Description
nedosiran) RIVFLOZA is a new drug that is approved by FDA during 2019 to 2023. 2. Do your research, for example, Drugs@FDA, Journals, CubitAI Video Book on Liquid Formulation, and notes from the courses. (Do not use marketing ads in the presentation. Only science). Presentations Content should be presented in Four Seminars section 7-10 slides each. Must include on slide: Drug Name (Chemical and Brand), Approval Date, Dosage Form(s), and Indication. Please see attachment for Instructions. Attachment is an article, but please use other information from the web.Please add worksite page
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Industrial Pharmacy Specialization Students:
1. (nedosiran) RIVFLOZA is a new drug that is approved by FDA during 2019 to
2023.
2. Do your research, for example, Drugs@FDA, Journals, CubitAI Video Book on
Liquid Formulation, and notes from the courses. (Do not use marketing ads in the
presentation. Only science).
Presentations Content should be presented in Four Seminars section:
Must include on slide: Drug Name (Chemical and Brand), Approval Date, Dosage
Form(s), and Indication. Each seminar must have at least 7-10 Slides
Part 1 Seminar: Pre-Formulation and Physical Chemistry of Rivfloza (7-10 Slides
each)
Part 2 Seminar: Formulation Quantitative Compositions and Functionality of
Excipients of Rivfloza (7-10 Slides)
Part 3 Seminar: Commercial (1000 Kg) Batch Size Manufacturing Process of
Rivfloza (7-10 slides )
Part 4 Seminar: Quality by Design, Pharmacokinetics Studies and Clinical (7-10
slide)
Clinical Policy: Nedosiran (Rivfloza)
Reference Number: CP.PHAR.619
Effective Date: 09.29.23
Last Review Date: 05.23
Line of Business: Commercial, HIM, Medicaid
Coding Implications
Revision Log
See Important Reminder at the end of this policy for important regulatory and legal
information.
Description
Nedosiran (Rivfloza™) is an LDHA-directed small interfering RNA.
FDA Approved Indication(s)
Rivfloza is indicated to lower urinary oxalate (UOx) 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 ≥ 30 mL/min/1.73 m2.
Policy/Criteria
Provider must submit documentation (such as office chart notes, lab results or other clinical
information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Rivfloza is medically
necessary when the following criteria are met:
I. Initial Approval Criteria
A. Primary Hyperoxaluria Type 1 (must meet all):
1. Diagnosis of PH1 confirmed by one of the following (a or b):
a. Genetic testing confirming presence of mutations in the AGXT gene;
b. Liver biopsy confirming AGT enzyme deficiency;
2. Prescribed by or in consultation with an endocrinologist, hepatologist, or
nephrologist;
3. Age ≥ 9 years;
4. Documentation of estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2;
5. Documentation of one of the following (a or b):
a. UOx excretion > 0.70 mmol/1.73 m2/24 h, confirmed on repeat testing;
b. Spot urinary oxalate-to-creatinine (UOx:Cr) molar ratio greater than normal for
age (see Appendix D for reference ranges), confirmed on repeat testing;
6. Failure to achieve normalization of UOx excretion levels after at least three months of
pyridoxine (vitamin B6) at up to maximally indicated doses, unless contraindicated or
clinically significant adverse effects are experienced;
*Normal UOx excretion is < 0.50 mmol (< 45 mg)/1.73 m2/day, or see Appendix D for reference
ranges for age-specific spot UOx:Cr molar ratios.
7. Member has not had a liver transplant;
8. Documentation of member’s current body weight (in kg);
9. Dose does not exceed any of the following, based on age and/or body weight (a, b, or
c):
a. Weight ≥ 50 kg, both of the following (i and ii):
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CLINICAL POLICY
Nedosiran
i. 160 mg per month;
ii. 1 prefilled syringe per month;
b. Age ≥ 12 years and < 50 kg, both of the following (i and ii):
i. 128 mg per month;
ii. 1 prefilled syringe per month;
c. Age 9-11 years and < 50 kg: 3.3 mg/kg, not to exceed 128 mg, per month.
Approval duration: 6 months
B. Other diagnoses/indications (must meet 1 or 2):
1. If this drug has recently (within the last 6 months) undergone a label change (e.g.,
newly approved indication, age expansion, new dosing regimen) that is not yet
reflected in this policy, refer to one of the following policies (a or b):
a. For drugs on the formulary (commercial, health insurance marketplace) or PDL
(Medicaid), the no coverage criteria policy for the relevant line of business:
CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and
CP.PMN.255 for Medicaid; or
b. For drugs NOT on the formulary (commercial, health insurance marketplace) or
PDL (Medicaid), the non-formulary policy for the relevant line of business:
CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and
CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed
under section III (Diagnoses/Indications for which coverage is NOT authorized) AND
criterion 1 above does not apply, refer to the off-label use policy for the relevant line
of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance
marketplace, and CP.PMN.53 for Medicaid.
II. Continued Therapy
A. Primary Hyperoxaluria Type 1 (must meet all):
1. Member meets one of the following (a or b):
a. Currently receiving medication via Centene benefit or member has previously met
initial approval criteria;
b. Member is currently receiving medication and is enrolled in a state and product
with continuity of care regulations (refer to state specific addendums for
CC.PHARM.03A and CC.PHARM.03B);
2. Member is responding positively to therapy as evidenced by, including but not
limited to, improvement in either of the following parameters (a or b):
a. Decrease from baseline in UOx excretion of > 30%;
b. Improvement in PH1 symptoms (e.g., nephrolithiasis, nephrocalcinosis, kidney
function, ischemic skin ulcers, metabolic bone disease, refractory anemia,
cardiomyopathy, abnormalities in cardiac conduction) and one of the following (i
or ii):
i. Decrease from baseline in UOx excretion;
ii. Improvement in spot UOx:Cr molar ratio;
3. Member has not had a liver transplant;
4. Documentation of member’s current body weight (in kg);
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CLINICAL POLICY
Nedosiran
5. If request is for a dose increase, new dose does not exceed any of the following, based
on age and/or body weight (a, b, or c):
a. Weight ≥ 50 kg, both of the following (i and ii):
i. 160 mg per month;
ii. 1 prefilled syringe per month;
b. Age ≥ 12 years and < 50 kg, both of the following (i and ii):
i. 128 mg per month;
ii. 1 prefilled syringe per month;
c. Age 9-11 years and < 50 kg: 3.3 mg/kg, not to exceed 128 mg, per month.
Approval duration: 12 months
B. Other diagnoses/indications (must meet 1 or 2):
1. If this drug has recently (within the last 6 months) undergone a label change (e.g.,
newly approved indication, age expansion, new dosing regimen) that is not yet
reflected in this policy, refer to one of the following policies (a or b):
a. For drugs on the formulary (commercial, health insurance marketplace) or PDL
(Medicaid), the no coverage criteria policy for the relevant line of business:
CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and
CP.PMN.255 for Medicaid; or
b. For drugs NOT on the formulary (commercial, health insurance marketplace) or
PDL (Medicaid), the non-formulary policy for the relevant line of business:
CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and
CP.PMN.16 for Medicaid; or
2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed
under section III (Diagnoses/Indications for which coverage is NOT authorized) AND
criterion 1 above does not apply, refer to the off-label use policy for the relevant line
of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance
marketplace, and CP.PMN.53 for Medicaid.
III. Diagnoses/Indications for which coverage is NOT authorized:
A. Non-FDA approved indications, which are not addressed in this policy, unless there is
sufficient documentation of efficacy and safety according to the off label use policies –
CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and
CP.PMN.53 for Medicaid or evidence of coverage documents.
IV. Appendices/General Information
Appendix A: Abbreviation/Acronym Key
AGT: alanine glyoxylate
aminotransferase
FDA: Food and Drug Administration
LDHA: lactate dehydrogenase A
PH1: primary hyperoxaluria type 1
UOx: urinary oxalate
UOx:Cr: urinary oxalate-to-creatinine
Appendix B: Therapeutic Alternatives
This table provides a listing of preferred alternative therapy recommended in the approval
criteria. The drugs listed here may not be a formulary agent for all relevant lines of business
and may require prior authorization.
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CLINICAL POLICY
Nedosiran
Drug Name
Dosing Regimen
pyridoxine
5-20 mg/kg PO QD
Dose Limit/
Maximum Dose
20 mg/kg/day
Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only
and generic (Brand name®) when the drug is available by both brand and generic.
Appendix C: Contraindications/Boxed Warnings
None reported
Appendix D: Spot UOx/Cr Molar Ratio Reference Ranges in Spot Urine Samples
Age
Normal Values
0-6 months
< 325-360 mmol/mol (< 253-282 mg/g)
7-24 months
< 132-174 mmol/mol (< 103-136 mg/g)
2-5 years
< 98-101 mmol/mol (< 76-79 mg/g)
5-14 years
< 70-82 mmol/mol (< 55-64 mg/g)
> 16 years
< 40 mmol/mol (< 32 mg/g)
V. Dosage and Administration
Indication Dosing Regimen
PH1
Adults and adolescents ≥ 12 years of age
Body weight ≥ 50 kg: 160 mg once monthly
Body weight < 50 kg: 128 mg once monthly
Maximum Dose
See dosing
regimen
Children 9 to 11 years
Body weight ≥ 50 kg: 160 mg once monthly
Body weight < 50 kg: 3.3 mg/kg once monthly, not to
exceed 128 mg, and the vial dose volume rounded to the
nearest 0.1 mL
VI. Product Availability
Single-dose vial: 80 mg (0.5 mL)
Single-dose prefilled syringes: 128 mg (0.8 mL), 160 mg (1 mL)
VII. References
1. Rivfloza Prescribing Information. Plainsboro, NJ: Novo Nordisk; September 2023. Available
at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215842s000lbl.pdf. Accessed
October 2, 2023.
2. 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.Available at:
https://www.kidney-international.org/article/S0085-2538(22)00631-7/fulltext. Accessed
October 2, 2023.
3. Milliner DS, Harris PC, Sas DJ, et al. Primary hyperoxaluria type 1. 2002 Jun 19 [Updated
2022 February 10]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®
[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available at:
https://www.ncbi.nlm.nih.gov/books/NBK1283/pdf/Bookshelf_NBK1283.pdf. Accessed
February 16, 2023.
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CLINICAL POLICY
Nedosiran
Coding Implications
Codes referenced in this clinical policy are for informational purposes only. Inclusion or
exclusion of any codes does not guarantee coverage. Providers should reference the most up-todate sources of professional coding guidance prior to the submission of claims for
reimbursement of covered services.
HCPCS Description
Codes
Pending Pending
Reviews, Revisions, and Approvals
Date
Policy created pre-emptively
RT4: Drug is now FDA approved – criteria updated per FDA
labeling: minimum age revised from 6 to ≥ 9 years and maximum
dosing updated per Prescribing Information; references reviewed
and updated.
02.28.23
10.10.23
P&T
Approval
Date
05.23
Important Reminder
This clinical policy has been developed by appropriately experienced and licensed health care
professionals based on a review and consideration of currently available generally accepted
standards of medical practice; peer-reviewed medical literature; government agency/program
approval status; evidence-based guidelines and positions of leading national health professional
organizations; views of physicians practicing in relevant clinical areas affected by this clinical
policy; and other available clinical information. The Health Plan makes no representations and
accepts no liability with respect to the content of any external information used or relied upon in
developing this clinical policy. This clinical policy is consistent with standards of medical
practice current at the time that this clinical policy was approved. “Health Plan” means a health
plan that has adopted this clinical policy and that is operated or administered, in whole or in part,
by Centene Management Company, LLC, or any of such health plan’s affiliates, as applicable.
The purpose of this clinical policy is to provide a guide to medical necessity, which is a
component of the guidelines used to assist in making coverage decisions and administering
benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage
decisions and the administration of benefits are subject to all terms, conditions, exclusions and
limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy,
contract of insurance, etc.), as well as to state and federal requirements and applicable Health
Plan-level administrative policies and procedures.
This clinical policy is effective as of the date determined by the Health Plan. The date of posting
may not be the effective date of this clinical policy. This clinical policy may be subject to
applicable legal and regulatory requirements relating to provider notification. If there is a
discrepancy between the effective date of this clinical policy and any applicable legal or
regulatory requirement, the requirements of law and regulation shall govern. The Health Plan
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CLINICAL POLICY
Nedosiran
retains the right to change, amend or withdraw this clinical policy, and additional clinical
policies may be developed and adopted as needed, at any time.
This clinical policy does not constitute medical advice, medical treatment or medical care. It is
not intended to dictate to providers how to practice medicine. Providers are expected to exercise
professional medical judgment in providing the most appropriate care, and are solely responsible
for the medical advice and treatment of members. This clinical policy is not intended to
recommend treatment for members. Members should consult with their treating physician in
connection with diagnosis and treatment decisions.
Providers referred to in this clinical policy are independent contractors who exercise independent
judgment and over whom the Health Plan has no control or right of control. Providers are not
agents or employees of the Health Plan.
This clinical policy is the property of the Health Plan. Unauthorized copying, use, and
distribution of this clinical policy or any information contained herein are strictly prohibited.
Providers, members and their representatives are bound to the terms and conditions expressed
herein through the terms of their contracts. Where no such contract exists, providers, members
and their representatives agree to be bound by such terms and conditions by providing services to
members and/or submitting claims for payment for such services.
Note:
For Medicaid members, when state Medicaid coverage provisions conflict with the coverage
provisions in this clinical policy, state Medicaid coverage provisions take precedence. Please
refer to the state Medicaid manual for any coverage provisions pertaining to this clinical policy.
©2023 Centene Corporation. All rights reserved. All materials are exclusively owned by
Centene Corporation and are protected by United States copyright law and international
copyright law. No part of this publication may be reproduced, copied, modified, distributed,
displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise
published without the prior written permission of Centene Corporation. You may not alter or
remove any trademark, copyright or other notice contained herein. Centene® and Centene
Corporation® are registered trademarks exclusively owned by Centene Corporation.
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