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Date Printed: October 23, 2017: 02:15 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-J1000-68

Original Effective Date: 06/15/12

Reviewed: 5/10/17

Revised: 09/15/17

Subject: Ivacaftor (Kalydeco™) Oral

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.

           

Position Statement

Dosage/ Administration

Billing/Coding

Reimbursement

Program Exceptions

Definitions

           

Related Guidelines

Other

References

Updates

 

Previous Version

           

DESCRIPTION:

Ivacaftor (Kalydeco™) was approved by the US Food and Drug Administration (FDA) on January 31, 2012 for treatment of cystic fibrosis (CF) in persons who have any of the following mutations in the CF transmembrane conductance regulator (CFTR) gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H. CF is a life-threatening, multisystem genetic disorder characterized by progressive lung disease. The disorder is the result of mutations in the CFTR gene located on chromosome 7. CF is inherited as an autosomal recessive trait. In an individual with a mutated CFTR gene, the risk of developing CF is dependent upon the mutation(s) present. The most common mutation is F508del. Another well-known mutation is G551D. Since the identification of CFTR in 1989 almost 2,000 mutations have been identified.

Ivacaftor exerts its effects by increasing chloride transport by potentiating the channel-open probability (or gating) of the G55ID-CFTR protein (an epithelial cell chloride channel). It is the first drug that directly targets the defective CFTR protein instead of the cystic fibrosis symptoms. In clinical studies of ivacaftor, it was ineffective in subjects who were homozygous for the F508del mutation in the CFTR gene; as such, it should not be used in this population. Ivacaftor is FDA-approved for use in children age 2 years of age and older.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of ivacaftor (Kalydeco) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member has a diagnosis of cystic fibrosis (CF)

2. Member has any of the following mutations on the CF transmembrane conductance regulator (CFTR) gene confirmed by an FDA-cleared cystic fibrosis mutation test – laboratory documentation must be provided:

a. A1067T

b. A455E

c. D110E

d. D110H

e. D1152H

f. D1270N

g. D579G

h. E193K

i. E56K

j. E831X

k. F1052V

l. F1074L

m. G1069R

n. G1244E

o. G1349D

p. G178R

q. G551D

r. G551S

s. K1060T

t. L206W

u. P67L

v. R1070Q

w. R1070W

x. R117C

y. R117H

z. R347H

aa. R352Q

bb. R74W

cc. S1251N

dd. S1255P

ee. S549N

ff. S549R

gg. S945L

hh. S977F

ii. 2789+5G→A

jj. 3272-26A→G

kk. 3849+10kbC→T

ll. 711+3A→G

3. Member is not homozygous for the F508del mutation on the CFTR gene

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

5. Use is not in combination with lumacaftor-ivacaftor (Orkambi)

6. Member is 2 years of age or older

7. The dose does not exceed:

a. Adults and children ages 6 years and older: 150 mg twice daily

b. Children ages 2 years to less than 6 years:

i. Body weight less than 14 kg: 50 mg twice daily

ii. Body weight 14 kg or greater: 75 mg twice daily

Duration of approval: 6 months

Continuation of ivacaftor (Kalydeco) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue in the past two years 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 ivacaftor AND has been receiving treatment for a minimum of 18 months

3. Ivacaftor is not administered in combination with lumacaftor/ivacaftor (Orkambi)

4. Dose does not exceed:

a. Adults and children ages 6 years and older: 150 mg twice daily

b. Children ages 2 years to less than 6 years:

i. Body weight less than 14 kg: 50 mg twice daily

ii. Body weight 14 kg or greater: 75 mg twice daily

5. Member is 2 years of age or older

Duration of approval: 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:

Dosage Adjustment

Hepatic Impairment:

• The dose of ivacaftor should be reduced to 150 mg once daily for persons with moderate hepatic impairment. Ivacaftor should be used with caution in persons with severe hepatic impairment at a dose of 150 mg once daily or less frequently.

Concomitant use with CYP3A Inhibitors

• When ivacaftor is being co-administered with strong CYP3A inhibitors (e.g., ketoconazole) the dose should be reduced to 150 mg twice-a-week.

• The dose of ivacaftor should be reduced to 150 mg once daily when co-administered with moderate CYP3A inhibitors (e.g., fluconazole). Food containing grapefruit or Seville oranges should be avoided.

Drug Availability:

• Tablets: 150 mg

• Oral granules: Unit-dose packets of 50 mg and 75 mg

PRECAUTIONS:

Transaminase (ALT or AST) Elevations: Elevated transaminases have been reported in persons with CF receiving ivacaftor. Transaminases (ALT and AST) should be assessed prior to initiating ivacaftor, every 3 months during the first year of treatment, and annually thereafter. If a member develops increased transaminase levels, levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted in persons with ALT or AST of greater than 5 times the upper limit of normal (ULN). Following resolution of transaminase elevations, consider the benefits and risks of resuming ivacaftor dosing.

Concomitant Use with CYP3A Inducers: Use of ivacaftor with strong CYP3A inducers, such as rifampin, substantially decreases the exposure of ivacaftor, which may reduce the therapeutic effectiveness of ivacaftor. Therefore, co-administration of ivacaftor with strong CYP3A inducers (e.g., rifampin, St. John’s Wort) is not recommended.

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding:

J8499

Prescription drug, oral, non chemotherapeutic, nos

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

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

DEFINITIONS:

No guideline specific definitions apply.

RELATED GUIDELINES:

Genetic Testing, 05-82000-28
Lumacaftor/Ivacaftor Capsule, 09-J2000-29

OTHER:

None

REFERENCES:

  1. AHFS Drug Information. Bethesda (MD): American Society of Health-System Pharmacists, Inc; 2015 [cited 2015-04-24]. In: STAT!Ref Online Electronic Medical Library [Internet]. Available from: http://online.statref.com/.
  2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2017 [cited 2017-04-24]. Available from: http://www.clinicalpharmacology.com/.
  3. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 2017-04-24]. Available from: http://www.thomsonhc.com/.
  4. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017-04-24]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  5. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 2017-04-24]. Available from: http://clinicaltrials.gov/.
  6. Vertex. Kalydeco (ivacaftor) tablet, film coated; granule. 2017 [cited 2017-03-31]. 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/.

COMMITTEE APPROVAL:

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

GUIDELINE UPDATE INFORMATION:

06/15/12

New Medical Coverage Guideline.

06/15/13

Review and revision to guideline; consisting of revising position statement to exclude coverage for members who are homozygous for the F508del mutation and revising description section; reformatting dosage/administration and precautions section; updating references.

06/15/14

Review and revision to guideline; consisting of revising position statement and updating references.

02/15/15

Review and revision to guideline; consisting of revision of position statement

05/15/15

Revised guideline; consisting of position statement and dosing/administration, references

06/15/15

Review and revision to guideline; consisting of position statement, related guidelines, references

07/15/15

Revision to guideline; updated HCPCS code.

11/01/15

Revision: ICD-9 Codes deleted.

06/15/16

Review and revision to guideline; consisting of revising description, position statement, references.

06/15/17

Review and revision to guideline; consisting of updating references.

07/15/17

Revised position statement to include new mutations per updated FDA indication.

09/15/17

Revised position statement to include new mutations per updated FDA indication.

Date Printed: October 23, 2017: 02:15 AM