E-Mail Us Close
Please note that this email should only be used for feedback and comments specifically related to this particular medical policy.
  
Horizon BCBSNJ
Uniform Medical Policy ManualSection:Drugs
Policy Number:199
Effective Date: 05/15/2020
Original Policy Date:12/17/2019
Last Review Date:04/14/2020
Date Published to Web: 12/18/2019
Subject:
Givosiran (Givlaari)

Description:
_______________________________________________________________________________________

IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.

__________________________________________________________________________________________________________________________

Acute hepatic porphyria (AHP), caused by gene mutations, has four distinct subtypes. All are due to missing or deformed genes that produce enzymes involved in the production of heme. Because particles generated in the process of making heme cannot be cleared by patients who have AHP, toxins that build up in the liver cause unpredictable episodes of pain and other symptoms. Attacks may be associated with triggers, such as certain drugs, smoking or stress; but many have no identifiable cause. Not all patients have frequent episodes, however, and some cases are milder than others. In the United States, about one person in 25,000 is believed to have some form of porphyria – equaling around 13,000 patients. Porphyria affects all ethnic groups and all ages. Majority of patients that have AHP will experience symptoms between the ages of 18-45. AHP is more likely to manifest in women than in men however symptoms/attacks tend to decrease when women are nearing the age of menopause. Currently, treatments for AHP address only the symptoms/attacks, not the causes of the condition (prophylaxis). They include antihypertensives, pain relievers and infusions of hemin (an enzyme inhibitor) for acute attacks.

Givlaari (givosiran) is indicated for the treatment of adult patients with acute hepatic porphyria (AHP), a genetic disorder resulting in the buildup of toxic porphyrin molecules which are formed during the production of heme (which helps bind oxygen in the blood). Patients who have the condition are missing or have defects in some of the liver enzymes important in eliminating byproducts of making heme, the iron-rich part of blood that moves oxygen around the body. As a result of the toxins (porphyrins) that accumulate, patients who have AHP experience sudden attacks that often involve intense pain; that may last for several days or weeks; and that can lead to hypertension, neurologic damage, respiratory failure, seizures and even death. Givlaari (givosiran) is a small interfering RNA (siRNA) molecule that reduces the levels of aminolevulinic acid synthase 1 (ALAS1) to decrease the toxins.

On November 20, 2019, The U.S. Food and Drug Administration (FDA) approved Alnylam Pharmaceutical's drug Givlaari (givosiran) subcutaneous injection. The FDA also designated Givlaari (givosiran) as an Orphan Drug, under both Breakthrough Therapy and Priority Review programs. Approval was based on positive results from the ENVISION Phase 3 study, a randomized, double-blind, placebo-controlled, multinational study of 94 patients with AHP, at 36 study sites in 18 countries – the largest interventional study conducted in AHP. In ENVISION, AHP patients on Givlaari (givosiran) experienced 70% (95% CI: 60%, 80%) fewer porphyria attacks compared to placebo over 6 months. Givlaari (givosiran) also resulted in a similar reduction in intravenous hemin use, as well as reductions in urinary aminolevulinic acid (ALA), and urinary porphobilinogen (PBG). Treated patients had less need for hemin infusions, emergency room services and hospitalizations, as well.

In the pivotal ENVISION study, the most common adverse reactions (reported in at least 20% of patients) with Givlaari (givosiran) were nausea (27%) and injection site reactions (25%). Other adverse reactions seen in patients treated with Givlaari (givosiran) (occurring over 5% more frequently than placebo) include rash, serum creatinine increase, transaminase elevations and fatigue. There are warnings for anaphylactic reaction, hepatic toxicity, renal toxicity, and injection site reactions.

The recommended dosing for Givlaari (givosiran) is 2.5mg/kg given subcutaneously (SC) once every month by a healthcare provider. Injections should be administered in a facility that is equipped and staffed to handle any anaphylactic reactions that may occur.


Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance.)


    I. Prior to initiation of Givlaari (givosiran), members must meet ALL of the following criteria:
          • Member must not be pregnant
          • No anticipated liver transplantation
          • No active HIV, hepatitis C virus, or hepatitis B virus infection(s)
          • No history of recurrent pancreatitis
          • The prescriber is a specialist in the area of the patient’s diagnosis (e.g. hepatologist, hematologist, neurologist) or has consulted with a specialist in the area of the patient’s diagnosis
    II. Givlaari (givosiran) is considered medically necessary for adult members with a diagnosis of Acute Hepatic Porphyria (Acute Intermittent Porphyria, Hereditary Corproporhyria, Variegate Porphyria, ALA dehydratase deficient porphyria) when ALL of the following criteria are met:
          A. Member has elevated urinary or plasma PBG (urinary porphobilinogen) or ALA (urinary aminolevulinic acid) values within the past year; AND
          B. Member has active disease, with at least 2 documented porphyria attacks (requiring hospitalization, urgent healthcare visit, or intravenous hemin administration at home) within the last 6 months; AND
          C. Member is not prophylactically using hemin while on the requested treatment (this does NOT include hemin treatment for acute attacks)
    III. When Givlaari (givosiran) is medically necessary for indications as mentioned above, it is covered once a month for 6 months at the following FDA approved dose:
          • 2.5 mg/kg administered by a healthcare professional via subcutaneous injection once monthly
          [INFORMATIONAL NOTE: As per the FDA labeled package insert dosing section: Dosing is based on actual body weight.

          Missed dose: Administer Givlaari (givosiran) as soon as possible after a missed dose. Resume dosing at monthly intervals following administration of the missed dose.

          Dose Modification for Adverse Reactions: Laboratory testing should be conducted monthly in the first 6 months of treatment to look for elevated transaminase levels which can indicate hepatic toxicity. In patients with severe or clinically significant transaminase elevations, who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. In patients who resume dosing at 1.25 mg/kg once monthly without recurrence of severe or clinically significant transaminase elevations, the dose may be increased to the recommended dose of 2.5 mg/kg once monthly.]
    IV. Continued Givlaari (givosiran) is subject to medical necessity review and will be approved annually if the following continuation criteria are met:
          A. Member continues to meet the criteria in section I; AND
          B. Member has a positive response, defined as ≥ 70% reduction from baseline in fewer porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home; AND
          C. No unacceptable toxicity, such as anaphylactic reactions, hepatic toxicity (severe or clinically significant transaminase elevations), renal toxicity, etc.
    V. Other uses of Givlaari (givosiran) are considered investigational.

Medicare Coverage:

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for this drug. Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Givosiran (Givlaari) when the Horizon BCBSNJ Medical Policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.

Medicaid Coverage:

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Givosiran (Givlaari)
Givlaari (Givosiran)

References:
1. Givlaari [Prescribing Information]. Alnylam Pharmaceuticals, Inc., Cambridge, MA. November 2019. Available at: https://media.celgene.com/content/uploads/reblozyl-pi.pdf

2. ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP). Available at: https://clinicaltrials.gov/ct2/show/NCT03338816

3. Givlaari. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. c2019 [2019 November 25]. Available from www.clinicalpharmacology.com.

Codes:

(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

HCPCS

C9056
J0223

* CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.
_________________________________________________________________________________________

Medical policies can be highly technical and are designed for use by the Horizon BCBSNJ professional staff in making coverage determinations. Members referring to this policy should discuss it with their treating physician, and should refer to their specific benefit plan for the terms, conditions, limitations and exclusions of their coverage.

The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy

____________________________________________________________________________________________________________________________