30 mL/min/1.73^2 AND ONE of the following: ONE of the following: The patient will continue treatment with pyridoxine (vitamin B6) in combination with the requested agent OR The patient was unresponsive to pyridoxine (vitamin B6) (unresponsive defined as less than or equal to 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) OR The patient has an intolerance or hypersensitivity to pyridoxine (vitamin B6) therapy OR The patient has an FDA labeled contraindication to pyridoxine (vitamin B6) AND The patient has not received a kidney or liver transplant AND The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND The patient does NOT have any FDA labeled contraindications to the requested agent Length of Approval: 12 months

Module

Clinical Criteria for Approval

Initial Evaluation

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

The patient has a diagnosis of primary hyperoxaluria type 1 (PH1) confirmed by ONE of the following:
1. Genetic testing of the AGXT gene indicates a pathogenic mutation OR
2. Liver biopsy demonstrates absent or significantly reduced alanine:glyoxylate aminotransferase (AGT) activity AND
The requested agent will be used to lower urinary oxalate levels AND
The patient has an estimated GFR (eGFR) greater than or equal to 30 mL/min/1.73^2 AND
If the patient has an FDA approved 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. The prescriber has provided information in support of using the requested agent for the patient's age for the requested indication AND
ONE of the following:
1. The patient has tried and had an inadequate response to potassium citrate or sodium citrate OR
2. The patient has an intolerance or hypersensitivity to potassium citrate or sodium citrate therapy OR
3. The patient has an FDA labeled contraindication to BOTH potassium citrate AND sodium citrate AND
ONE of the following:
1. The patient has tried and had an inadequate response to pyridoxine (vitamin B6) for at least 3 months AND ONE of the following:
  1. The patient is unresponsive to pyridoxine (vitamin B6) (unresponsive defined as less than or equal to 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) OR
  2. The patient is responsive to pyridoxine (vitamin B6) (responsive defined as greater than 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) AND will continue treatment with pyridoxine (vitamin B6) in combination with the requested agent OR
2. The patient has an intolerance or hypersensitivity to pyridoxine (vitamin B6) therapy OR
3. The patient has an FDA labeled contraindication to pyridoxine (vitamin B6) AND
The patient has not received a kidney or liver transplant AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 6 months

*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:

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process AND
The patient has had clinical benefit with the requested agent (e.g., decrease in urinary oxalate levels) AND
The patient has an estimated GFR (eGFR) greater than or equal to 30 mL/min/1.73^2 AND
ONE of the following:
1. ONE of the following:
  1. The patient will continue treatment with pyridoxine (vitamin B6) in combination with the requested agent OR
  2. The patient was unresponsive to pyridoxine (vitamin B6) (unresponsive defined as less than or equal to 30% decrease in urine oxalate after 3 months of treatment with maximally tolerated pyridoxine) OR
2. The patient has an intolerance or hypersensitivity to pyridoxine (vitamin B6) therapy OR
3. The patient has an FDA labeled contraindication to pyridoxine (vitamin B6) AND
The patient has not received a kidney or liver transplant AND
The prescriber is a specialist in the area of the patient’s diagnosis (e.g., gastroenterologist, nephrologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval: 12 months

QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL

Module	Clinical Criteria for Approval
	Quantity limit for the Target Agent(s) will be approved when ONE of the following is met: The requested quantity (dose) does NOT exceed the program quantity limit OR ALL of the following: The requested quantity (dose) exceeds the program quantity limit AND The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit Length of Approval: 6 months (Initial); 12 months (Renewal)

Module

Clinical Criteria for Approval

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

The requested quantity (dose) does NOT exceed the program quantity limit OR
ALL of the following:
1. The requested quantity (dose) exceeds the program quantity limit AND
2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit

Length of Approval: 6 months (Initial); 12 months (Renewal)

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.

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