Pharmacy Benefit Updates

DATE: September 12, 2014 TO: All BMC HealthNet Plan Provide rs

PRODUCT: MassHealth Commonwealth Care Commercial

ConnectorCare/Qualified Health Plan

Effective Date: November 12, 2014

Policy Changes The following clinical policies will be updated:

• Antineoplastic Agents (9.041) • Botulinum Toxin (9.106) • Hepatitis C Medications (9.123) • Growth Hormone and IGF-1 (9.125)

Prior Authorization Program The following drugs will be added to the Prior Authorization Program • Caprelsa® • Giazo® • Signifor® • Copaxone® 40mg/ml • Imbruvica™ • Sylvant® • Cyramza™ • Marqibo® • Tafinlar® • Folotyn® • Mekinist™ • Zelboraf® • Fulyzaq® • Procysbi™ • Zykadia™ • Gattex®

Please note the restrictions listed for these policies/medications may differ by plan product. Please visit the Pharmacy section of bmchp.org for complete policies and forms.

Two Copley Place • Suite 600 • Boston, MA 02116 • WWW.BMCHP.ORG

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Clinical Coverage Guidelines Antineoplastic Agents

BMCHP refers to Boston Medical Center HealthNet Plan in Massachusetts and Well Sense Health Plan in New Hampshire. Boston Medical Center HealthNet Plan and Well Sense Health Plan are trade names used by Boston Medical Center Health Plan, Inc.

BMC HealthNet Plan Well Sense Health Plan

Policy Applicability MassHealth New Hampshire Medicaid Commonwealth Care Commercial ConnectorCare/Qualified Health Plan (QHP)

Effective Date: 11/12/2014 Policy Number: 9.041 Policy Effective Date: 10/01/2013 Last Review Date: 07/10/2014 Approved by: Pharmacy and Therapeutics Committee Policy Owner/Title: Pharmacy Services

Summary BMC HealthNet Plan will authorize coverage of the following antineoplastic agents when appropriate criteria are met.

Description of Item or Service Antineoplastic agents are used in the treatment of various oncology diagnoses. New antineoplastic agents are entering the market monthly, reflected in the increasingly vast array of treatment options for patients with

This guideline provides information on BMC HealthNet Plan clinical criteria and claims adjudication processing guidelines. The use of this guideline is not a guarantee of payment and will not determine how a specific claim(s) will be paid. Reimbursement is based on member benefits and eligibility, medical necessity review, where applicable, coordination of benefits, adherence to Plan policies, clinical coding criteria, and the BMC HealthNet Plan agreement with the rendering or dispensing provider. Reimbursement policies may be amended at BMC HealthNet Plan’s discretion. BMC HealthNet Plan will always use the most recent CPT and HCPCS coding guidelines. All Plan policies are developed in accordance with state, federal and accrediting organization guidelines and requirements, including NCQA.

BMC HealthNet Plan – Antineoplastic Agents

1 of 8 oncology diagnoses. These agents differ in their mechanism of action, FDA-approved indications, off-label uses, route of administration, drug interactions and adverse effects.

Clinical Guideline Statement Policy Applicability by Product Medication BMC Health Plan MassHealth CWC COMM QHP AdcetrisTM X X X X Caprelsa X X X X Cyramza X X X X Erwinaze X X X X Gilotrif X X X X Icusig X X X X Imbruvica X X X X Inlyta X X X X Kadcyla X X X X Kyprolis X X X X Marqibo X X X X Mekinist X X X X Pomalyst X X X X Stivarga X X X X Sylvant X X X X Synribo X X X X Tafinlar X X X X Zaltrap X X X X Zelboraf X X X X Zykadia X X X X NF=non-formulary

BMC HealthNet Plan may authorize coverage of the following antineoplastic agents for members meeting the following criteria:

Prior Authorization – (Duration of Approval – Maximum of 1 year)

A prior authorization request will be required for all prescriptions for the following antineoplastic agents. These requests will be approved when the following criteria are met:

Medication Prior Authorization Criteria

BMC HealthNet Plan – Antineoplastic Agents

2 of 8 All requests for the antineoplastic agents listed in the table below will require the following documentation: • The quantity of medication prescribed is consistent with dosing listed in manufacturer package labeling for the prescribed indication • The prescriber is a specialist appropriate to the disease state being treated (e.g. oncologist, hematologist, etc). • For non-FDA approved indications, the member must have a diagnosis consistent with recommended usage of the medication as listed in the NCCN Compendia AND has had an inadequate response, contraindication or adverse effect to standard treatment options if applicable. AdcetrisTM Documentation of the following: (brentuximab injection) 1. A diagnosis of Hodgkin lymphoma; AND An inadequate response to at least 2 prior chemotherapy regimens (in patients ineligible for stem cell transplant) or a treatment failure of stem cell transplant; OR

2. A diagnosis of systemic anaplastic large cell lymphoma (sALCL); AND An inadequate response to at least 1 prior chemotherapy regimen ErwinazeTM Documentation of the following: (erwinia asparaginase 1. A diagnosis of acute lymphoblastic leukemia (ALL); AND injection) 2. Member is currently receiving treatment with other chemotherapy; AND 3. There is a hypersensitivity to E. coli-derived asparaginase Inlyta® Documentation of the following: (axitinib tablet) 1. A diagnosis of advanced renal cell cancer (RCC); AND 2. An inadequate response to 1 prior treatment

Kyprolis® Documentation of the following: (carfilzomib injection) 1. A diagnosis of multiple myeloma; AND 2. An inadequate response to at least 2 prior complete treatment regimens including a proteasome inhibitor and immunomodulator Zaltrap® Documentation of the following: (ziv-aflibercept injection) 1. A diagnosis of metastatic colorectal cancer; AND 2. An inadequate response to an oxiplatin-based regimen; AND 3. The medication will be used in combination with fluorouracil, leucovorin and irinotecan [FOLFIRI] or irinotecan alone Bosulif® Documentation of the following: (bosutinib tablet) 1. A diagnosis of chronic, accelerated or blast phase Philadelphia chromosome- positive (Ph+) chronic myelogenous leukemia (CML); AND 2. An inadequate response or intolerance to any prior therapy

BMC HealthNet Plan – Antineoplastic Agents

3 of 8 Stivarga® Documentation of the following: (regorafenib tablet) 1. A diagnosis of metastatic colorectal cancer; AND Previous treatment with fluoropyrimidine-, oxiplatin-, and irinotecan-based therapy, anti-VEGF therapy, or anti-EGFR therapy; OR

2. A diagnosis of locally-advanced, unresectable, or metastatic gastrointestinal stromal tumor (GIST); AND Previous treatment with imatinib and sunitinib SynriboTM Documentation of the following: (omacetaxine injection) 1. A diagnosis of chronic or accelerated phase chronic myelogenous leukemia (CML); AND 2. Resistance or intolerance to 2 or more tyrosine kinase inhibitors IclusigTM Documentation of the following: (ponatinib tablet) 1. A diagnosis of chronic, accelerated, or blast phase chronic myelogenous leukemia (CML) OR Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL); AND 2. Resistance or intolerance to prior tyrosine kinase inhibitor therapy OR a diagnosis of CML with documented T3151 mutation Pomalyst® Documentation of the following: (pomalidomide capsule) 1. A diagnosis of multiple myeloma; AND 2. An inadequate response to at least 2 prior therapies including lenalidomide and bortezomib KadcylaTM Documentation of the following: (ado-trastuzumab injection) 1. A diagnosis of HER2-positive, metastatic breast cancer; AND 2. An inadequate response to a trastuzumab-based regimen

MekinistTM Documentation of the following: (trametinib tablet) 1. A diagnosis of metastatic or unresectable melanoma; AND 2. Confirmation of BRAF V600E or BRAF V600K mutation; AND 3. Not being used as single agent if member has prior BRAF-inhibitor therapy

BMC HealthNet Plan – Antineoplastic Agents

4 of 8 Tafinlar® Documentation of the following: (dabrafenib capsule) 1. Being used as a single agent; AND A diagnosis of unresectable or metastatic melanoma; AND Confirmation of BRAF 600E mutation; AND BRAF wild-type cells are not present; OR

2. Being used in combination with trametinib; AND A diagnosis of unresectable or metastatic melanoma; AND Confirmation of BRAF 600E or V600K mutations; AND BRAF wild-type cells are not present

Documentation of the following: Imbruvica™(Ibrutinib 1. Diagnosis of mantle cell lymphoma (MCL); AND capsule) An inadequate response to at least one prior therapy; OR

2. Diagnosis of chronic lymphocytic leukemia (CLL); AND An inadequate response to at least one prior therapy

Folotyn® Documentation of the following: (pralatrexate injection) 1. Diagnosis of relapsed or refractory T-cell lymphoma (peripheral or cutaneous); AND 2. Member has been supplemented with vitamin B12 1mg IM within 10 weeks prior to starting therapy; AND 3. Member has been supplemented with folic acid 1-1.25 mg orally once daily beginning 10 days before starting therapy; AND 4. There is a plan for the member to take vitamin B12 1 mg IM every 8-10 weeks AND folic acid 1-1.25 mg orally once daily during full course of therapy

Zelboraf® Documentation of the following: (vemurafenib tablet) 1. Diagnosis of unresectable or metastatic melanoma; AND 2. Confirmation of BRAFV600E mutation; AND 3. Member does not have wild-type BRAF melanoma Caprelsa® Documentation of the following: (vandetanib tablet) 1. Diagnosis of metastatic or unresectable medullary thyroid cancer; AND 2. Cancer is symptomatic OR progressive

BMC HealthNet Plan – Antineoplastic Agents

5 of 8 CyramzaTM Documentation of the following: (ramucirumab injection) 1. Diagnosis of advanced or metastatic gastric or gastroesophageal junction adenocarcinoma; AND 2. Disease progression on or following fluoropyrimidine or platinum-containing chemotherapy SylvantTM Documentation of the following: (siltuximab injection) 1. Diagnosis of multicentric Castleman’s disease; AND 2. Member is HIV negative; AND 3. Member is herpesvirus-8 (HHV-8) negative ZykadiaTM Documentation of the following: (ceritinib capsule) 1. Diagnosis of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC); AND 2. Member has progressed on or is intolerant to crizotinib Marqibo® Documentation of the following: (vincristine sulfate liposome injection) 1. Diagnosis of Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL); AND 2. Member is in ≥ second relapse OR the disease has progressed following ≥ 2 anti- leukemia therapies

Limitations BMC HealthNet Plan will not approve coverage of the antineoplastic agents listed above in the following instances:

• When the above criteria are not met.

Clinical Background Information and References 1. AdcetrisTM [package insert]. Bothell (WA): Seattle Genetics; Jan 2012. 2. ErwinazeTM [package insert]. Langhome (PA): EUSA Pharma, Inc.; Nov 2011. 3. Inlyta® [package insert]. New York (NY): Pfizer Inc.; Jan 2012. 4. Kyprolis® [package insert]. San Francisco (CA): Onyx Pharmaceuticals, Inc.; July 2012. 5. Zaltrap® [package insert]. Bridgewater (NJ): Sanofi-Aventis U.S. LLC; Aug 2012. 6. Bosulif® [package insert]. New York (NY): Pfizer Inc.; Apr 2013. 7. Stivarga® [package insert]. Wayne (NJ): Bayer HealthCare Pharmaceuticals Inc.; Feb 2013. 8. SynriboTM [package insert]. North Wales (PA): Teva Pharmaceuticals USA, Inc.; Oct 2012. 9. IclusigTM [package insert]. Cambridge (MA): ARIAD Pharmaceuticals, Inc.; Dec 2012.

BMC HealthNet Plan – Antineoplastic Agents

6 of 8 10. Pomalyst® [package insert]. Summit (NJ): Celgene Corporation; Feb 2013. 11. KadcylaTM [package insert]. San Francisco (CA): Genentech, Inc.; May 2013. 12. NCCN Drugs & Biologics Compendium™ [database on the internet]. Fort Washington (PA): National Comprehensive Cancer Network; Updated periodically [cited 2014 Jun 24]. Available from http://www.nccn.org. 13. MekinistTM [package insert]. Triangle Park (NC): GlaxoSmithKline; Jan 2014. 14. Tafinlar® (package insert). Triangle Park (NC): GlaxoSmithKline; Jan 2014. 15. Gilotrif® (package insert). Ridgefield (CT): Boehringer Ingelheim; Apr 2014. 16. ImbruvicaTM (package insert). Sunnyvale (CA): Pharmacyclics; Feb 2014. 17. Folotyn® (package insert). Westminster (CO): Allos Therapeutics; Jan 2011. 18. Zelboraf® (package insert). San Francisco (CA): Genentech; Mar 2014. 19. Caprelsa® (package insert). Wilmington (DE): AstraZeneca; Mar 2014. 20. CyramzaTM (package insert). Indianapolis (IN): Eli Lilly and Company; Apr 2014. 21. SylvantTM (package insert). Horsham (PA): Janssen; Apr 2014. 22. ZykadiaTM (package insert). East Hanover (NJ): Novartis; Apr 2014. 23. Marqibo®(package insert). South San Francisco (CA): Talon; Oct 2012.

Policy History

Effective Date: 10/01/2013

Review Dates Dates of Review/Revision: 12/13/2013 – Policy applied to ConnectorCare/Qualified Health Plan

Last Review/Revision Date: 7/10/2014 – P&T Annual Review, added criteria for Mekinist, Tafinlar, Folotyn, Imbruvica, Zelboraf, Caprelsa, Cyramza, Sylvant, Zykadia, Marqibo; updated criteria for Zaltrap and Kadcyla; added Icusig, Kadcyla and Pomalyst to QHP formulary

Next Review Date: 07/09/2015

Approval Dates Regulatory Approval: N/A Internal Approval: Initial approval by Pharmacy & Therapeutics Committee – July 11, 2013 Authorizing Entity: P&T Committee

Important Notes:

BMC HealthNet Plan – Antineoplastic Agents

7 of 8 review of clinical studies published in peer-reviewed medical literature. Even though this policy may indicate that a particular service or supply is considered covered or not covered, this conclusion is not based upon the terms of a member’s particular benefit plan. Each benefit plan contains its own specific provisions for coverage and exclusions. Not all services that are determined to be medically necessary will necessarily be covered services under the terms of a member’s benefit plan. Members and their providers need to consult the applicable benefit plan document (e.g., Evidence of Coverage) to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between this medical policy and the benefit plan document, the provisions of the benefit plan document will govern. In addition, this policy and the benefit plan document are subject to applicable state and federal laws that may mandate coverage for certain services and supplies.

BMC HealthNet Plan – Antineoplastic Agents

8 of 8

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Clinical Coverage Guidelines Botulinum Toxins - Botox®, Dysport®, Myobloc®, Xeomin®

BMC HealthNet Plan Well Sense Health Plan

Policy Applicability MassHealth New Hampshire Medicaid Commonwealth Care Commercial ConnectorCare/Qualified Health Plan (QHP)

Effective Date: 11/12/2014 Policy Number: 9.106 Policy Effective Date: 07/10/2013 Last Review Date: 07/10/2014 Approved by: Pharmacy and Therapeutics Committee Policy Owner/Title: Pharmacy Services

Summary BMC HealthNet Plan may authorize coverage of Botox®, Dysport®, Myobloc®, and Xeomin® when appropriate criteria are met.

Description of Item or Service Botox® (onabotulinumtoxinA), Dysport® (abotulinumtoxinA), Myobloc® (rimabotulinumtoxinB), and Xeomin® (incobotulinumtoxin A) are neurotoxins produced by clostridium botulinum, a spore-forming anaerobic

BMC HealthNet Plan – Botulinum Toxin

1 of 8 bacillus. These neurotoxins exert their effect by preventing the release of acetylcholine from the presynaptic portion of the neuron into the neuromuscular junction producing a state of muscle denervation and inactivation which persists until new fibrils grow from the nerve and form junction plates on new areas of the muscle cell walls. Current FDA approved indications for onabotulinumtoxinA, abotulinumtoxinA, and rimabotulinumtoxinB are included in the table below:

FDA approved indications for botulinum type A and type B Product FDA Approved Indications Onabotulinumtoxin A • Strabismus and Blepharospasm associated with dystonia in ® (Botox ) patients >12 years of age • Primary axillary hyperhidrosis in patients > 18 years of age, when topical agents have failed • Prophylaxis of chronic migraine in patients > 18 years of age • Spasmodic Torticollis (cervical dystonia) in patients >16 years of age • Upper limb spasticity in patients > 18 years of age • Detrusor overactivity associated with a neurologic condition in patients > 18 years of age, when anticholinergic agents have failed • Overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency in patients > 18 years of age, when anticholinergic agents have failed • Glabellar Lines (wrinkles)* Abotulinumtoxin A • Cervical dystonia ® (Dysport ) • Glabellar lines (wrinkles)* incobotulinumtoxin A • Blepharospasm in adult patients ® (Xeomin ) • Cervical dystonia in adult patients • Glabellar lines (wrinkles)* Rimabotulinumtoxin B • Spasmodic Torticollis (cervical dystonia) in patients 16 years of ® (Myobloc ) age or older *BMCHP does not provide coverage of medications for cosmetic indications.

In addition to the FDA indications listed above, botulinum toxins have commonly been used for several off- label indications, and new indications continue to emerge. Botulinum toxins are generally used for these indications as a second line therapy after conventional treatments have failed. Non-FDA approved indications with evidence of efficacy for botulinum toxins are limited to onabotulinumtoxinA and include the following:

Non-FDA Approved Indications for onabotulinumtoxinA

• Achalasia

BMC HealthNet Plan – Botulinum Toxin

2 of 8 • Chronic anal fissure • Limb spasticity (secondary to Cerebral Palsy, Stroke, Multiple Sclerosis, etc) • Hemifacial Spasm • Oromandibular Dystonia • Spasmodic dysphonia (laryngeal dystonia) • Focal Upper Limb Dystonias (i.e. organic writer’s cramp) • Palmar Hyperhidrosis • Essential hand tremor

The use of botulinum toxin for non-FDA approved indications not listed above has resulted in conflicting evidence in regard to efficacy. Currently, there is no definitive data to suggest treatment with botulinum toxin will confer any benefit for the management of those conditions. Therefore, BMCHP has limited the use of botulinum toxin therapy to FDA-approved indications and specific non-FDA approved indications listed above.

Clinical Guideline Statement Policy Applicability by Product BMC HealthNet Plan Medication MassHealth CWC COMM QHP Botox X X X X Dysport X X X X Myobloc X X X X Xeomin X X X X

BMC HealthNet Plan may approve coverage of Botox®, Dysport®, Myobloc®, and Xeomin® for members meeting the following criteria:

Prior Authorization – (Duration of Approval – Maximum of 6 month for the indication of chronic migraine prophylaxis (Botox only®)*; Maximum of 1 year for all other indications)

A prior authorization request will be required for all prescriptions for Botox®, Dysport®, Myobloc®, and Xeomin®. These requests will be approved when the following criteria are met:

Initial therapy

Botox®

1. Documentation of one of the following diagnoses: • Cervical dystonia or Spasmodic torticollis and age is 16 years or older • Blepharospasm and age is 12 years or older

BMC HealthNet Plan – Botulinum Toxin

3 of 8 • Strabismus and age is 12 years or older • Primary Axillary Hyperhidrosis, despite trial of topical agents and age is 18 years or older • Upper limb spasticity and age is 18 years or older; OR 2. A diagnosis of urinary incontinence (detrusor overactivity) associated with a neurologic condition (e.g spinal cord injury, multiple sclerosis) or overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and frequency; and

An inadequate response, intolerance or a contraindication to a trial of at least 2 anticholinergic agents; OR 3. A diagnosis of chronic migraines with more than 15 migraine days per month and headaches lasting 4 hours a day or longer; and

Diagnosis has been confirmed by a neurologist consult; and

An inadequate response (persistent 15 migraine headache days per month) or intolerance to at least a 30-day trial each of one migraine prophylaxis medication at the maximum tolerated dose from at least three of the therapeutic classes below: • Beta blockers: metoprolol, propranolol, timolol, atenolol, nadolol, nebivolol, pindolol • Antidepressants: amitriptyline, venlafaxine • Anticonvulsants: carbamazepine, divalproex, valproic acid, topiramate • Alpha adrenagic agonists: clonidine or guanfacine • ACE-inhibitors: lisinopril • Angiotensin receptor blockers: candesartan • Triptans: frovatriptan, naratriptan, zolmitriptan for short-term menstrually associated migraine (MAMs) prevention

*Recommended dose= 155U/12 weeks

OR 4. Documentation of the following non-FDA approved indications: • Achalasia • Chronic anal fissure • Limb spasticity (secondary to Cerebral Palsy, Stroke, Multiple Sclerosis, etc) • Hemifacial Spasm • Oromandibular Dystonia • Spasmodic dysphonia (laryngeal dystonia) • Focal Upper Limb Dystonias (i.e. organic writer’s cramp)

BMC HealthNet Plan – Botulinum Toxin

4 of 8 • Palmar Hyperhidrosis • Essential hand tremor AND An inadequate clinical response and/or intolerance to currently accepted therapeutic options recommended by a nationally recognized entity specific to the disease for which the member is being treated (or as determined by a review of the available clinical evidence if recommendations from a nationally recognized entity have not been published)

Dysport®

1. Documentation of a diagnosis of cervical dystonia and age is 18 years or older.

Myobloc®

1. Documentation of a diagnosis of cervical dystonia and age is 16 years or older OR 2. An inadequate response to onabotulinumtoxinA (Botox®) for an indication that was previously approved by the Plan due to development of resistance.

Xeomin®

1. Documentation of a diagnosis of blepharospasm or cervical dystonia and age is 18 years or older; and An inadequate response, intolerance, or contraindication to a trial of Botox®

Continuation of Therapy

Prior Authorization is required for all prescriptions for continued treatment beyond the initial approval duration. These requests will be approved when the following criteria are met:

1. Documentation of clinically significant reduction in symptom severity/ frequency, or improvement of functional ability.

BMC HealthNet Plan – Botulinum Toxin

5 of 8 Applicable HCPCs codes

Drug Name HCPCs code

Botox® (onabotulinumtoxin A) J0585

Dyport® (abotulinumtoxin A) J0586

Myobloc® (rimabotulinumtoxin B) J0587

Xeomin® (incobotulinumtoxin A) J0588

Limitations BMC HealthNet Plan will not approve coverage of Botox®, Dysport®, Xeomin®, or Myobloc® in the following instances:

1. When the criteria above has not been met. 2. When used for treatment of cosmetic indications (i.e. wrinkles).

Clinical Background Information and References 1. Simpson DM, Gracies J-M, Graham JM, et al. Assessment: Botulinum neurotoxin for the treatment of spasticity (an evidence-based review): Report of the Therapeutics and Technology Assessment subcommittee of the American Academy on Neurology; Neurology 2008; 70;1691-1698. 2. Simpson DM, Blitzer A, Brashear A., et al. Assessment: Botulinum neurotoxin for the treatment of movement disorders (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology; Neurology 2008;70;1699-1706. 3. Naumann M, So CE, Argoff M., et al. Assessment: Botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology; Neurology 2008; 70;1707-1714. 4. Botulinum toxin type a: Drug Information. Lexi-comp, Inc. UptoDate®, Accessed July 2014; available from http://uptodate.com. 5. Botox® (onabotulinumtoxin A) prescribing information. Allergan, Inc. Irvine, CA 92612. August 2011. revised February 2014 6. Xeomin® (incobotulinumtoxin A) prescribing information. Merz pharmaceuticals, LLC. Greensboro, NC 27410. August 2010, revised April 2014 7. Myobloc® (rimabotulinumtoxin B) prescribing information. Solstice Neurosciences, Inc. South San Francisco, CA 94080. May 2010. 8. Dysport® (abobotulinumtoxin A) prescribing information. Tercica, Inc., a subsidiary of the Ipsen Group. Brisbane, CA 94005. April 2010, revised September 2013

BMC HealthNet Plan – Botulinum Toxin

6 of 8 9. Silberstein SD, Holland S, Freitag F, Dodick DW, Argoff C, Ashman E. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012 Apr 24;78(17):1337-45. Accessed via http://www.guideline.gov/content.aspx?id=36898. July 2014 10. Hayes Medical Technology Directory. Botulinum Toxin Treatment for Migraine Headache. Winifred Hayes, Inc. September 22, 2011. Updated October 15, 2013

Policy History

Effective Date: 07/10/2003

Review Dates Dates of Review/Revision: 9/9/2004 – Clarified criteria for diagnosis of Primary Axillary Hyperhidrosis, and added migraine prevention as approvable indication. 3/10/2005 – Initial approval of 3 months, added renewal criteria. 9/27/2007 – P&T Annual Review, policy renamed from “Cosmetic Use of Drug”, added criteria for Myobloc, removed indications for achalasia, migraine prevention, strabismus, cervical dystonia for botulinum toxin type A, removed cosmetic criteria pertaining to Sculptra® and acne medications (ref. Acne Therapy clinical guidelines), removed approval length and renewal criteria. 09/25/2008 – P&T Annual Review, approvable non-FDA approved indications updated 09/10/2009 – P&T Annual Review, Dysport® added to criteria, new generic names for botulinum toxins added. 07/08/2010 – P&T Annual Review, no changes required 01/13/2010 – Policy Update, added criteria for Xeomin®, added new indication of migraine prophylaxis for Botox® 07/14/2011 – P&T Annual Review, policy applied to Commercial 07/12/2012 – P&T Annual Review, criteria added for Botox for detrusor overactivity associated with a neurologic condition; remove requirement of triptan trials for Botox for migraine prophylaxis; added requirement of one additional prophylactic trial, modified continuation criteria 07/11/2013 – P&T Annual Review, criteria added for Botox for overactive bladder, FDA approved indications updated, modified continuation criteria 12/13/2013 – Policy applied to ConnectorCare/Qualified Health Plan (QHP)

Last Review/Revision Date: 07/10/2014 – P&T Annual Review, criteria for Xeomin for cervical dystonia modified to include Botox trial, updated list of acceptable preventative migraine medications required for Botox approval

Next Review Date: 07/09/2015

Approval Dates Regulatory Approval: N/A Internal Approval: Initial approval by Pharmacy & Therapeutics Committee – July 10, 2003

BMC HealthNet Plan – Botulinum Toxin

7 of 8 Authorizing Entity: P&T Committee

Important Notes:

 Not all services are covered for all products or employer groups. This medical policy expresses the Plan's determination of whether certain services or supplies are medically necessary, experimental or investigational or cosmetic. The Plan has reached these conclusions based upon the regulatory status of the technology and a review of clinical studies published in peer-reviewed medical literature. Even though this policy may indicate that a particular service or supply is considered covered or not covered, this conclusion is not based upon the terms of a member’s particular benefit plan. Each benefit plan contains its own specific provisions for coverage and exclusions. Not all services that are determined to be medically necessary will necessarily be covered services under the terms of a member’s benefit plan. Members and their providers need to consult the applicable benefit plan document (e.g., Evidence of Coverage) to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between this medical policy and the benefit plan document, the provisions of the benefit plan document will govern. In addition, this policy and the benefit plan document are subject to applicable state and federal laws that may mandate coverage for certain services and supplies.

BMC HealthNet Plan – Botulinum Toxin

8 of 8

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Clinical Coverage Guidelines Hepatitis C

BMC HealthNet Plan Well Sense Health Plan

Policy Applicability MassHealth New Hampshire Medicaid Commonwealth Care Commercial ConnectorCare/Qualified Health Plan (QHP)

Effective Date: 11/12/2014 Policy Number: 9.123 Policy Effective Date: 09/08/2003 Last Review Date: 07/10/2014 Approved by: Pharmacy and Therapeutics Committee Policy Owner/Title: Pharmacy Services

Summary BMC HealthNet Plan may authorize coverage of specific medications used in the treatment of Hepatitis C when appropriate criteria are met.

Description of Item or Service Chronic Hepatitis C

BMC HealthNet Plan – Hepatitis C

1 of 17 Treatment is indicated for patients with chronic hepatitis C, circulating HCVRNA who have elevated aminotransferase levels, evidence of moderate to severe hepatitis (e.g. METAVIR score exhibiting bridging fibrosis or cirrhosis), compensated liver disease, and are able to adhere to their treatment regimen. It is also appropriate for patients with milder disease (e.g. milder histologic changes, normal aminotransferase) to be offered therapy when it is determined that there is an urgency for treatment initiation. For patients who choose to defer therapy, periodic laboratory and histologic monitoring should be arranged by their treating physician.

The previous standard of care for treatment of chronic hepatitis C consisted of a combination of injectable peginterferon (weekly) and oral ribavirin therapy (daily). This regimen is no longer recommended by the American Association for the Study of Liver Diseases (AASLD) and the Infectious. Diseases Society of America (IDSA) due to the low sustained virologic response (SVR) compared with newer regimens that include the use of a Direct Acting Antivirals (DAAs).

The use of a DAA in combination with peginterferon and/or ribavirin is known to be a more effective regimen than peginterferon/ribavirin alone. DAAs target the HCV life cycle directly, and they are FDA-approved for the treatment of chronic hepatitis C in patients with compensated liver disease who are treatment naïve or have failed previous therapy. Victrelis® (boceprevir) and Incivek® (telaprevir) are first generation DAAs and have SVR rates of up to 75% in clinical trials compared to approximately 40% with peginterferon/ribavirin therapy alone. Incivek® carries a Black Box warning regarding serious skin reactions including Stevens Johnson Syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal Necrolysis. Fatal cases have been reported in patients who continued to receive Incivek® combination treatment after serious skin reaction was identified. If skin reaction is identified, the entire regimen of Incivek®, peginterferon and ribavirin should be discontinued immediately and the patient promptly referred for urgent medical care.

The second generation DAAs include OlysioTM (simeprevir) and Sovaldi® (sofosbuvir). OlysioTM is approved by the FDA for the treatment of chronic hepatitis C genotype 1 in adult patients with compensated liver disease, including cirrhosis. Use of OlysioTM in patients with moderate to severe hepatic impairment is not recommended. OlysioTM is an HCV NS3/4A protease inhibitor and is approved in combination with interferon and ribavirin. Screening patients with genotype 1a at baseline for the presence of the NS3 Q80K polymorphism is strongly recommended when OlysioTM is used in combination with interferon and ribavirin. Alternative regimens should be considered for patients that are Q80K polymorphism positive. OlysioTM has not been studied in patients who have had a null response to regimens with a protease inhibitor (e.g, boceprevir, telaprevir). As a result, OlysioTM is not recommended in patients whose hepatitis C was previously treated with a protease inhibitor.

Sovaldi® is a nucleotide polymerase inhibitor that targets HCV NS5B RNA-dependent RNA polymerase. It disrupts the viral replication process and has been shown to have activity against all hepatitis C genotypes, including those resistant to protease inhibitors. Sovaldi® is approved in combination with peginterferon and ribavirin for the treatment of genotypes 1 and 4. It is also approved as a dual regimen with ribavirin for

BMC HealthNet Plan – Hepatitis C

2 of 17 genotypes 2 and 3, and for all chronic hepatitis C genotypes with hepatocellular carcinoma meeting Milan criteria (awaiting liver transplantation). Sovaldi® can also be used in patients with HCV/HIV-1 co-infection.

The addition of a second generation DAA to peginterferon/ribavirin therapy provides a treatment option with an SVR greater than 90%. It also potentially shortens treatment duration from 48 weeks traditionally down to 12 weeks, depending on the choice of the DAA agent and the patient’s HCV genotype. Currently, AALSD guidelines recommend regimens with a second generation DAA as the first therapy choice for chronic hepatitis C.

With the exception of a regimen using Sovaldi®, monitoring of HCVRNA levels during the treatment course should be done to determine whether the patient has experienced an early virologic response (EVR), which serves as a predictor of SVR. It is recommended that peginterferon/ribavirin therapy be discontinued in the absence of an EVR, because the likelihood of an SVR in this circumstance is very low (0 – 3%). In addition, patients on triple drug therapy including Incivek®, OlysioTM, or Victrelis®, require HCV-RNA monitoring to determine treatment futility. It is recommended that a treatment regimen with Incivek® be discontinued in patients with HCV-RNA levels ≥ 1000 IU/mL at treatment week 4 or 12 or if there is confirmed detectable HCV- RNA at treatment week 24. The Victrelis® treatment regimen differs slightly in that discontinuation of therapy is recommended in patients who have HCV-RNA levels ≥ 100 IU/mL at treatment week 12 or confirmed detectable HCV-RNA at treatment week 12. For OlysioTM, treatment is to be stopped if HCV RNA > 25IU/ml at week 4,12 or 24; AASLD guidelines recommend week 4 as the turning point to determine the appropriateness of completing 24-week treatment for treatment naïve patients.

Data on treatment with the combination of Sovaldi® and OlysioTM used in genotype 1 has shown an encouraging SVR of 90% on average. This dual regimen has not been approved by the FDA but the AASLD guidelines do recommend Sovaldi® and OlysioTM with or without ribavirin in patients with genotype 1 who are considered interferon ineligible (see table 1 for definition) and have not previously failed treatment with a protease inhibitor.

Table 1: Definition of “interferon-ineligible”9 Interferon Ineligible • Intolerance to interferon • Autoimmune hepatitis and other autoimmune disorders • Hypersensitivity to pegylated interferon or any of its components • Decompensated hepatic disease • Major uncontrolled depressive illness • Baseline neutrophil count < 1500/µL, baseline platelet count below 90,000/µL, or baseline hemoglobin < 10 g/dL • History of preexisting cardiac disease

BMC HealthNet Plan – Hepatitis C

3 of 17

Similarly, the use of Sovaldi®and ribavirin without peginterferon is approved by the FDA, although the study group is small. In light of safer and more effective interferon-free treatment options being available in the near future, AASLD/IDSA has recommended reserving the above regimen for patients in immediate need for chronic hepatitis C treatment.

Table 2: Recommended Treatment Duration – Incivek® Treatment naïve and prior relapse patients HCV-RNA Triple Therapy Dual Therapy Total Treatment Duration Undetectable at weeks 4 and 12 First 12 weeks Additional 12 weeks 24 weeks Detectable (≤ 1000 IU/mL) at weeks 4 First 12 weeks Additional 36 weeks 48 weeks and/or 12 Prior partial and null responder patients All patients First 12 weeks Additional 36 weeks 48 weeks Note: treatment-naïve patients with cirrhosis who have undetectable HCV-RNA at weeks 4 and 12 may benefit from an additional 36 weeks of peginterferon/ribavirin.

Table 3: Recommended Treatment Duration - Victrelis® Assessment (HCV-RNA Results) At Treatment At Treatment Recommendation Week 8 Week 24 Previously Undetectable Undetectable Complete triple therapy regimen at week 28 Untreated Detectable Undetectable 1. Continue triple therapy through week 36; then 2. Continue peginterferon/ribavirin through week 48 Previous Partial Undetectable Undetectable Complete triple therapy at week 36 Responders or Detectable Undetectable 1. Continue triple therapy through week 36; then Relapsers 2. Continue peginterferon/ribavirin through week 48 Previous Null Detectable or Undetectable Complete triple therapy at week 48 Responders Undetectable

Note: patients with compensated cirrhosis should receive 4 weeks of peginterferon/ribavirn followed by 44 weeks of Victrelis® in combination with peginterferon/ribavirin

® Table 4: Recommended Treatment Duration – Sovaldi Recommendation Combination with P* and R* Combination with R* Genotype 1, 3, 4 Complete triple therapy through week 12 Complete dual therapy through week 24 Genotype 2 Complete triple therapy through week 12 Complete dual therapy through week 12

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4 of 17 All type, n/a Complete dual therapy through week 48 hepatocellular or until liver transplant, whichever occurs carcinoma awaiting first liver transplantation *: P= peginterferon, R= ribavirin

TM Table 5: Recommended Treatment Duration – Olysio Recommendation Previously 1. Continue triple therapy through week 12; then Untreated 2. Continue peginterferon/ribavirin through week 24 Previous non- 1. Continue triple therapy through week 12; then responders 2. Continue peginterferon/ribavirin through week 48

Due to the side effects and contraindications associated with peginterferon and ribavirin therapy, candidates for therapy must be carefully screened and monitored throughout their course of therapy. Contraindications to therapy include decompensated cirrhosis, pregnancy, uncontrolled depression or severe mental illness, active substance abuse in the absence of concurrent participation in a drug treatment program, advanced cardiac or pulmonary disease, severe cytopenias, poorly controlled diabetes, retinopathy, seizure disorders, immunosuppressive treatment, autoimmune diseases, or other inadequately controlled comorbid conditions. The table below lists common side effects associated with interferon and ribavirin.

Table 6: Common side effects associated with interferon and ribavirin therapy Interferon Ribavirin Flu like symptoms, bone marrow suppression, Hemolytic anemia, chest congestion, dry cough, emotional effects, autoimmune disorders, hair dyspnea, pruritis, sinus disorders, rash, gout, loss, rash, diarrhea, sleep disorders, visual nausea, diarrhea, teratogenicity disorders, weight loss, seizures, hearing loss, pancreatitis, interstitial pneumonitis, injection site reactions

HIV Co-Infection Special consideration does need to be given to those members who are co-infected with HIV, as a number of antitretroviral agents do interact with Sovaldi® and OlysioTM. Please refer to table 6 for allowable antiretroviral therapies for patients with HIV who are being treated with Sovaldi® and/or OlysioTM for hepatitis C.

BMC HealthNet Plan – Hepatitis C

5 of 17 Table 7: Allowed Antiretroviral Therapy in Patients with Hepatitis C Taking Sovaldi® and OlysioTM Hepatitis C Agent Allowable Antiretroviral Therapy in Patients with HIV Sovaldi® All antiretroviral agents can be used EXCEPT • Didanosine • Zidovudine • Tipranavir OlysioTM LIMIT antiretroviral therapy to the following agents: • Raltegravir • Rilpivirine • Maraviroc • Enfuvirtide • Tenofovir • Emtricitabine • Lamiviudine • Abacavir

Acute Hepatitis C

Patients with acute Hepatitis C have a high risk of developing chronic Hepatitis C. For this reason, it is recommended that patients diagnosed with acute Hepatitis C be considered for treatment with interferon based therapy. Response rates are higher in treatment of acute hepatitis C (83% to 100%) than in chronic hepatitis C and the rate of spontaneous viral resolution in these patients is less than 50%. Since some patients will spontaneously clear the virus, treatment may be delayed for 8-12 weeks to allow for spontaneous resolution. Current recommendations for interferon therapy are for at least 12 weeks with consideration of 24 weeks. There are no recommendations at this time for either addition or omission of ribavirin.

Clinical Guideline Statement The Plan may authorize coverage of specific hepatitis C products for members meeting the following criteria: Policy Applicability by Product Medication BMC Health Plan MassHealth CWC COMM QHP ® Incivek X X X X Infergen X X X X TM Olysio X X X X Pegasys X X X X

BMC HealthNet Plan – Hepatitis C

6 of 17 Medication BMC Health Plan MassHealth CWC COMM QHP Peg-Intron X X X X ® Rebetol sol X X X X Brand name* ribavirin convenience pack X X X NF ® Sovaldi X X X X ® Victrelis X X X X NF=non-formulary *= brand name with interchangeable generic available will be reviewed under mandatory generic policy

Prior Authorization- (Duration of approval- see Appendix A)

Chronic Hepatitis C Approval Criteria- Chronic Hep C All requests for chronic hepatitis C regimen require the documentation of all the following:

• Medication is prescribed by or in collaboration with a gastroenterologist, hepatologist, or infectious disease specialist

• A diagnosis of hepatitis C with detectable hepatitis C viral load

• Absence of decompensated liver disease

• Member has not abused illicit substances, narcotics, or alcohol for at least 6 months

• Absence of untreated depression

• Absence of drug-drug interactions with or contraindications to requested hepatitis C regimen

• Presence of cirrhosis or bridging/moderate to severe fibrosis stage >3 defined by histologic scoring system* (e.g. METAVIR), fibrosis markers* (e.g. FibroTest), or radiologic tests*; OR

HIV co-infection with nonsuppressable HIV viral load or with elevated MELD scores;

BMC HealthNet Plan – Hepatitis C

7 of 17 Approval Criteria- Chronic Hep C OR

There is urgency for treatment such as: need for hepatotoxic treatment or immunosuppression**, and extra-hepatic complications associated with HCV**

• An assessment has been conducted demonstrating the member’s readiness and likelihood of success with treatment. At a minimum, the assessment must indicate the following:

o No history of medication and appointment non-adherence; AND

o No history of treatment failure with prior hepatitis C treatment due to nonadherence; AND

o Member has been or will be enrolled in a compliance monitoring program offered by the prescriber or Plan’s preferred specialty pharmacy hepatitis care management program; AND

o Other barriers to treatment completion have been addressed Documentation of the following is also required for continuation after an initial authorization: • Medication adherence, as evidenced by pharmacy claims and/or office notes; AND • Documentation of office visit and lab work adherence

* Copy of scores or images required ** specific treatment and complication description required

In addition to the above, requests for each regimen below may be approvable when the following criteria are met. Limitations apply (see section on Limitations).

Triple Therapy – Sovaldi/pegylated interferon/ribavirin

1. A diagnosis of HCV with genotype 1 or 4; OR

A diagnosis of HCV with genotype 2 or 3; AND

Documented treatment history of null/partial responders; AND

BMC HealthNet Plan – Hepatitis C

8 of 17 Approval Criteria- Chronic Hep C Documentation that the addition of peginterferon outweighs the potential benefit associated with the dual therapy of Sovaldi® in combination with ribavirin; AND

2. If member has HIV: antiretroviral regimen does not include didanosine, zidovudine, or tipranavir

Dual Therapy – Sovaldi/Olysio

1. A diagnosis of HCV with genotype 1; AND

2. No previous exposure to a HCV protease inhibitor (boceprevir, telaprevir, or Olysio); AND 3. Documentation that the member is interferon ineligible (refer to table 1 for definition of “interferon ineligible”); AND 4. The risk of deferring treatment outweighs the benefit; AND 5. If member has HIV: antiretroviral regimen is LIMITED to raltegravir, rilpivirine, maraviroc, enfuvirtide, tenofovir, emtricitabine, lamivudine, and abacavir

Dual Therapy – Sovaldi/ribavirin

1. A diagnosis of HCV with genotype 1; AND

Documentation that the member is interferon ineligible (refer to table 1 for definition of “interferon ineligible”); AND

Documentation of clinical rationale why dual therapy with Sovaldi/ribavirin outweighs the potential benefit of Sovaldi/Olysio combination (e.g., member has drug-drug interactions with Olysio, had a null response to a hepatitis C protease inhibitor); AND

If member has HIV: antiretroviral regimen does not include didanosine, zidovudine, or tipranavir; OR

2. A diagnosis of HCV with genotype 4; AND

Documentation that member is interferon ineligible (refer to table 1 for definition

BMC HealthNet Plan – Hepatitis C

9 of 17 Approval Criteria- Chronic Hep C of “interferon ineligible”); AND

If member has HIV: antiretroviral regimen does not include didanosine, zidovudine, or tipranavir; OR

3. A diagnosis of HCV with genotype 2 or 3; AND

If member has HIV: antiretroviral regimen does not include didanosine, zidovudine, or tipranavir; OR

4. A diagnosis of HCV with any genotype with hepatocellular carcinoma awaiting liver transplantation; AND

If member has HIV: antiretroviral regimen does not include didanosine, zidovudine, or tipranavir

Triple Therapy – Olysio/pegylated interferon/ribavirin

Initial Therapy

1. A diagnosis of HCV with genotype 1 monoinfection; AND

2. Absence of NS3 Q80K polymorphism; AND

3. No previous history of using a regimen inclusive of HCV protease inhibitors (i.e., Incivek®, Olysio™, Victrelis®); AND

4. Documented treatment history of treatment naïve, null/partial responders, or relapsers; AND

5. If member has HIV: antiretroviral regimen is LIMITED to raltegravir, rilpivirine, maraviroc, enfuvirtide, tenofovir, emtricitabine, lamivudine, and abacavir.

Continued Therapy

1. A HCV-RNA level of <25 IU/ML at treatment week 4

BMC HealthNet Plan – Hepatitis C

10 of 17 Approval Criteria- Chronic Hep C

Extended Therapy (for null and partial responder only)

1. A HCV-RNA level of <25 IU/ML at treatment week 12

Additional Therapy (for null and partial responder only)

1. A HCV-RNA level of <25 IU/ML at treatment week 24

Triple Therapy – Incivek/pegylated interferon/ribavirin

Initial Therapy

1. A diagnosis of HCV with genotype 1 monoinfection; AND 2. Documented treatment history of treatment naïve, null/partial responders, or relapsers.

Continued Therapy

1. A HCV-RNA level of ≤ 1000 IU/ML at treatment week 4

Extended Therapy

1. A HCV-RNA level of ≤ 1000 IU/ML at treatment week 4 and/or 12, or is a prior partial or null responder; AND

2. An undetectable HCV-RNA level at treatment week 24

Triple Therapy – Victrelis/pegylated interferon/ribavirin

Initial Therapy

1. A diagnosis of HCV with genotype 1 monoinfection; AND

BMC HealthNet Plan – Hepatitis C

11 of 17 Approval Criteria- Chronic Hep C 2. Documented treatment history of treatment naïve, null/partial responders, or relapsers.

Continued Therapy

1. A HCV-RNA level of <100 IU/ML at treatment week 12

Extended Therapy (for null and partial responder only)

1. A detectable or undetectable HVC-RNA level at treatment week 8, or is a null- responder (< 2 log drop at treatment week 12 from baseline), or a poor responder (< 1 log drop at treatment week 4 from baseline) with previous peginterferon/ribavirin therapy; AND

2. An undetectable HCV-RNA level at treatment week 24

Acute Hepatitis C Approval Criteria- Acute Hep C Pegylated Interferon with or without ribavirin 1. A diagnosis of acute HCV with any genotype

Brand name ribavirin convenience pack Approval Criteria- brand name ribavirin Documentation of the following: 1. The above criteria for dual or triple therapy have been met; AND 2. A failed trial of individually prescribed generic ribavirin due to poor compliance Note: brand name with interchangeable generic available will be reviewed under mandatory generic policy

Rebetol® Solution Approval Criteria- Rebetol® Solution*

BMC HealthNet Plan – Hepatitis C

12 of 17 Approval Criteria- Rebetol® Solution* Documentation of the following: 1. The above criteria for dual or triple therapy have been met; AND 2. Swallowing difficulties due to a clinical condition

Note: Rebetol® Solution does not require PA for members less than or equal to 12 years of age.

Appendix A

Chronic Hepatitis C Approval Duration (Note: total treatment duration in parentheses) tm Sovaldi / Ribavirin Ribavirin Sovaldi® Diagnosis of chronic hepatitis C genotype 1, 3, 4 Initial Therapy up to 8 weeks up to 8 weeks Continuation Therapy up to 16 weeks (24 weeks) up to 16 weeks (24 weeks) Diagnosis of chronic hepatitis C genotype 2 Initial Therapy up to 8 weeks up to 8 weeks Continuation Therapy up to 4 weeks (12 weeks) up to 4 weeks (12 weeks) Continuation Therapy (beyond 12 up to 4 weeks (16 weeks) up to 4 weeks (16 weeks) weeks)—Member is cirrhotic and treatment experienced(Documentation demonstrating cirrhosis and previous treatment is required) All Diagnosis of chronic hepatitis C genotype, hepatocellular carcinoma awaiting liver transplantation Initial Therapy up to 8 weeks up to 8 weeks Continuation Therapy up to 40 weeks or transplant date, up to 40 weeks or transplant date, whichever is shorter; continuation whichever is shorter; continuation therapy will be approved in 8 week therapy will be approved in 8 week increments (up to 48 weeks total) increments (up to 48 weeks total) Sovaldi®/OlysioTM OlysioTM Sovaldi® Diagnosis of chronic hepatitis C genotype 1 Initial Therapy up to 8 weeks up to 8 weeks Continuation Therapy up to 4 weeks (12 weeks) up to 4 weeks (12 weeks) Sovaldi®/Peginterferon/Ribavirin Peginterferon/Ribavirin Sovaldi® Initial Therapy up to 8 weeks up to 8 weeks Continuation Therapy up to 4 weeks (12 weeks) up to 4 weeks (12 weeks) OlysioTM/Peginterferon/Ribavirin Peginterferon/Ribavirin OlysioTM Initial Therapy up to 6 weeks up to 6 weeks Continued Therapy Treatment naïve or relapser up to 18 weeks (24 weeks) up to 6 weeks (12 weeks) Null or partial responders up to 8 weeks (14 weeks) up to 6 weeks (12 weeks)

BMC HealthNet Plan – Hepatitis C

13 of 17 Chronic Hepatitis C Approval Duration (Note: total treatment duration in parentheses) Extended Therapy (null or partial responders only) up to 12 weeks (26 weeks) Not approvable Additional Therapy (null or partial responders only) Up to 22 weeks (48 weeks) Not approvable Incivek®/Peginterferon/Ribavirin Peginterferon/Ribavirin Incivek® Initial Therapy up to 8 weeks up to 8 weeks Continued Therapy up to 16 weeks (24 weeks) up to 4 weeks (12 weeks) Extended Therapy up to 24 weeks (48 weeks) Not approvable Victrelis®/Peginterferon/Ribavirin Peginterferon/Ribavirin Victrelis® Initial Therapy up to 14 weeks up to 14 weeks Continued Therapy up to 12 weeks (26 weeks) up to 12 weeks (26 weeks) Extended Therapy Treatment Naïve Undetectable at TW 8 up to 2 weeks (28 weeks) up to 2 weeks (28 weeks) Detectable at TW 8 up to 22 weeks (48 weeks) up to 10 weeks (36 weeks) Extended Therapy Partial/Relapsers Undetectable at TW 8 up to 10 weeks (36 weeks) up to 10 weeks (36 weeks) Detectable at TW 8 up to 22 weeks (48 weeks) up to 10 weeks (36 weeks) Extended Therapy Null Responder/Poor Responder up to 22 weeks (48 weeks) up to 22 weeks (48 weeks)

Acute Hepatitis C Approval Duration Peginterferon w/ or w/o Ribavirin Diagnosis of chronic hepatitis C genotype 1 Initial Therapy up to 24 Weeks Diagnosis of chronic hepatitis C genotype 2, 3, 4 Initial Therapy Up to 12 weeks

Appendix B

Fibroscan 2.5-7 kPa Mild or absence of fibrosis 7-12 kPa F2 >12.5 kPa F3-F4

METAVIR F0 No fibrosis F1 Portal fibrosis without septa F2 Portal fibrosis with few septa

BMC HealthNet Plan – Hepatitis C

14 of 17 F3 numerous septa w/o cirrhosis F4 Cirrhosis

Fibrotest METAVIR proposed conversion Fibrotest METAVIR 0.00-0.21 F0 0.22-0.27 F0-F1 0.28-0.31 F1 0.32-0.48 F1-F2 0.49-0.58 F2 0.59-0.72 F3 0.73-0.74 F3-F4 0.75-1 F4

Limitations The Plan will not approve coverage of the above treatment of Hepatitis C in the following instances:

• Diagnoses not listed in the policy • When the above criteria have not been met. • Members < 3 years of age for peginterferon ® ® ® TM • Members < 18 years of age for Victrelis , Incivek , Sovaldi and Olysio • Infergen® or any regimen combination (or monotherapy) not addressed with specific approval criteria in the policy • Member is pregnant • Request for the same regimen that has been failed previously

Clinical Background Information and References 1. Chopra S. Overview of the management of chronic hepatitis C virus. Up to Date®. Last updated Dec 3, 2013, accessed Feb 09, 2014. Available from: http://www.uptodate.com. 2. Chopra S. Treatment regimens for chronic hepatitis C virus Diagnosis of chronic hepatitis C genotype 1. Up to Date®. Last updated Dec 19, 2013, accessed Feb 09, 2014. Available from: http://www.uptodate.com.

BMC HealthNet Plan – Hepatitis C

15 of 17 3. Chopra S. Treatment regimens for chronic hepatitis C virus Diagnosis of chronic hepatitis C genotypes 2, 3, and 4. Up to Date®. Last updated Feb 12, 2014, accessed Feb 26, 2014. Available from: http://www.uptodate.com. 4. American gastroenterological association medical position statement on the management of hepatitis C. Gastroenterology 2006;130:225-230. 5. Incivek® [package insert]. Cambridge (MA): Vertex Pharmaceuticals Incorporated; Apr 2013. 6. Victrelis® [package insert]. Whitehouse Station (NJ): Schering Corporation, a subsidiary of Merck & Co. Inc.; Feb 2013. 7. Sovaldi® [package insert]. Foster City (CA): Gilead Science, Inc.; Dec 2013. 8. OlysioTM [package insert]. Titusville (NJ): Janssen Therapeutics, LP; Nov 2013. 9. Recommendations for Testing, Managing, and Treating Hepatitis C. American Association for the Study of liver Disease (AASLD) practice guidelines. Accessed June 10, 2014. Available from http://www.aasld.org 10. Doris N., Jayant T. noninvasive assessment of Liver Fibrosis. Diagnostic and Therapeutic Advances in Hepatology. Accessed Mar 13, 2014. Available from http://www.aasld.org 11. Xin Sun, PhD, Carrie D Patnode, PhD, MPH, et al. Interventions to Improve Patient Adherence to Hepatitis C Treatment Comparative Effectiveness. Comparative Effectiveness Reviews, No 91. Agency for Healthcare Research and Quality(US); Dec 2012. Accessed Mar 10, 2014. Available from: http://www.ncbi.nlm.nih.gov. 12. Michael P C., MD et al. Tests used for the noninvasive assessment of hepatic fibrosis. Up to Date®. Last updated Dec 3, 2013, accessed Mar 11, 2014. Available from: http://www.uptodate.com

Policy History

Effective Date: 09/08/2003

Review Dates Dates of Review/Revision: 7/14/2005 - Added additional criteria to the “Clinical Coverage Criteria”, and approvable Hepatitis B criteria for treatment. 9/12/2005 - Added approvable criteria for non-Hepatitis indications. 9/27/2007 - P&T Annual review, -Specialty requirements for prescribers removed, -Lower age limit added for interferon/ribavirin therapy, -Title changed from, “Hepatitis” to Hepatitis C”, -Criteria for non-Hepatitis C indications removed, 07/10/2008 - P&T Annual Review, no changes required. 07/09/2009 - P&T Annual Review, criteria added for extended therapy for “slow responders”, criteria added for acute hepatitis C 07/08/2010 - P&T Annual Review, no changes required 07/14/2011 - P&T Annual Review, criteria added for Victrelis®, Incivek®, Ribapak® Pak, and Rebetol®, policy applied to Commercial 07/12/2012 - P&T Annual Review, modified criteria language for Ribapak® Pak, and Rebetol®

BMC HealthNet Plan – Hepatitis C

16 of 17 7/11/2013 – P&T Annual Review, increased initial treatment duration for all components of Incivek® triple therapy to 8 weeks, included black box warning for Incivek® into background information, modified criteria and treatment duration for Victrelis® triple therapy for patients with compensated cirrhosis, minor formatting changes throughout. 12/13/2013 – Policy applied to ConnectorCare/Qualified Health Plan (QHP) 03/13/2014- P&T Annual Review, added criteria for Sovaldi and Olysio, removed section for dual therapy of peginterferon in combination with ribavirin, and section for monotherapy of interferon alfacon (case by case review since these are no longer recommended by AASLD; added general coverage requirements and limitations applicable to all hepatitis C regimen request

Last Review/Revision Date: 07/10/2014 – P&T Annual Review. Defined interferon ineligibility, added criteria for Sovaldi and Olysio combination, added continuation criteria and adjusted approval durations for initial and continuation criteria, added criteria regarding antiretroviral drug-drug interactions for Sovaldi and Olysio, added extended approval criteria for Sovaldi and ribavirin in genotype 2 with cirrhotic treatment experienced patients, added a time frame of 6 months for absence of substance/alcohol abuse, added requirement of no history of medication and appointment nonadherence for initial approval criteria, added pregnancy as a limitation

Next Review Date: 07/09/2015

Approval Dates Regulatory Approval: N/A Internal Approval: Initial approval by Pharmacy & Therapeutics Committee – September 08, 2003 Authorizing Entity: P&T Committee

Important Notes:

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Clinical Coverage Guidelines Growth Hormones and IGF-1

BMC HealthNet Plan Well Sense Health Plan

Policy Applicability MassHealth New Hampshire Medicaid Commonwealth Care Commercial ConnectorCare/Qualified Health Plan (QHP)

Effective Date: 11/12/2014 Policy Number: 9.125 Policy Effective Date: 09/11/2003 Last Review Date: 07/10/2014 Approved by: Pharmacy and Therapeutics Committee Policy Owner/Title: Pharmacy Services

Summary BMC HealthNet Plan will authorize coverage of growth hormones and insulin-like growth factors for the treatment of approved indications when appropriate criteria are met.

Description of Item or Service Growth hormone (GH) therapy is indicated to treat growth hormone deficiency in both adults and children. It is also indicated for treatment of certain conditions where GH administration has been shown to be effective, although the condition is not associated with GH insufficiency (e.g. Turners syndrome, AIDS wasting). FDA

BMC HealthNet Plan – Growth Hormones and IGF-1

1 of 6 indications for use of GH in adults include pituitary disease from known causes, including pituitary tumor, pituitary surgical damage, hypothalamic disease, irradiation, trauma, reconfirmed childhood GH deficiency, and cachexia associated with AIDS. Pediatric indications are listed below:

• GH deficiency • Turner syndrome • Chronic renal insufficiency • Small for gestational age or intrauterine growth retardation • Prader-Willi syndrome • Continued height deficit at puberty • Cachexia associated with AIDS

Although the available GH products are not chemically identical to each other and may have different labeled indications, they are considered to be similar in their clinical effect for treating growth hormone deficiency. IGF-1 is indicated in pediatric patients with severe primary IGF-1 deficiency. Increlex® is the only IGF-1 product currently available on the market with primary IGF-1 deficiency and other short stature indications.

Clinical Guideline Statement BMC HealthNet Plan may authorize coverage of prescriptions for growth hormone products for members meeting the following criteria:

Prior Authorization - Growth Hormones

A prior authorization request will be required for all prescriptions for growth hormone products. These requests will be approved when the following criteria are met:

Condition Clinical Criteria Tev-Tropin® and Norditropin® are the preferred growth Hormone products for BMCHP. Pediatric Growth Documentation of the following: Hormone Deficiency 1. A diagnosis of Pediatric growth hormone deficiency; AND (approval for up to 12 2. A subnormal growth velocity (age or pubertal status specific growth months) rate at less than the 10th percentile) or 2 SD below mean; AND 3. A subnormal GH response to a provocative stimulation test (2 tests) [a maximum GH level of < 10ng/ml] Panhypopituitarism Documentation of the following: (life time approval) 1. A diagnosis of panhypopituitarism; AND 2. There are deficiencies in growth hormone and at least one other pituitary hormone. Chronic Renal Documentation of the following:

BMC HealthNet Plan – Growth Hormones and IGF-1

2 of 6 Condition Clinical Criteria Insufficiency 1. A diagnosis of Chronic Renal Insufficiency in a child; AND (Approval for up to 12 2. Conditions such as anemia, active malignancies, renal osteodystrophy, months) metabolic acidosis, malnutrition or fluid and electrolyte imbalance have been ruled out; AND 3. Evidence of growth impairment (the mean Z-score for growth velocity <-2 or mean Z-score for height based on age and gender <-1.88). Turners Syndrome Documentation of the following: and Noonan’s 1. A diagnosis of Turners Syndrome or Noonan’s Syndrome; AND Syndrome (approval 2. A height below 5th percentile for age. for up to 12 months) Prader – Willi Documentation of the following: Syndrome (lifetime 1. A diagnosis of Prader-Willi Syndrome and growth hormone deficiency approval) Small for Gestational Documentation of the following: Age Children 1. Member is a child born small for gestational age; AND (Approval for up to 12 2. Height remains below 2 Standard deviation scores below the mean at months) 2 years of age. Cachexia associated Documentation of the following: with AIDS (Approval for up to 12 months) 1. A diagnosis of cachexia associated with AIDS; AND 2. A failure of at least one other intervention addressing malnutrition.

Adult growth Documentation of the following: Hormone Deficiency 1. Severe GH deficiency confirmed by a peak GH response of < 5 ng/mL (lifetime approval for during insulin tolerance tests (ITTs) or confirmed via alternative tests panhypopituitarism; when ITTs are contraindicated: growth-hormone releasing hormone- approval for up to 12 arginine or glucagon stimulation (2 tests required); OR months for all other 2. GHD in childhood due to structural lesions with multiple hormone criteria) deficiencies or those with proven genetic causes AND low IGF-1 levels after at least 1 month off of GH therapy; OR 3. History of idiopathic childhood GHD with documentation of at least 1 subnormal provocative stimulation test after age 18; OR 4. A diagnosis of panhypopituitarism AND low serum IGF-I level All other growth Documentation of the following: hormone (somatropin) products 1. One of the conditions listed above and all applicable clinical criteria; AND 2. An inadequate response after at least two consecutive 6-month periods of Tev-Tropin® and Norditropin® therapy. Continuation of therapy – BMC HealthNet Plan may authorize continuation of coverage for growth hormone products when the following criteria are met:

BMC HealthNet Plan – Growth Hormones and IGF-1

3 of 6 Condition Clinical Criteria Children (Approval Documentation of the following: for additional 12- 1. A growth rate > 2.5cm/yr (post-pubertal growth) or > 4.5cm/yr (pre- months) pubertal growth). Adults (Approval for 1. Documentation of clinical benefit (increase in lean body additional 12-months) mass/decreased fat mass, increase in IGF-1, or IGFBP-3, or an increase in exercise capacity). Increlex® - Increlex® is approvable for pediatric use age 2 or older, when the criteria below are met. Insulin-like growth factor should not be used for treatment of growth failures in adults. Growth Failure Due to Documentation of the following: Severe Primary IGF-1 1. A diagnosis of growth failure due to severe primary IGF-1 deficiency Deficiency (initial including: approval for up to 12 • Height standard deviation score < -3.0 months) • Basal IGF-1 standard deviation score < -3.0 • Normal or elevated growth hormone (GH); OR

A diagnosis of growth failure due to GH gene deletion with neutralizing antibodies to GH; AND

2. The treating physician is an endocrinologist or has consulted with an endocrinologist; AND 3. Absence of the following contraindications to IGF-1 therapy • GH deficiency malnutrition • Hypothyroidism • Chronic treatment with pharmacologic doses of anti-inflammatory steroids Continuation of IGF-1 Documentation of the following: Therapy (Approval for 1. Tolerable or no side effects and compliance with therapy; AND additional 12 months) 2. Demonstrated the expected increase in height velocity.

Limitations 1. BMC HealthNet Plan will not approve coverage of growth hormones or IGF-1 products if the above criteria are not met. 2. BMC HealthNet Plan will not approve coverage of non-preferred growth hormones if the above criteria related to these products are not met.

Clinical Background Information and References 1. Evaluation and treatment of adult growth hormone deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jun;96(6):1587-609.

BMC HealthNet Plan – Growth Hormones and IGF-1

4 of 6 2. American association of clinical endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children – 2003 update. Endocrine practice; Vol 9 (1), Jan/Feb 2003. 3. Somatropin. In DrugDex® System (internet database). Version 5.1, Greenwood Village, Colo. Thomson Micromedex. Accessed June 2007. 4. Mecasermin. In DrugDex® System (internet database). Version 5.1, Greenwood Village, Colo. Thomson Micromedex. Accessed June 2007. 5. Waknine, Yael. FDA safety changes: Duetact®, Norditropin®, Nutropin®, Nutropin AQ®, Tev-Tropin®. Medscape Medical News. May 2007. Available from: http://www.medscape.com/viewarticle/555924. 6. Tonshoff, B. Growth hormone treatment in children with chronic kidney disease and post renal transplantation. UptoDate® Accessed June 2014. 7. Tev-Tropin® (package insert). Horsham (PA): Teva; Nov 2013. 8. Lee PA, Chernausek SD, Hokken-Koelega ACS, Czernichow P. International small for gestation age advisory board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001. Pediatrics. 2003;111:1253-1261.

Policy History

Effective Date: 10/01/2013

Review Dates Dates of Review/Revision: 7/14/2005 - Contraindications of Nutropin®. 9/12/2005 - Added additional criteria for Serostim®. 5/11/2006 - Added criteria for insulin-like growth factors. 9/25/2006 - Added criteria for Iplex®. 07/12/2007 - Added Tev-Tropin® as preferred product, added criteria for Omnitrope®, removed requirement for X-ray documentation of non-fused epiphysis for renewal of therapy in children. 07/10/2008 – P&T Annual Review, indication for Noonan’s Sydrome added, diagnostic requirements for Adult GH deficiency changed. 07/09/2009 – P&T Annual Review, no changes required 07/08/2010 – P&T Annual Review, HIV cachexia indication no longer exempt from preferred product requirement, approval durations updated for Prader-Willi Syndrome (lifetime approval), SGA (12 months), and HIV cachexia (12 months). 07/14/2011 – P&T Annual Review, criteria for adult growth hormone deficiency updated, policy applied to Commercial 07/12/2012 – P&T Annual Review, no changes required 07/11/2013 – P&T Annual Review, criteria for children with chronic renal insufficiency modified to allow GH use in post renal transplantation, criteria for small for gestational age children revised, minor formatting throughout 12/13/2013 – Policy applied to ConnectorCare/Qualified Health Plan (QHP) Last Review/Revision Date: 07/10/2014 – P&T Annual Review, added Norditropin® as a preferred agent

BMC HealthNet Plan – Growth Hormones and IGF-1

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Next Review Date: 07/09/2015

Approval Dates Regulatory Approval: N/A Internal Approval: Initial approval by Pharmacy & Therapeutics Committee – September 11, 2003 Authorizing Entity: P&T Committee

Important Notes:

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bmchp.org | 888-566-0008 wellsense.org | 877-957-1300

Clinical Coverage Guidelines Botulinum Toxins - Botox®, Dysport®, Myobloc®, Xeomin®

BMC HealthNet Plan Well Sense Health Plan

Policy Applicability MassHealth New Hampshire Medicaid Commonwealth Care Commercial ConnectorCare/Qualified Health Plan (QHP)

Effective Date: 11/12/2014 Policy Number: 9.106 Policy Effective Date: 07/10/2013 Last Review Date: 07/10/2014 Approved by: Pharmacy and Therapeutics Committee Policy Owner/Title: Pharmacy Services

Summary BMC HealthNet Plan may authorize coverage of Botox®, Dysport®, Myobloc®, and Xeomin® when appropriate criteria are met.

BMC HealthNet Plan – Botulinum Toxin

Non-FDA Approved Indications for onabotulinumtoxinA

• Achalasia

BMC HealthNet Plan – Botulinum Toxin

Clinical Guideline Statement Policy Applicability by Product BMC HealthNet Plan Medication MassHealth CWC COMM QHP Botox X X X X Dysport X X X X Myobloc X X X X Xeomin X X X X

BMC HealthNet Plan may approve coverage of Botox®, Dysport®, Myobloc®, and Xeomin® for members meeting the following criteria:

Prior Authorization – (Duration of Approval – Maximum of 6 month for the indication of chronic migraine prophylaxis (Botox only®)*; Maximum of 1 year for all other indications)

A prior authorization request will be required for all prescriptions for Botox®, Dysport®, Myobloc®, and Xeomin®. These requests will be approved when the following criteria are met:

Initial therapy

Botox®

1. Documentation of one of the following diagnoses: • Cervical dystonia or Spasmodic torticollis and age is 16 years or older • Blepharospasm and age is 12 years or older

BMC HealthNet Plan – Botulinum Toxin

Diagnosis has been confirmed by a neurologist consult; and

*Recommended dose= 155U/12 weeks

BMC HealthNet Plan – Botulinum Toxin

Dysport®

1. Documentation of a diagnosis of cervical dystonia and age is 18 years or older.

Myobloc®

Xeomin®

1. Documentation of a diagnosis of blepharospasm or cervical dystonia and age is 18 years or older; and An inadequate response, intolerance, or contraindication to a trial of Botox®

Continuation of Therapy

Prior Authorization is required for all prescriptions for continued treatment beyond the initial approval duration. These requests will be approved when the following criteria are met:

1. Documentation of clinically significant reduction in symptom severity/ frequency, or improvement of functional ability.

BMC HealthNet Plan – Botulinum Toxin

5 of 8 Applicable HCPCs codes

Drug Name HCPCs code

Botox® (onabotulinumtoxin A) J0585

Dyport® (abotulinumtoxin A) J0586

Myobloc® (rimabotulinumtoxin B) J0587

Xeomin® (incobotulinumtoxin A) J0588

Limitations BMC HealthNet Plan will not approve coverage of Botox®, Dysport®, Xeomin®, or Myobloc® in the following instances:

1. When the criteria above has not been met. 2. When used for treatment of cosmetic indications (i.e. wrinkles).

BMC HealthNet Plan – Botulinum Toxin

Policy History

Effective Date: 07/10/2003

Next Review Date: 07/09/2015

Approval Dates Regulatory Approval: N/A Internal Approval: Initial approval by Pharmacy & Therapeutics Committee – July 10, 2003

BMC HealthNet Plan – Botulinum Toxin

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Important Notes:

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