Drug Monograph Drug/Drug Class: Omontys (Peginesatide Injection) Solution / Colony Stimulating Factors Prepared For: MO Healthne

Drug Monograph

Drug/Drug Omontys™ (peginesatide injection) Solution / Colony Class: Stimulating Factors

Prepared for: MO HealthNet Prepared by: Xerox Heritage, LLC.

New Criteria Revision of Existing Criteria Executive Summary

The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be made available on an open Purpose: access basis to prescribers, require a clinical edit or require prior authorization for use.

Each 1 ml multiple use vial of Omontys™ 10mg/ml contains 10mg of peginesatide for intravenous or subcutaneous administration. Each 2 ml multiple use vial of Omontys™ 10mg/ml contains 20mg of peginesatide for Dosage Forms & intravenous or subcutaneous administration. Manufacturer:

Takeda Pharmaceuticals North America Inc One Takeda Parkway Deerfield, IL 60015

Summary of This drug is being considered for inclusion into the state specific preferred Findings: drug list.

Status Prior Authorization (PA) Required Open Access Recommendation: Clinical Edit PDL Product

Type of PA Increased Risk of ADE No PA Required Criteria: Appropriate Indications Under Solicitation

Purpose The purpose of this monograph is to provide a review of new therapy to determine whether the reviewed drug should be considered a prior authorization drug, a clinical edit drug or an open access drug. While prescription expenditures are increasing at double-digit rates, payors are evaluating ways to control these costs by influencing prescriber behavior and guide appropriate medication usage. This review will assist in the achievement of qualitative and economic goals related to health care resource utilization. Restricting the use of certain medications can reduce costs by requiring documentation of appropriate indications for use, and where appropriate, encourage the use of less expensive agents within a drug class.

Introduction Anemia is a common complication in dialysis patients due to a lack of erythropoietin production in the kidneys. Nearly 95% of dialysis patients in the United States are being treated for anemia.

Dosage Form(s) 1 Each 1 ml multiple use vial of Omontys™ 10mg/ml contains 10mg of peginesatide for intravenous or subcutaneous administration. Each 2 ml multiple use vial of Omontys™ 10mg/ml contains 20mg of peginesatide for intravenous or subcutaneous administration.

Manufacturer Takeda Pharmaceuticals North America Inc One Takeda Parkway Deerfield, IL 60015

Indication(s) 1 Omontys is indicated for the treatment of anemia due to chronic kidney disease in adult patients on dialysis.

1-4 Clinical Efficacy (mechanism of action/pharmacology, comparative efficacy) Omontys™ is an erythropoiesis-stimulating agent (ESA) that is a synthetic, pegylated dimeric peptide comprised of two identical, 21-amino acid chains covalently bonded to a linker derived from iminodiacetic acid and beta-alanine. It binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in vitro.

PHARMACOKINETICS (1)

Peginesatide Protein binding None

Volume of 34.9 mL/kg distribution

Metabolism Not metabolized

Excretion Urine

Half-life 25 to 53 hours

The approval of Omontys™ was primarily based upon two randomized, active-controlled, open- label clinical trials (EMERALD 1 and 2) involving 1608 patients with CKD undergoing dialysis with hemoglobin levels stabilized by epoetin alfa or epoetin beta. Results from these studies showed that treatment with Omontys™ was as effective as epoetin in maintaining hemoglobin levels within the prespecified range of 10 to 12 grams/dL.

STUDY DESIGN Two multicenter, randomized, active-controlled, open-label clinical trials (n=1608). INCLUSION Adult CKD patients with anemia undergoing dialysis with hemoglobin CRITERIA levels stabilized with epoetin alfa or epoetin beta. EXCLUSION Not specified. CRITERIA TREATMENT Patients were randomized (2:1) to receive Omontys™ once monthly or REGIMEN to continue the current ESA treatment 1 to 3 times per week. The Omontys™starting dose was based on the total weekly ESA dose during the last week of the screening period. The primary efficacy endpoint for each study was the change in hemoglobin from baseline to the evaluation period (weeks 29 to 36) using a noninferiority comparison with epoetin. In Study 1, patients received epoetin IV and continued to use this route after randomization to either Omontys™ or epoetin. The average patient exposure year (PEY) per patient was 1.14 years for Omontys™ and 1.25 years for epoetin. In Study 2, the previous route of administration for epoetin (IV or subQ) was continued. The average PEY per patient was 1.17 years for Omontys™and 1.16 years for epoetin. The median dose of Omontys™ was 0.07 mg/kg/month as a single dose and the median dose of epoetin was 113 units/kg/week given in 1 to 3 doses. RESULTS Treatment with Omontys™ once monthly and treatment with epoetin 1 to 3 times per week maintained hemoglobin concentrations within the prespecified hemoglobin range of 10 to 12 grams/dL. In both studies, the proportion of patients receiving transfusions was similar in each treatment group. In Study 1, the mean change in hemoglobin from baseline to weeks 29 to 36 was -0.24 grams/dL and -0.09 grams/dL for patients receiving Omontys™ and epoetin, respectively (95% CI, -0.30 to -0.01 grams/dL). In Study 2, the mean change in hemoglobin from baseline to weeks 29 to 36 was -0.07 grams/dL and -0.17 grams/dL in the same groups, respectively (95% CI, -0.05 to 0.26 grams/dL). SAFETY The most common adverse effects with Omontys™ were diarrhea, vomiting, hypertension, and arthralgia.

Contraindication1 . Uncontrolled hypertension.

Warnings and Precautions1 . Risk of increased mortality, myocardial infarction, stroke, and thromboembolism if target hemoglobin level is greater than 11 g/dL; caution advised with coexistent cardiovascular disease and stroke.

. Control hypertension prior to initiation and during treatment. . Not indicated and recommended for anemia or reduction of RBC transfusions in cancer patients due to risk of increased mortality and/or tumor progression or recurrence. . If a patient has no response or a loss of response to therapy, evaluate for iron deficiency, infection, inflammation, bleeding, or antibodies to peginesatide; in the absence of antibodies, adjust dose. . Patients may require increased anticoagulation with heparin to prevent clotting during hemodialysis.

Adverse Effects1

Epoetin alfa/beta Most common, >= 10% Peginesatide (n=1066) (n=542)

Diarrhea 18.40% 15.90% Dyspnea 18.40% 19.40% Nausea 17.40% 19.60%

Arteriovenous fistula complication 16.10% 16.60%

Cough 15.90% 16.60% Headache 15.40% 15.90%

Muscle spasms 15.30% 17.20%

Vomiting 15.30% 13.30% Hypotension 14.20% 14.60% Hypertension 13.20% 11.40% Pyrexia 12.20% 14.00% Hyperkalemia 11.40% 11.80%

Upper respiratory tract infection 11.00% 12.40%

Back pain 10.90% 11.30%

Pain in extremity 10.90% 12.70%

Procedural hypotension 10.90% 12.50%

Arthralgia 10.70% 9.80%

Drug Interactions1 . None noted

Dosage and Administration1 Initial dose is 0.04 mg/kg, either subQ or IV, once monthly for patients not already receiving an ESA. If converting from another ESA, dose once monthly based on the total weekly epoetin or darbepoetin alfa dose at the time of conversion.

Cost Comparisons (at commonly used dosages) COST (WAC)*

GENERIC BRAND MANUFACTURER STRENGTH DOSE** COST/ NAME NAME MONTH Peginesatide Omontys Takeda 10 mg/mL, 5 mg/ month $ 545.91 injection multidose vial Epoetin alfa Epogen Amgen 20,000 2200 units 3 $ 345.31 injection units/mL, times/wk multidose vial Epoetin alfa Procrit Janssen 20,000 2200 units 3 $ 446.76 injection units/mL, times/wk multidose vial Darbepoetin Aranesp Amgen 25 mcg/mL, 25 mcg/ wk $ 576.68 alfa injection single-dose vial 25 mcg/0.42 25 mcg/ wk $ 576.68 mL, prefilled syringe

Missouri Maximum Allowable Cost Conclusion Omontys™ is an ESA that has demonstrated efficacy for the treatment of anemia due to CKD in adult patients on dialysis. Omontys™ is a synthetic, pegylated, peptide-based ESA that is dosed once monthly. It is the first approved ESA for this condition since 2001, and may offer cost advantages due to the monthly dosage schedule. The FDA approved Omontys™with a Risk Evaluation and Mitigation Strategy (REMS) that includes educational elements for healthcare professionals. In addition, the manufacturer has several postmarketing requirements that include an observational and randomized controlled trial to evaluate cardiovascular safety and long-term safety in adult patients on dialysis and initiation of pediatric studies.

Recommendation This drug is being considered for inclusion in the state specific Preferred Drug List (PDL).

References 1. Product Information: Omontys®, peginesatide injection. Takeda Pharmaceuticals America, Inc., Deerfield, IL, 03/2012. 2. Green JM, Leu K, Worth A et al: Peginesatide and erythropoietin stimulate similar erythropoietin receptor-mediated signal transduction and gene induction events. Exp Hematol 2012 Mar 6 (Epub ahead of print).

3. Macdougall IC, Wiecek A, Tucker B et al: Dose-finding study of peginesatide for anemia correction in chronic kidney disease patients. Clin J Am Soc Nephrol 2011; 6(11):2579- 2586. 4. Doss S & Schiller B: Peginesatide: a potential erythropoiesis stimulating agent for the treatment of anemia of chronic renal failure. Nephrol Nurs J 2010; 37(6):617-626.

Prepared by: Ashley Capps, PharmD Candidate Date: August 16, 2012