Archived Policies - Prescription Drugs


Reslizumab (CINQAIR)

Number:RX501.083

Effective Date:10-01-2016

End Date:10-14-2017

Coverage:

Medical policies are a set of written guidelines that support current standards of practice. They are based on current peer-reviewed scientific literature. A requested therapy must be proven effective for the relevant diagnosis or procedure. For drug therapy, the proposed dose, frequency and duration of therapy must be consistent with recommendations in at least one authoritative source. This medical policy is supported by FDA-approved labeling and nationally recognized authoritative references. These references include, but are not limited to: MCG care guidelines, Hayes, DrugDex (IIb level of evidence or higher), NCCN Guidelines (IIb level of evidence or higher), NCCN Compendia (IIb level of evidence or higher), professional society guidelines, and CMS coverage policy.

Reslizumab (CINQAIR®) may be considered medically necessary for add-on maintenance treatment of patients with severe eosinophilic asthma for up to 12 months when ALL the following criteria are met:

Patient is 18 years and older; AND

Patient meets the definition of severe asthma as defined by the following:

12 months of treatment with high-dose inhaled corticosteroid (ICS) in combination with at least one controller medication (e.g., long-acting beta2-agonist [LABA], leukotriene receptor antagonist [LTRA], or theophylline) for the previous year or systemic corticosteroids for 50% or more of the previous year to prevent asthma from becoming uncontrolled or remaining uncontrolled; AND

A pretreatment FEV1 less than 80% predicted; AND

History of 1 or more exacerbations requiring systemic glucocorticoids while being treated with fluticasone propionate 880μg or more or its equivalent in the last year; AND

Patient has eosinophilic phenotype as determined by blood eosinophil count (in the absence of other potential causes of eosinophilia, including hypereosinophilic syndromes, neoplastic disease, and known or suspected parasitic infection) ≥ 400 cells/μL (See NOTE) (within 3 to 4 weeks of dosing).

NOTE 1: 1 microliter (μL) is equal to 1 cubic millimeter (mm3).

Reslizumab (CINQAIR®) may be considered medically necessary for patients with severe eosinophilic asthma for continuation of therapy after 12 months when treatment has resulted in clinical improvement as documented by one or more of the following:

Decreased utilization of rescue medications; OR

Decreased frequency of exacerbations (defined as worsening of asthma that requires an increase in ICS dose or treatment with systemic corticosteroids); OR

Increase in predicted FEV1 from pretreatment baseline; OR

Reduction in reported asthma-related symptoms, such as, asthmatic symptoms upon awakening, coughing, fatigue, shortness of breath, sleep disturbance, or wheezing.

Reslizumab (CINQAIR®) is considered experimental, investigational and/or unproven when above criteria is not met as outlined and ALL other indications, including but not limited to:

Aspirin-exacerbated respiratory disease (AERD); OR

Atopic dermatitis; OR

Eosinophilic esophagitis; OR

Eosinophilic granulomatosis with polyangiitis (EGPA) (Churg-Strauss syndrome); OR

Nasal polyposis; OR

Hypereosinophilic syndromes (other than severe eosinophilic asthma); OR

Relief of acute bronchospasm; OR

Status asthmaticus.

Description:

Asthma is a chronic lung disease that inflames and narrows the airways. In 2013, The European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force on severe asthma updated the definition of severe asthma that states the following: When the diagnosis of asthma is confirmed and addressed, severe asthma is defined as “asthma which required treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or) systemic corticosteroids to prevent it from becoming “uncontrolled” or which remains ‘uncontrolled’ despite this therapy.” Severe asthma is heterogeneous condition consisting of phenotypes such as eosinophilic phenotype. (1)

ERS/ATS Task Force defines uncontrolled asthma as at least one of the following:

1) Poor symptom control: Asthma Control Questionnaire (ACQ) consistently >1.5, Asthma Control Test (ACT) <20 (or not well controlled by National Asthma Education and Prevention Program (NAEPP)/Global Initiative for Asthma (GINA) guidelines.

2) Frequent severe exacerbations: two or more bursts of systemic corticosteroids (CS) (> 3 days each) in the previous year.

3) Serious exacerbations: at least one hospitalization, intensive care unit (ICU) stay or mechanical ventilation in the previous year.

4) Airflow limitation: after appropriate bronchodilator withhold FEV1 < 80% predicted (in the face of reduced forced expiratory volume-one second (FEV1)/forced vital capacity (FVC) defined as less than the lower limit of normal). (1)

Reslizumab (CINQAIR®) is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody (IgG4κ). It is produced by recombinant deoxyribonucleic acid (DNA) technology in murine myeloma non-secreting 0 (NS0) cells. IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils that binds to IL-5 with a dissociation constant of 81 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil surface. By inhibiting IL-5 signaling, reduces the production and survival of eosinophils. (2,3)

Regulatory Status

On March 23, 2016, the U. S. Food and Drug Administration (FDA) approved reslizumab (CINQAIR®) for the add-on maintenance treatment of individuals with severe asthma with an eosinophilic phenotype who are age 18 years and older. FDA dosage is noted as 3/mg/kg once every 4 weeks by intravenous infusion only (not intravenous push or bolus), infused over a 20-50 minute period in a healthcare setting by a healthcare professional prepared to manage anaphylaxis. Reslizumab is not indicated for treatment of other eosinophilic conditions or relief of acute bronchospasms or status asthmaticus. (2)

Rationale:

Approval of reslizumab (CINQAIR®) was based on 4 randomized, double-blind, placebo-controlled studies (Studies I-IV). Studies I and II, were 52-week identical studies that included 953 participants 12 to 75 years of age (mean age, 47 years [all participants]). These 2 multicenter, phase III trials required participants to have blood eosinophil levels > 400 cells/µl (within 3 to 4 weeks of dosing), asthma inadequately controlled by medium-to high-doses of inhaled corticosteroid (ICS) therapy, and 1 or more asthma exacerbations in the previous year. Patients were randomly assigned (1:1) to receive either intravenous reslizumab (3.0 mg/kg) or placebo every 4 weeks for 52 weeks. In both studies, patients receiving reslizumab had a significant reduction in the frequency of asthma exacerbations (study I: rate ratio [RR] 050 [95% CI 037-067]; study II: 041 [028-059]; both p<00001) compared with those receiving placebo. Castro et al. reports these results support the use of reslizumab in patients with asthma and elevated blood eosinophil counts who are inadequately controlled on inhaled corticosteroid-based therapy. (2,3)

Study III and Study IV were 16-week studies with a primary endpoint of improvement in forced expiratory volume in 1 second (FEV1) with reslizumab versus placebo. Study III included 315 participants ages 12 to 75 years who were required to have a blood eosinophil count of ≥ 400 cells/µl at screening (within 3 to 4 weeks of dosing). Intravenous reslizumab (3.0 mg/kg) administered once every 4 weeks for a total of 4 doses was evaluated compared with placebo. Bjermer et al. reported the following results: reslizumab significantly improved FEV1 (difference vs placebo [reslizumab 0.3 and 3.0 mg/kg]: 115 mL [95% CI 16-215; P= .0237] and 160 mL [95% CI 60-259; P= .0018]). Clinically meaningful increases in forced vital capacity (FVC) (130 mL) and FEF 25-75% (233 mL/s) were observed with reslizumab 3.0 mg/kg. Reslizumab improved Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ) versus placebo (greater effects seen with 3.0 mg/kg; P<0.05). The minimally important difference was reached for AQLQ (reslizumab 3.0 mg/kg) but not ACQ. Asthma Symptom Utility Index and short-acting beta-agonist (SABA) use were improved with reslizumab. The most common adverse events were asthma worsening, headache, and nasopharyngitis; most were mild-to-moderate in severity. Authors concluded that reslizumab improved lung function, asthma control and symptoms, and quality of life, and was well tolerated in patients with inadequately controlled asthma (despite standard therapy), and elevated blood eosinophils. Overall, the 3.0 mg/kg dose of reslizumab provided greater improvements in asthma outcomes (vs 0.3 mg/kg), with comparable safety. (4) Study IV included 496 participants ages 18 to 75 with uncontrolled asthma defined as having an ACQ score of 1.5 or more and treated with at least a medium dose of ICSs. Study IV was the only study to test reslizumab 3.0 mg/kg in asthma participants unselected for baseline blood eosinophil levels (measured 3 to 4 weeks prior to dosing); association of treatment effect (i.e., difference between reslizumab and placebo in the change in FEV1 at week 16) and baseline blood eosinophils was not observed. (2,4-5)

The demographics and baseline characteristics of these 4 studies is provided in Table 1.

Table 1: Demographics and Baseline Characteristics of Patients in Asthma Studies (2)

Study I

(N=489)

Study II

(N=464)

Study III

(N=315)

Study IV

(N=496)

Mean age (yr)

47

47

44

45

Female (%)

63

63

58

64

White (%)

73

73

81

67

Duration of asthma, mean (yr)

19

18

20

26

Baseline Pre-bronchodilator FEV1, mean % predicteda

64

69

70

67

Baseline Reversibility, mean % ΔFEV1 post-SABAa

26

28

25

26

Baseline mean blood eosinophil count/mcLa

660

649

614

280

Mean number of exacerbations in previous year

1.99

1.94

2.03

1.86

a Baseline for lung function and eosinophil count is the day of randomization.

FEV1=forced expiratory volume in 1 second; SABA=short-acting beta agonist

All patients had to be on inhaled corticosteroid (ICS) background therapy and could have been receiving any combination of background therapies (ICS with or without another controller [non-ICS and/or OCS]).

Summary

Reslizumab (CINQAIR®) demonstrated reduced exacerbations rates and improved forced expiratory volume in 1 second (FEV1) when compared with placebo in patients with baseline eosinophil levels > 400 cells/µl diagnosed with severe eosinophilic asthma 18 years of age and older. Reslizumab is being investigated for other indications, to date the U. S. Food and Drug Administration (FDA) has not approved reslizumab for any additional indications.

Contract:

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coding:

CODING:

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.

CPT/HCPCS/ICD-9/ICD-10 Codes

The following codes may be applicable to this Medical policy and may not be all inclusive.

CPT Codes

N/A

HCPCS Codes

J2786, [Deleted 1/2017: C9481]

ICD-9 Diagnosis Codes

Refer to the ICD-9-CM manual

ICD-9 Procedure Codes

Refer to the ICD-9-CM manual

ICD-10 Diagnosis Codes

Refer to the ICD-10-CM manual

ICD-10 Procedure Codes

Refer to the ICD-10-CM manual


Medicare Coverage:

The information contained in this section is for informational purposes only. HCSC makes no representation as to the accuracy of this information. It is not to be used for claims adjudication for HCSC Plans.

The Centers for Medicare and Medicaid Services (CMS) does not have a national Medicare coverage position. Coverage may be subject to local carrier discretion.

A national coverage position for Medicare may have been developed since this medical policy document was written. See Medicare's National Coverage at <http://www.cms.hhs.gov>.

References:

1) Chung KF,Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. Feb 2014; 43(2):343-73. PMID 24337046

2) FDA - CINQAIR® (Reslizumab) - Product Label. Food and Drug Administration (March 2016). Available at <http://www.fda.gov> (accessed - 2016 September 15).

3) Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebocontrolled, phase 3 trials. Lancet Respir Med. May 2015; 3(5):355-66. PMID 25736990

4) Bjermer L, Lemiere C, Maspero J, et al. Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels: a Randomized Phase 3 Study. Chest. Apr 2016; pii: S0012-3692(16)47551-3. PMID 27056586

5) Reslizumab (CINQAIR®). Specialty Pharmacy Report – 2016. Chicago, Illinois: Blue Cross Blue Shield Association. (February 2016): 1-36.

Policy History:

Date Reason
10/1/2016 New medical document. Reslizumab (CINQAIR®) may be considered medically necessary for add-on maintenance treatment of patients with severe eosinophilic asthma when ALL the following criteria are met: 1) Patient is 18 years and older AND 2) Patient meets the definition of severe asthma as defined by the following: 12 months of treatment with high-dose inhaled corticosteroid (ICS) in combination with at least one controller medication (e.g., long-acting beta2-agonist [LABA], leukotriene receptor antagonist [LTRA], or theophylline) for the previous year or systemic corticosteroids for 50% or more of the previous year to prevent asthma from becoming uncontrolled or remaining uncontrolled; 3) a pretreatment FEV 1 less than 80% predicted; 4) History of 1 or more exacerbations requiring systemic glucocorticoids while being treated with fluticasone propionate 880μg or more or its equivalent in the last year; AND 5) Patient has eosinophilic phenotype as determined by blood eosinophil count (in the absence of other potential causes of eosinophilia, including hypereosinophilic syndromes, neoplastic disease, and known or suspected parasitic infection) ≥ 400 cells/μL (See NOTE 1) (within 3 to 4 weeks of dosing). NOTE 1: Patients who do not meet the criteria for uncontrolled asthma, but whose asthma worsens on tapering off corticosteroids, will also meet this definition of severe asthma. For definition of uncontrolled asthma see description section. NOTE 1: 1 microliter (μL ) is equal to 1 cubic millimeter (mm3). Reslizumab (CINQAIR®) may be considered medically necessary for patients with severe eosinophilic asthma for continuation of therapy after 12 months when treatment has resulted in clinical improvement as documented by one or more of the following: 1) Decreased utilization of rescue medications; OR 2) decreased frequency of exacerbations (defined as worsening of asthma that requires an increase in ICS dose or treatment with systemic corticosteroids); OR 3) Increase in predicted FEV 1 from pretreatment baseline; OR 4) Reduction in reported asthma-related symptoms, such as, asthmatic symptoms upon awakening, coughing, fatigue, shortness of breath, sleep disturbance, or wheezing. Reslizumab (CINQAIR®) is considered experimental, investigational and/or unproven when above criteria is not met as outlined and ALL other indications.

Archived Document(s):

Title:Effective Date:End Date:
Reslizumab (CINQAIR)10-15-201709-30-2018
Reslizumab (CINQAIR)10-01-201610-14-2017
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