Kalbitor® (ecallantide) (SQ formulation)

Last Review Date: n/a Dates Reviewed: Date of Origin: 08/27/2013 Prior Auth Available: √ Post-service edit: √ Medical Necessity Criteria Number: IC-0167

The medical necessity criteria were developed by ICORE Healthcare for the purpose of making clinical review determinations for requests for commonly used in various diseases. The clinical disciplines of oncology, hematology, rheumatology, neurology, internal medicine, pharmacy and nursing were consulted as part of the criteria development. The development followed an extensive literature search pertaining to established clinical guidelines and accepted prescribing patterns for each individual drug. The indications for the medications are consistent with FDA approved indications, CMS coverage guidelines, National Comprehensive Cancer Network (NCCN) guidelines and/or other published peer reviewed research literature.

I. Description: Kalbitor (ecallantide) is a selective, reversible human plasma inhibitor. Ecallantide binds to plasma kallikrein and blocks its binding site, inhibiting the conversion of HMW to . By directly inhibiting plasma kallikrein, ecallantide reduces the conversion of HMW kininogen to bradykinin and thereby treats symptoms of the disease during acute episodic attacks of HAE.

II. Length of Authorization: Coverage is provided for 12 months and will be eligible for renewal

III. Review Criteria: Treatment of acute attacks of Hereditary (HAE): o Patient must be at least 16 years of age; AND o Patient has the following clinical presentation consistent with HAE I: • Low C4 level (C4 less than 14 mg/dL; normal range 14 to 40 mg/dL, or C4 below the lower limit of normal as defined by the laboratory performing the test); AND • Low C1 inhibitor (C1INH) antigenic level (C1INH less than 19 mg/dL normal range 19 to 37 mg/dL, or C1INH antigenic level below the lower limit of normal as defined by the laboratory performing the test); AND • Patient has a family history of HAE; OR • Normal C1q level; OR o Patient has the following clinical presentation consistent with HAE II: • Normal C1INH antigenic level (C1INH greater than or equal to 19 mg/dL); AND • Low C4 level (C4 less than 14 mg/dL; normal range 14 to 40 mg/dL, or C4 below the lower limit of normal as defined by the laboratory performing the test); AND • Low C1INH functional level (functional C1INH less than 50 % or C1INH functional level below the lower limit of normal as defined by the laboratory performing the test);OR o Patient has the following clinical presentation consistent with HAE III: • Normal C1INH antigenic level (C1INH greater than or equal to 19 mg/dL); AND • Normal C4 level (C4 greater than or equal to 14 mg/dL); AND • Patient has a known HAE-causing C1INH mutation (i.e. mutation of coagulation factor XII gene); OR • Patient has a family history of HAE; AND o Patient has a history of moderate to severe cutaneous or abdominal attacks OR mild to severe airway swelling attacks of HAE (i.e. debilitating cutaneous/gastrointestinal symptoms OR laryngeal/pharyngeal/tongue swelling) ; AND o Confirmation the patient is avoiding the following possible triggers for HAE attacks: Page 1 of 4

Kalbitor® (ecallantide) Medical Necessity Criteria Number: Last Review Date: IC-0167

• Helicobacter pylori infections (confirmed by lab test) • estrogen-containing oral contraceptive agents OR hormone replacement therapy • antihypertensive agents containing ACE inhibitors

IV. Renewal Criteria: o Significant improvement in severity and duration of attacks have been achieved and sustained; AND o Absence of unacceptable toxicity from the drug. Examples of unaccaptable toxicity include hypersensitivity reactions.

V. Dosage/Administration: Indication Dose (HAE) 30 mg injected subcutaneously in three 10 mg injections. An additional dose of 30 mg may be administered if attack persists for a total of two 30 mg doses in 24 hours.

VI. Billing/Code Information: JCode: J1290 – Kalbitor (Dyax Corp) 10 mg injection: 1 billable unit = 1 mg

NDC: Kalbitor 10 mg – 47783-0101-xx (Dyax Corp)

Max Units (per dose and over time): Male 360 billable units per 28 days Female 360 billable units per 28 days

Quantity Limitations: Kalbitor 10 mg vial: 36 vials per 28 days

Covered Diagnosis: ICD-9 Codes Diagnosis 277.6 Other deficiencies of circulating enzymes

VII. Centers for Medicare and Medicaid Services (CMS): Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD): Jurisdiction(s): 9(N) NCD/LCD Document (s): L31475 ICD-9 Codes Diagnosis 277.6 OTHER DEFICIENCIES OF CIRCULATING ENZYMES Page 2 of 4

Kalbitor® (ecallantide) Medical Necessity Criteria Number: Last Review Date: IC-0167

VIII. Criteria Exclusions: o Treatment for diagnoses not FDA approved o All indications not described in Section III Review criteria are not covered and may be considered experimental or investigational. o Use of non-preferred products without previous trial and failure of all applicable preferred products per Health Plan

IX. Black Box Warnings/Contraindications: Black Box Warnings o May cause anaphylaxis and other hypersensitivity reactions. o Should be administered by a healthcare professional with appropriate medical support to manage anaphylaxis and hereditary angioedema. o Patients who have known clinical hypersensitivity to Kalbitor should be instructed not to receive additional doses of Kalbitor. Contraindications Do not use in patients with a known clinical hypersensitivity to Kalbitor (ecallantide).

X. References: 1. Kalbitor [package insert]. Burlington, MA; Dyax Corp; February 2012. Accessed August 2013. 2. Bygum A, Andersen KE, Mikkelsen CS. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. Mar-Apr 2009;19(2):147-151. 3. Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24. 4. Craig T, Aygören-Pürsün E, Bork K, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012 Dec;5(12):182-99. 5. Gompels MM, Lock RJ, Abinun M, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005;139(3):379. 6. First Coast Service Options, Inc. Local Coverage Determination (LCD): Selective Treatment of HAE with Cinryze ™, Berinert ® and Ecallantide (L31475). Centers for Medicare & Medicaid Services, Inc. Updated on 01/05/2011 with effective date 01/23/2011. Accessed August 2013.

XI. Appendix:

Medicare Part B Administrative Contractor (MAC) Jurisdictions Jurisdiction Applicable State/US Territory Contractor 1 (E) CA,HI, NV, AS, GU, CNMI Palmetto GBA F AK, WA, OR, ID, ND, SD, MT, WY, UT, AZ Noridian Administrative Services (NAS) 6 MN, WI, IL Wisconsin Physicians Service (WPS) 5 KS, NE, IA, MO Wisconsin Physicians Service (WPS)

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Kalbitor® (ecallantide) Medical Necessity Criteria Number: Last Review Date: IC-0167

H LA, AR, MS, TX, OK, CO, NM Novitas Solutions 15 KY, OH CGS Administrators 8 MI, IN Wisconsin Physicians Service (WPS) 10 (J) TN, GA, AL Cahaba Government Benefit Administrators 13 NY, CT National Government Services (NGS) 14 MA, RI, VT, ME, NH National Heritage Insurance Corporation (NHIC) 12 (L) DE, MD, PA, NJ, DC Novitas Solutions 11 (M) NC, SC, VA, WV Palmetto GBA 9 (N) FL, PR, VI First Coast Service Options

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