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Date Printed: December 18, 2017: 11:43 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-J2000-45

Original Effective Date: 12/15/15

Reviewed: 10/11/17

Revised: 11/15/17

Subject: Sonidegib (Odomzo®) 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  

Previous Version

           

DESCRIPTION:

Sonidegib (Odomzo) was approved by the US Food and Drug Administration (FDA) in July 2015 for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. The drug also was previously granted orphan drug designation for the treatment of medulloblastoma in March 2015. Sonidegib is an oral inhibitor of smoothened (SMO), a transmembrane protein involved in Hedgehog (Hh) signal transduction. It is the second FDA-approved drug targeting the Hh pathway; the first being vismodegib (Erivedge) approved in January 2012. Sonidegib exerts its anti-cancer effects by inhibiting the Hh signaling pathway. The Hh signaling pathway regulates normal cell development, replication, and differentiation and hair growth. Dysregulation of the pathway has been associated with basal cell carcinoma development.

The safety and efficacy of sonidegib was assessed in a multinational, randomized, double-blind, 2-cohort, phase II trial (n=230; the BOLT trial). Patients were randomized (2:1) to receive either sonidegib 800 mg or 200 mg orally, once daily, until disease progression or intolerable toxicity. The objective response rate (ORR) was 58% in patients with locally advanced basal cell carcinoma (laBCC) who received sonidegib 200 mg/day (n=66). There was no evidence of better antitumor activity (ORR) among patients with laBCC randomized to receive sonidegib 800 mg daily. The median progression-free survival time had not been reached in these patients at a median follow-up of 13.9 months. Patients with laBCC were required to have lesions for which radiotherapy was contraindicated or inappropriate (e.g., Gorlin syndrome or limitations because of location of tumor), that had recurred after radiotherapy, that were unresectable or for which surgical resection would result in substantial deformity, or that had recurred after prior surgical resection.

The National Comprehensive Cancer Network (NCCN) guidelines for the treatment of basal cell skin cancer (Version 1.2018) list treatment with a hedgehog pathway inhibitor, in consultation with a multidisciplinary tumor board, as a category 2A option for patients with recurrent nodal disease or distant metastases. Surgery and/or radiation and clinical trials are the other listed options. The NCCN notes that BCCs may develop resistance to hedgehog pathway inhibition. Initial studies have shown no clinical benefit of switching to a different hedgehog pathway inhibitor after disease progression.

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 sonidegib (Odomzo) meets the definition of medical necessity when ALL of the following are met (“1”, “2”, “3”, “4”, and “5”):

1. The member has ANY of the following indications (“a”, “b”, or “c”), AND all associated criteria are met:

a. Metastatic basal cell carcinoma (mBCC) [including basosquamous cell variants]

b. Locally advanced basal cell carcinoma (laBCC) [including basosquamous cell variants] and EITHER of the following (“i” or “ii”):

i. Member’s basal cell carcinoma has recurred with lymph node involvement following previous surgical resection or radiation therapy

ii. Member is not a candidate for both surgical resection AND radiation (reasons for non-candidacy must be provided)

c. Medulloblastoma (orphan indication) and ALL of the following:

i. Member has had an inadequate response, has intolerable adverse effects, or has a contraindication to ALL of the following:

• Craniospinal radiation therapy

• Platinum-based, multi-agent chemotherapy

• Etoposide monotherapy

• Temozolomide monotherapy

2. Sonidegib is NOT being used as neoadjuvant therapy before surgery or radiation

3. The member is not taking another hedgehog pathway inhibitor [e.g., vismodegib (Erivedge)] concurrently with sonidegib

4. The member has not previously experienced disease progression during treatment with another hedgehog pathway inhibitor (e.g., vismodegib) for BCC

5. The member’s dosage of sonidegib does not exceed 200 mg once daily

Approval duration: 1 year

Continuation of sonidegib (Odomzo) meets the definition of medical necessity when ALL of the following are met (“1”, “2”, “3”, and “4”):

1. An authorization or reauthorization for sonidegib has been previously approved by Florida Blue or another health plan in the past 2 years for the treatment of metastatic or locally advanced basal cell carcinoma or medulloblastoma, OR the member previously met ALL indication-specific initiation criteria

2. The member has not experienced disease progression while receiving treatment with sonidegib

3. The member is not taking another hedgehog pathway inhibitor (e.g., vismodegib) concurrently with sonidegib

4. The member’s dosage of sonidegib does not exceed 200 mg daily

Approval duration: 1 year

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

• Sonidegib is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. The recommended dose is 200 mg taken orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal, administered until disease progression or unacceptable toxicity.

Dose Adjustments

• No dose adjustment is recommended for patients with renal impairment

• No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) >ULN or total bilirubin >1.0 to 1.5 times ULN). Use has not been studied in patients with moderate or severe hepatic impairment.

• There was a higher incidence of serious adverse events, Grade 3 and 4 adverse events, and adverse events requiring dose interruption or discontinuation in patients ≥65 years compared with younger patients

• Interrupt therapy for:

o Severe or intolerable musculoskeletal adverse reactions

o First occurrence of serum CK elevation between 2.5 and 10 times upper limit of normal (ULN)

o Recurrent serum CK elevation between 2.5 and 5 times ULN

• Resume sonidegib at 200 mg daily upon resolution of clinical signs and symptoms

• Permanently discontinue therapy for:

o Serum CK elevation greater than 2.5 times ULN with worsening renal function

o Serum CK elevation greater than 10 times ULN

o Recurrent serum CK elevation greater than 5 times ULN

o Recurrent severe or intolerable musculoskeletal adverse reactions

Drug Availability

• 200 mg capsules in 30-count bottles

• Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)

PRECAUTIONS:

Boxed Warning

• Embryo-Fetal Toxicity

o Sonidegib can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. It is embryotoxic, fetotoxic, and teratogenic in animals.

o Verify the pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment with sonidegib and for at least 20 months after the last dose.

o Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with sonidegib and for at least 8 months after the last dose.

Contraindications

• None

Precautions/Warnings

Embryo-fetal Toxicity – see Boxed Warning. Do not breastfeed during treatment with sonidegib and for at least 20 months after the last dose.

Blood donation - advise patients not to donate blood or blood products during treatment with sonidegib and for at least 20 months after the last dose due to the embryo-fetal toxicity

Musculoskeletal Adverse Reactions - musculoskeletal adverse reactions occurred in about two-thirds of patients treated with sonidegib with 13% of reactions reported as Grade 3 or 4. Among patients with Grade 2 or higher CK elevations, the median time to onset was 12.9 weeks (range: 2 to 39 weeks) and the median time to resolution (to ≤ Grade 1) was 12 days (95% CI: 8 to 14 days). Obtain serum creatine kinase (CK) and creatinine levels prior to initiating therapy, periodically during treatment, and as clinically indicated. Obtain serum creatinine and CK levels at least weekly in patients with musculoskeletal adverse reactions with concurrent serum CK elevation greater than 2.5 times ULN until resolution of clinical signs and symptoms. Temporary dose interruption or discontinuation may be required based on the severity of musculoskeletal adverse reactions or CK elevations.

Strong and Moderate CYP3A Inhibitors - avoid concomitant administration of sonidegib with strong and moderate CYP3A inhibitors (e.g., strong – saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole and nefazodone; moderate - atazanavir, diltiazem, fluconazole). If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for less than 14 days and monitor closely for adverse reactions particularly musculoskeletal adverse reactions.

Strong and Moderate CYP3A Inducers - avoid concomitant administration of sonidegib with strong and moderate CYP3A inducers (e.g., carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin and St. John’s Wort)

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

C9399

Unclassified drugs or biologicals (Hospital Outpatient Use ONLY)

J8999

Prescription drug, oral, chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity

C44.01

Basal cell carcinoma of skin of lip

C44.111 – C44.119

Basal cell carcinoma of skin of eyelid, including canthus

C44.211 – C44.219

Basal cell carcinoma of skin of ear and external auricular canal

C44.310

Basal cell carcinoma of skin of unspecified parts of face

C44.311

Basal cell carcinoma of skin of nose

C44.319

Basal cell carcinoma of skin of other parts of face

C44.41

Basal cell carcinoma of skin of scalp and neck

C44.510

Basal cell carcinoma of anal skin

C44.511

Basal cell carcinoma of skin of breast

C44.519

Basal cell carcinoma of skin of other part of trunk

C44.611 – C44.619

Basal cell carcinoma of skin of upper limb, including shoulder

C44.711 – C44.719

Basal cell carcinoma of skin of lower limb, including hip

C44.81

Basal cell carcinoma of overlapping sites of skin

C44.91

Basal cell carcinoma of skin, unspecified

C71.6

Malignant neoplasm of cerebellum

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 review date.

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

DEFINITIONS:

Basal cell carcinoma (BCC) - abnormal, uncontrolled growths or lesions that arise in the skin’s basal cells, which line the deepest layer (i.e., basal cell layer) of the epidermis. BCCs often look like open sores, red patches, pink growths, shiny bumps, or scars, and rarely metastasize beyond the original tumor site. BCC is the most frequently occurring form of all cancers, and the most common skin cancer (8 of 10 skin cancers).

Basosquamous cell (BSC) - is considered an aggressive variant of basal cell carcinoma (BCC) with an increased risk of recurrence and metastases. It shares histologic features of both basal cell and squamous cell carcinoma and is often linked by a transition area. It is also known as metatypical basal cell carcinoma.

Squamous cell carcinoma (SCC) - uncontrolled growth of abnormal cells arising in the squamous cells, which compose most of the skin’s upper layers (the epidermis). SCCs often look like scaly red patches, open sores, elevated growths with a central depression, or warts; they may crust or bleed. About 2 of 10 skin cancers are SCC. SCCs are more likely to grow into deeper layers of skin and spread to other parts of the body than BCC, but this is still uncommon.

RELATED GUIDELINES:

Mohs’ Micrographic Surgery - 02-10000-03

Vismodegib (Erivedge), 09-J1000-66

OTHER:

None

REFERENCES:

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. Available at: www.clinicalpharmacilogy-ip.com. Accessed 9/20/17.
  2. Danial C, Sarin KY, Oro AE, et al. An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib. Clin Cancer Res. 2016 Mar 15;22(6):1325-9.
  3. Geeraert P, Williams JS, Brownell I. Targeting the hedgehog pathway to treat basal cell carcinoma. J Drugs Dermatol. 2013 May;12(5):519-23.
  4. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 9/20/17.
  5. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol. 2015 Jun;16(6):716-28
  6. National Comprehensive Cancer Network. Cancer Guidelines. Cancer Guidelines and Drugs and Biologics Compendium. Accessed 9/20/17.
  7. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2018. Basal Cell Skin Cancer. Available at http://www.nccn.org/professionals/physician_gls/PDF/nmsc.pdf. Accessed 9/20/17.
  8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Version 1.2017. Central Nervous System Cancers. Available at https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. Accessed 9/20/17.
  9. Odomzo (sonidegib) [package insert]. Novartis Pharmaceuticals Corporation: East Hanover, NJ. May 2016.
  10. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2017 [cited 2017 Sept 20]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.
  11. Rodon J, Tawbi HA, Thomas AL, et al. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res. 2014 Apr 1;20(7):1900-9.
  12. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012 Jun 7;366 (23):2171-9.
  13. Shou Y, Robinson DM, Amakye DD, et al. A five-gene hedgehog signature developed as a patient preselection tool for hedgehog inhibitor therapy in medulloblastoma. Clin Cancer Res. 2015 Feb 1;21(3):585-93.
  14. Silapunt S, Chen L, Migden MR. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness. Ther Adv Med Oncol. 2016 Sep;8(5):375-82.
  15. Sofen H, Gross KG, Goldberg LH, et al. A phase II, multicenter, open-label, 3-cohort trial evaluating the efficacy and safety of vismodegib in operable basal cell carcinoma. J Am Acad Dermatol. 2015 Jul;73(1):99-105.e1

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 10/11/17.

GUIDELINE UPDATE INFORMATION:

12/15/15

New Medical Coverage Guideline.

11/15/16

Review and revision to guideline consisting of updating the description, position statement, dosage/administration, precautions, billing/coding, definitions, related guidelines, and references.

11/15/17

Review and revision to guideline consisting of updating the description, position statement, and references.

Date Printed: December 18, 2017: 11:43 AM