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Date Printed: June 24, 2017: 11:33 AM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-29

Original Effective Date: 03/15/15

Reviewed: 05/10/17

Revised: 06/15/17

Next Review: 05/09/18

Subject: Lumacaftor/Ivacaftor (Orkambi™) Capsule

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Lumacaftor and ivacaftor combination therapy was approved by the U.S. Food and Drug Administration (FDA) in July 2015 for use in patients aged 12 years and older with cystic fibrosis (CF) who are homozygous for the F508 del mutation in the CF transmembrane conductance regulator (CFTR) gene. The approval was expanded to included children 6 years and older in September 2016. In the US, this mutation represents approximately 8,500 patients with CF (half of the total CF population). There is currently no treatment available that specifically targets this particular mutation; current treatment options only address complications associated with the disease. Prior to FDA approval, lumacaftor/ivacaftor was designated as an Orphan Drug for its FDA-approved indication.

Lumacaftor is a CFTR corrector and ivacaftor is a CFTR potentiator. The efficacy of lumacaftor/ivacaftor in patients with CF who are homozygous for the F508del mutation in the CFTR gene was evaluated in two randomized, double-blind, placebo-controlled, 24-week clinical trials (Trials 1 and 2) in 1108 clinically stable patients with CF of whom 369 patients received lumacaftor/ivacaftor twice daily.

Trial 1 evaluated 549 patients with CF who were aged 12 years and older (mean age 25.1 years) with ppFEV1 at screening between 40-90 [mean ppFEV1 60.7 at baseline (range: 31.1 to 94.0)]. Trial 2 evaluated 559 patients aged 12 years and older (mean age 25.0 years) with ppFEV1 at screening between 40-90 [mean ppFEV1 60.5 at baseline (range: 31.3 to 99.8)].

Patients in both trials were randomized 1:1:1 to receive either lumacaftor 400 mg q12h/ivacaftor 250 mg q12h; or lumacaftor 600 mg once daily/ivacaftor 250 mg q12h or placebo. Patients took the study drug with fat-containing food for 24 weeks in addition to their prescribed CF therapies (e.g., bronchodilators, inhaled antibiotics, dornase alfa, and hypertonic saline).

The primary efficacy endpoint in both trials was change in lung function as determined by absolute change from baseline in ppFEV1 at Week 24, assessed as the average of the treatment effects at Week 16 and at Week 24. In both trials, treatment with lumacaftor/ivacaftor resulted in a statistically significant improvement in ppFEV1. The treatment difference between lumacaftor/ivacaftor and placebo for the mean absolute change in ppFEV1 from baseline at Week 24 (assessed as the average of the treatment effects at Week 16 and at Week 24) was 2.6 percentage points [95% CI (1.2, 4.0)] in Trial 1 (P=0.0003) and 3.0 percentage points [95% CI (1.6, 4.4)] in Trial 2 (P<0.0001). These changes persisted throughout the 24-week treatment period (Figure 1). Improvements in ppFEV1 were observed regardless of age, disease severity, sex, and geographic region.

POSITION STATEMENT:

Initiation of lumacaftor/ivacaftor (Orkambi™) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with cystic fibrosis (CF)

2. Member has a homozygous F508 del mutation in the CF transmembrane conductance regulator (CFTR) gene confirmed by an FDA-cleared cystic fibrosis mutation test – laboratory documentation must be provided

3. Member’s baseline forced expiratory volume in one second (FEV1) has been documented in the medical record

4. Lumacaftor-ivacaftor is not administered in combination with single-agent ivacaftor (Kalydeco)

5. Dose does not exceed four capsules per day

6. Member is 6 years of age or older

Approval duration: 6 months

Continuation of lumacaftor/ivacaftor (Orkambi™) meets the definition of medical necessity for members meeting ALL of the following criteria:

1. Authorization/reauthorization has been previously approved by Florida Blue OR the member has previously met all indication-specific initiation criteria

2. Member meets ONE of the following:

a. Member demonstrates a clinically meaningful response to treatment with lumacaftor/ivacaftor as indicated by any of the following:

i. Improvement in forced expiratory volume in one second (FEV1) – documentation must be provided

ii. Improvement in body mass index (BMI) – documentation must be provided

iii. Reduction in pulmonary exacerbations – documentation must be provided

iv. Improvement in quality of life as demonstrated by Cystic Fibrosis Questionnaire- Revised (CFQ-R) respiratory domain score – documentation must be provided

b. Member currently demonstrates a beneficial response to treatment with lumacaftor/ivacaftor AND has been receiving treatment for a minimum of 18 months

3. Lumacaftor-ivacaftor is not administered in combination with single-agent ivacaftor (Kalydeco)

4. Dose does not exceed four capsules per day

5. Member is 6 years of age or older

Approval duration: 1 year

NOTE: If the member’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of any mutation. Quest Diagnostics┬« can perform the CF mutation test. Additionally, documentation of member’s mutation from the Cystic Fibrosis Foundation CF Patient Registry is acceptable in place of original laboratory documentation.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Age 12 years and older: Two tablets (each containing lumacaftor 200 mg/ivacaftor 125 mg) taken orally every 12 hours

• Age 6 through 11 years: Two tablets (each containing lumacaftor 100 mg/ivacaftor 125 mg) taken orally every 12 hours

Dose Adjustments

• Reduce dose in patients with moderate or severe hepatic impairment

• Reduce dose for the first week of treatment in patients takig strongCYP3A inhibitors

Drug Availability

• Tablets: lumacaftor 100 mg and ivacaftor 125 mg; lumacaftor 200 mg and ivacaftor 125 mg

PRECAUTIONS

Contraindications

None

Precautions/Warnings

• Liver-related events: Elevated transaminases (ALT/AST) have been observed in some cases associated with elevated bilirubin

• Respiratory events: Chest discomfort, dyspnea, and respiration abnormal were observed more commonly during initiation

• Drug interactions: Use with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index may decrease systemic exposure of the medicinal products and co-administration is not recommended

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J8499

Prescription drug, oral, non-chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity:

E84.0

Cystic fibrosis with pulmonary manifestations

E84.11

Meconium ileus in cystic fibrosis

E84.19

Cystic fibrosis with other intestinal manifestations

E84.8

Cystic fibrosis with other manifestations

E84.9

Cystic fibrosis, unspecified

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline revised date.

DEFINITIONS:

None

RELATED GUIDELINES:

Genetic Testing, 05-82000-28
Ivacaftor (Kalydeco TM) Oral, 09-J1000-68

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017 Aug 7]. Available from: http://www.clinicalpharmacology.com/.
  2. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2017 Aug 7]. Available from: http://clinicaltrials.gov/.
  3. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017 Aug 7]. Available from: http://www.thomsonhc.com/.
  4. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Aug 7]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  5. Vertex Pharmaceuticals. Kalydeco (ivacaftor). 2017 [cited 2017 Jan 3]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0ab0c9f8-3eee-4e0f-9f3f-c1e16aaffe25/.
  6. Vertex Pharmaceuticals. Orkambi (lumacaftor and ivacaftor) tablet. 2017 [cited 2017 Aug 7]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3fc1c40e-cfac-47a1-9e1a-61ead3570600/.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 05/10/17.

GUIDELINE UPDATE INFORMATION:

03/15/15

New Medical Coverage Guideline.

09/15/15

Revision to guideline; consisting of position statement, dosage/administration.

11/01/15

Revision: ICD-9 Codes deleted.

03/15/16

Review and revision; consisting of updating position statement.

04/15/16

Revision to guideline; consisting of updating position statement.

11/15/16

Revision to guideline; consisting of updating position statement, dosage/administration, description

03/15/17

Revision to guideline; consisting of updating position statement.

06/15/17

Review and revision to guideline; consisting of updating references.

Date Printed: June 24, 2017: 11:33 AM