Hereditary Angioedema - BMC HealthNet Plan

BMCHP.ORG1-888-566-0008WELLSENSE.ORGCLINICAL COVERAGE GUIDELINES – Hereditary AngioedemaBMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and WellSense Health Plan in New Hampshire. Boston Medical Center HealthNet Plan andWell Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.Policy ApplicabilityBoston Medical Center HealthNet Plan Well Sense Health PlanMassHealthNew Hampshire MedicaidCommonwealth CareCommercialIntegrated Care ProgramEffective Date: 07/01/2013Policy Number: 9.021Policy Effective Date: 09/10/2009Last Review Date: 03/14/2013Approved by: Pharmacy and Therapeutics CommitteePolicy Owner/Title: Pharmacy ServicesSummary:BMC HealthNet Plan will authorize coverage of Berinert ® , Cinryze TM , Firazyr ® , andKalbitor ® when appropriate criteria are met.Description of Item or Service:Hereditary Angioedema (HAE) is a rare genetic disorder resulting from either low levelsof C1-esterase inhibitor or dysfunctional C1-esterase inhibitor (C1-INH). C1-INH is anThis guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.1 of 7BMC HealthNet Plan – Hereditary Angioedema

important regulator in bradykinin production via the Factor XII/kallikrein proteolyticcascade. Low levels of C1-INH causes excess bradykinin that leads to leaky bloodvessels and fluid accumulation in body tissues resulting in HAE symptoms. Clinicalimplications of HAE include recurrent angioedema affecting the upper gastrointestinaland respiratory tracts. Laryngeal edema can be fatal if symptoms are not recognized andtreated promptly.Approaches to treatment of HAE include acute treatment of angioedema attacks, shorttermprophylaxis (i.e. dental procedures, surgery, intubation), and long term prophylaxisfor patients that experience more than one severe event per month or are disabled morethan 5 days per month. All patients with HAE should receive education on triggeravoidance (e.g. facial trauma, avoidance of certain medications) and a written plan fortreatment of acute attacks that can be used in emergency department care.There are currently three medications FDA approved for the treatment of HAE:Berinert ® , Firazyr ® and Kalbitor ® . Cinryze TM is indicated for the prevention of HAEattacks. Berinert ® and Cinryze TM are both C1-esterase inhibitors. Firazyr ® and Kalbitor ®both modulate bradykinin activity; Firazyr ® is a selective bradykinin B2 receptorantagonist and Kalbitor ® inhibits plasma kallikrein activity. Cinryze TM and Berinert ® areadministered by intravenous infusion, while Kalbitor ® and Firazyr ® are administeredsubcutaneously. Berinert ® , Cinryze TM and Firazyr ® can be self-administered; Kalbitor ®requires administration by a healthcare provider.Specifically, product labeling for Kalbitor ® contains a black box warning stating that dueto the risk of anaphylaxis, Kalbitor ® should only be administered by a healthcareprofessional with appropriate medical support to manage anaphylaxis and hereditaryangioedema. The manufacturer of Kalbitor ® (Dyax) is required by the FDA toparticipate in the Risk Evaluation and Mitigation Strategy Program (REMS).Other medications used for treatment and prophylaxis of HAE include attenuatedandrogens (danazol, oxandrolone, methyltestosterone), antifibrinolytic therapy (oraltranexamic acid, oral aminocaproic acid), and fresh frozen plasma (only useful in shortterm prophylaxis). Oral tranexamic acid, the preferred antifibrinolytic therapy inEurope, was approved for use in the United States under the brand name Lysteda ® inNovember 2009 for the treatment of heavy menstrual bleeding.This guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.2 of 7BMC HealthNet Plan – Hereditary Angioedema

Attenuated androgens have been shown to be effective for treatment and prophylaxis ofHAE, and are a reasonable first line option given their widespread availability and lowcost relative to C1 esterase inhibitor. Antifibrinolytic agents have also been shown to beeffective, but are considered to be less effective than androgens and are not addressed inthe 2011 consensus report from the Hereditary Angioedema International WorkingGroup.Clinical Guideline Statement:BMC HealthNet Plan may authorize coverage of Berinert ® , Cinryze TM , Firazyr ® , andKalbitor ® for members meeting the following criteria:Prior AuthorizationA prior authorization request will be required for all prescriptions for Berinert ® ,Cinryze TM , Firazyr ® , and Kalbitor ® . These requests will be approved when the followingcriteria are met:MedicationPrior Authorization CriteriaInitial Therapy (Duration of Approval – Maximum of 3 months)All of the following must be documented for Berinert ® , Cinryze TM , Firazyr ® , andKalbitor ® :1. The prescriber must be a specialist in Allergy or Immunology; AND2. The member must have a confirmed diagnosis of HAE* supported by results ofgenetic testing or laboratory tests indicating normal C1q levels with C4 and C1inhibitor levels below the limits of the laboratory’s reference range (antigenic orfunctional levels). Baseline frequency of HAE attacks must be documented.In addition to the above, the specified criteria below must also be met for each drug:Berinert ®3. Documentation that the member requires treatment for acuteHAE attacks; AND4. The member must be at least 12 years of age; AND.5. The member must have a history of acute facial, laryngeal, orgastrointestinal angioedema attacks due to HAEThis guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.3 of 7BMC HealthNet Plan – Hereditary Angioedema

Firazyr ®Kalbitor ®3. Documentation that the member requires treatment for acuteHAE attacks; AND4. The member must be at least 18 years of age; AND5. The member must have a history of acute facial, laryngeal, orgastrointestinal angioedema attacks due to HAE3. Documentation that the member requires treatment for acuteHAE attacks; AND4. The member must be at least16 years of age; AND5. The member must have a history of acute facial, laryngeal, orgastrointestinal angioedema attacks due to HAE; AND6. Documentation of the plan for medication administration by ahealthcare professional in a facility equipped to provideappropriate medical support to manage anaphylaxis andhereditary angioedema; AND7. Documentation that the member has received the medicationguide required as part of the FDA Risk Management Strategy(REMS) program for Kalbitor ®Cinryze TM3. Documentation that the member requires prophylactictreatment for HAE; AND4. The member must be at least 12 years of age; AND5. The member has failed or could not tolerate a trial of anattenuated androgen or has a documented medicalcontraindication to androgen therapy** (e.g. danazol,oxandrolone, methyltestosterone); AND6. The member must meet at least one of the following criteriafor long-term HAE prophylaxis:a. More than one severe event per monthb. More than 24 days per year affected by HAEc. History of a recurrent laryngeal attacksContinuation of Therapy (Duration of Approval – Maximum of 3 months)The prescriber must provide all of the following documentation for continuation ofBerinert ® , Cinryze TM , Firazyr ® and Kalbitor ® therapy:Cinryze TM1. Significant improvement in severity and duration of attackshave been achieved and sustained; ANDThis guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.4 of 7BMC HealthNet Plan – Hereditary Angioedema

Berinert ® ,Firazyr ® , andKalbitor ®2. Clinical documentation of functional improvement have beenachieved and sustained.1. Significant improvement in severity and duration of attackshave been achieved and sustained; AND2. The member is receiving prophylactic therapy with attenuatedandrogens or C1 INH if the member has filled Berinert ® ,Firazyr ® or Kalbitor ® more than once per month for 3 of thelast 6 months (as evidenced by pharmacy claims)3. Documentation of member adherence to prophylactic therapyfor HAE if applicable.*BMC HealthNet Plan will NOT approve coverage of Berinert ® , Cinryze TM , andKalbitor ® for the treatment or prevention of angioedema due to causes other thanHAE.**Adherence to prescribed androgen therapy must be confirmed by prescriptionclaims. If the member is new to BMC HealthNet Plan and does not have a prescriptionclaims history, the prescriber must certify that the member has been adherent to theprescribed androgen therapy.Quantity Limitations Apply – see Appendix AApplicable Coding:J-CodeMedicationJ0597 C1 esterase inhibitor (human), 10 units (Berinert ® )J0598 C1 esterase inhibitor (human) 10 units (Cinryze TM )J1290 Ecallantide 1mg (Kalbitor ® )--- Icantibant (Firazyr ® )Limitations:BMC HealthNet Plan will not approve coverage of Berinert ® , Cinryze TM , Firazyr ® andKalbitor ® in the following instances:1. When the above criteria are not met.This guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.5 of 7BMC HealthNet Plan – Hereditary Angioedema

Clinical Background Information and References:1. Zuraw B. Clinical Practice: Hereditary angioedema. N Engl J Med. 2008;359(10):1027-36.2. Bowen T, et al. 2010 International Consensus Algorithm for the Diagnosis,Therapy, and Management of Hereditary Angioedema. Allergy Asthma &Clinical Immunology. 2010; 6:24. Available at:http://www.aacijournal.com/content/pdf/1710-1492-6-24.pdf.3. Atkinson JP, Ciardi M, Sheffer AL. Prevention of attacks in hereditaryangioedema. UptoDate. Last updated September 20, 2012., Accessed February2013. Available from http://www.uptodate.com. .4. Atkinson JP, Ciardi M, Sheffer AL. Treatment of acute attacks in hereditaryangioedema. UptoDate. Last updated October 24, 2012., Accessed February 2013.Available from http://www.uptodate.com.5. Cinryze ® [package insert]. Exton (PA): ViroPharma Biologics, Inc.; July 2012.6. Berinert ® [package insert]. Kankakee (IL): CSL Behring LLC; July 2012.7. Kalbitor ® [package insert]. Burlington (MA): Dyax Corp.; February 2012.8. Firazyr ® [package insert]. Lexington (MA): Shire; August 2011.9. Sardana N, Craig TJ. Recent Advances in Management and Treatment ofHereditary Angioedema. Pediatrics. 2011;128:1173-1180.Appendix A: Quantity Limitations for Cinryze TMMedication NameQuantity LimitationCinryze TM 500 unit vials16 vials per 30 daysPolicy History:Effective Date: 09/10/2009Date of Review/Revision03/11/2010) – P&T Annual Review, criteria added for Berinert ® and Kalbitor ®03/10/2011 – P&T Annual Review, no changes required07/14/2011 – policy applied to Commercial03/08/2012 – P&T Annual Review, removed requirement of healthcare professionaladministration for Berinert ® , criteria added for Firazyr ®This guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.6 of 7BMC HealthNet Plan – Hereditary Angioedema

Last Review Date: 03/14/2013 – P&T Annual Review, removed prophylaxisrequirements for initial approval of Berinert ® , Kalbitor ® and Firazyr ® , added requirementof prophylaxis to COT criteria for Berinert ® , Kalbitor ® and Firazyr ® , updated criteria forlong-term prophylaxisNext Review Date: 03/13/2014Approval DatesRegulatory Approval: N/AInternal Approval:Initial approval by Pharmacy & Therapeutics Committee – September 10, 2009Authorizing entityN/AIMPORTANT NOTE:‣ Not all services are covered for all products or employer groups. This medical policyexpresses the Plan's determination of whether certain services or supplies are medicallynecessary, experimental or investigational or cosmetic. The Plan has reached theseconclusions based upon the regulatory status of the technology and a review of clinicalstudies published in peer-reviewed medical literature. Even though this policy mayindicate that a particular service or supply is considered covered or not covered, thisconclusion is not based upon the terms of a member’s particular benefit plan. Eachbenefit plan contains its own specific provisions for coverage and exclusions. Not allservices that are determined to be medically necessary will necessarily be coveredservices under the terms of a member’s benefit plan. Members and their providers needto consult the applicable benefit plan document (e.g., Evidence of Coverage) todetermine if there are any exclusions or other benefit limitations applicable to this serviceor supply. If there is a discrepancy between this medical policy and the benefit plandocument, the provisions of the benefit plan document will govern. In addition, this policyand the benefit plan document are subject to applicable state and federal laws that maymandate coverage for certain services and supplies.‣ To the extent applicable, this Policy and/or Procedure applies to BMCHP subcontractorsand downstream entities, if any, providing services with respect to BMCHP’s IntegratedCare Program.This guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. Theuse of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement isbased on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Planpolicies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider.Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the mostrecent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accreditingorganization guidelines and requirements, including NCQA.This document is subject to further revision in response to additional terms and requirements imposed under the Integrated CareProgram, including the ICP contract.BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire.Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan,Inc.7 of 7BMC HealthNet Plan – Hereditary Angioedema