Formulary decision highlights march 2016

Formulary Decision Highlights: March 9, 2016

Documented below are the decisions from the March 9, 2016 Pharmacy and Therapeutics Committee Meeting.
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KEY
n/a: non-applicable PA: Prior authorization NF: non-formulary ST: Step Therapy MB: Medical benefit
Pharmacy Benefit Decisions
Medications filled at outpatient pharmacies are considered part of the pharmacy benefit.
Drug Name: Naloxone nasal spray (Narcan)
Dosage, Route: Spray, intranasal
Indication: Emergency treatment of known or suspected opioid
Reason for Review: Recent FDA approval
overdose, as manifested by respiratory and/or central nervous system depression. Naloxone nasal spray is not a substitute for emergency medical care. Decision for naloxone nasal spray (Narcan): Add to formulary, no criteria
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status Formulary
Tier 3 (preferred brand) Decision for naloxone auto-injector (Evzio): Remove from formulary
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF
Tier 3 (preferred brand) Coverage Criteria: None
Rationale:
 Naloxone nasal spray is the first FDA-approved nasal spray version of naloxone known to be effective in the
reversal of opioid overdose. FDA approval was based on a bioequivalence study demonstrating comparable pharmacokinetics between naloxone nasal spray and intramuscular injection of naloxone.  Common adverse reactions observed in the pharmacokinetic study are increased blood pressure, musculoskeletal pain, headache, nasal dryness, nasal edema, nasal congestion, and nasal inflammation.  The cost of naloxone nasal spray is lower than the cost of the naloxone auto-injector device.  The nasal spray formulation of naloxone offers easier and more convenient delivery of medication than injectable formulation and eliminates the risk of a contaminated needle stick. Treatment Alternatives: Naloxone auto-injector (NF)
Drug Name: Osimertinib (Tagrisso)
Dosage, Route: Tablet, oral
Indication: Treatment of patients with metastatic EGFR T790M
Reason for Review: Recent FDA accelerated
mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy. Decision: Do not add to formulary, add coverage criteria, add QL
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF with exception
Tier 5 (specialty) Quantity Limit
30 tablets per 30 days Coverage Criteria: Treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer
(NSCLC), as detected by an FDA-approved test, who have progressed on EGFR tyrosine kinase inhibitor (TKI)
therapy.
Rationale:
 Osimertinib was approved by the FDA under the accelerated approval process based on favorable response rate
data because there is no other therapy that specifically targets the EGFR T790M mutation.  The FDA approval of osimertinib for metastatic EGFR T790M mutation-positive NSCLC with progression after EGFR TKI was based on preliminary data from two single-arm Phase 2 studies (AURA extension and AURA2) reporting about 60% overall response rate and results from a Phase 1 study (AURA) demonstrating durable response.  In clinical trials, osimertinib was associated with limited GI and skin side effects and rare QTc prolongation. Other EGFR TKIs have been associated with GI and skin side effects, but not QTc prolongation.  Osimertinib has a higher cost compared to the first line formulary alternative erlotinib. However, osimertinib is the first EGFR TKI FDA approved to specifically target the EGFR T790M mutation.  Results from continued follow-up of the AURA extension and AURA2 trials, as well as data from the AURA3 trial, are needed to fully understand the clinical benefit in terms of progression free survival and effectiveness compared to other second line therapies. Treatment Alternatives: Cisplatin (MB), carboplatin (MB), paclitaxel (MB), docetaxel (MB), gemcitabine (MB),
pemetrexed (MB), vinorelbine (MB), etoposide (MB), erlotinib (F-PA), afatinib (F-PA), gefitinib (F-PA)
Drug Name: Afatinib (Gilotrif), Erlotinib (Tarceva), Gefitinib (Iressa)
Dosage, Route: Tablet, oral
Indication: First-line treatment of patients with metastatic non-small cell
Reason for Review: Recent FDA approval
lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Decision for afatinib (Gilotrif): Add to formulary, update PA, maintain QL, declare therapeutically interchangeable
with erlotinib and gefitinib
Decision for erlotinib (Tarceva): Remain formulary, update PA, maintain QL, declare therapeutically interchangeable
with afatinib and gefitinib
Decision for gefitinib (Iressa): Add to formulary, add PA, add QL, declare therapeutically interchangeable with afatinib
and erlotinib
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status Formulary with PA
Tier 5 (specialty) Quantity Limit
30 day supply per fill Coverage Criteria:
For treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients who belong to one of
the following groups.
1. For patients who are chemotherapy naïve and whose epidermal growth factor receptor (EGFR) expression status is positive for mutation. 2. For patients who have failed at least 1 prior chemotherapy regimen and whose epidermal growth factor receptor (EGFR) expression status is either is positive for mutation or unknown due to inability to collect sufficient tissue sample for testing (i.e. do not cover if the test for EGFR mutation is negative). Not covered if patient experiences progression on another EGFR tyrosine kinase inhibitor. Note: For patients with unknown EGFR mutation status, medication will initially be authorized for 6 weeks. Continuous coverage will be contingent on attestation from the provider that there has been a clinical benefit. Rationale:
 Gefitinib was the first approved EGFR tyrosine kinase inhibitor. It voluntarily was removed from the market when it
could not demonstrate overall survival in an unselected patient population. Since then, EGFR testing allows for targeted treatment, and gefitinib has been re-introduced to the market.  Several meta-analyses demonstrate superiority of EGFR TKIs when compared to chemotherapy in the first-line treatment of EGFR positive NSCLC. Additionally, indirect comparisons between EGFR TKIs demonstrate comparable safety and efficacy.  Gefitinib, afatinib, and erlotinib were declared therapeutically interchangeable due to evidence of comparable efficacy, safety, and cost. Current costs of gefitinib, erlotinib, and afatinib are comparable. Treatment Alternatives: Cisplatin (MB), carboplatin (MB), paclitaxel (MB), docetaxel (MB), gemcitabine (MB),
pemetrexed (MB), vinorelbine (MB), etoposide (MB)
Drug Name: Insulin glargine (Toujeo)
Dosage, Route: Pre-filled syringe,
subcutaneous
Indication: Long-acting human insulin analog indicated to improve
Reason for Review: Recent FDA approval
glycemic control in adults with diabetes mellitus. Decision: Do not add to formulary, add criteria
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF exception criteria
Tier 4 (non-preferred brand)  Specialty Tier  Specialty Tier Coverage Criteria: Type 1 diabetes treatment for patients 18 years of age and older who experience symptomatic
nocturnal hypoglycemia on insulin glargine 100 U/mL.

Rationale:
 The FDA approval of insulin glargine 300 U/mL (Gla-300) was based on the results of Phase 3a EDITION clinical
trials consisting of three randomized, open-label trials in patients with type 2 diabetes mellitus (T2DM) and one trial in those with type 1 diabetes mellitus (T1DM). Gla-300 was shown to be non-inferior to insulin glargine100 U/mL (Gla-100) in the primary endpoint of HbA1c reduction in all four trials.  There were no significant differences in adverse events between Gla-300 and Gla-100, though there was a tendency towards less hypoglycemia with Gla-300 based on mixed results of hypoglycemia in open label trials. Administration related variables lead to day-to-day dose differences. Patients with type 1 diabetes tend to be more sensitive to these variations than patients with type 2 diabetes. The concentrated Gla-300 dosage form provides a consistent basal insulin dose that could benefit patients with type 1 diabetes who experience nocturnal hypoglycemia on insulin Gla-100.  Formulary alternatives include insulin glargine 100 U/mL and neutral protamine Hagedorn insulin (NPH), which are available at a lower cost than Gla-300.
Because Gla-300 showed no clinical benefit in non-inferiority trials and is higher cost, Gla-300 can be considered
in patients with type 1 diabetes with persistent hypoglycemia after trial of formulary alternatives.
Treatment Alternatives: Insulin NPH (F), insulin glargine 100 U/mL (F-PA), insulin detemir (F-PA)
Drug Name: Insulin degludec (Tresiba)
Dosage, Route: Pen, subcutaneous
Indication: Improvement of glycemic control in adults with diabetes
Reason for Review: Formulary status and
Decision: Do not add to formulary, add coverage restriction
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF, not medically
Tier 3, not medically Tier 4 (non-preferred brand)
Coverage Restriction: Not covered, not medically necessary
Rationale:
 The FDA approval of insulin degludec was based on Phase 3 BEGIN clinical trials consisting of nine pivotal Phase
3 trials in patients with type 1 and type 2 diabetes mellitus. Overall, insulin degludec has shown to be non-inferior to insulin glargine and insulin determir in the primary endpoint of HbA1c reduction.  In clinical trials, insulin degludec was associated with lower rates of nocturnal hypoglycemia compared to other long-acting insulin analogs, but results were mixed.  Cardiovascular risk was identified as a concern during the first FDA review of insulin degludec. In the first review, an increased rate of cardiovascular risk of 39 – 67% compared to insulin glargine was observed in many of the clinical trials. There is an ongoing study and additional cardiovascular data will be available. Other adverse events in clinical trials are in line with other insulins.  Insulin degludec is more costly compared to formulary alternatives that include insulin glargine 100 U/mL, NPH, and insulin detemir.  Due to concerns of cardiovascular safety, lack of glucose control benefits, and higher cost, treatment with insulin degludec is not medically necessary. Treatment Alternatives: Insulin NPH (F), insulin glargine (Lantus) (F-PA), insulin detemir (F-PA)
Drug Name: Sacubitril/valsartan (Entresto)
Dosage, Route: Tablet, oral
Indication: To reduce the risk of cardiovascular death and
Reason for Review: Recent FDA approval
hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. Decision: Add to formulary, add criteria
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status Formulary with PA
Tier 3 (preferred brand) Coverage Criteria:
Covered for patients who meet ALL of the following:
 Diagnosis of NYHA class II, III or IV heart failure
 Left ventricular ejection fraction ≤35%
 Currently stable on maximally tolerated dose of a beta-blocker or have intolerance or contraindication  Currently stable on maximally tolerated dose of ACE-inhibitor, or if intolerant to ACE-inhibitor, currently stable on maximally tolerated dose of ARB  Prescribed by or in consultation with a cardiologist Not covered for patients who meet one or more of the following:  History of angioedema  Concomitant use of ACE-inhibitor or ARB  Concomitant use of aliskiren in patients with diabetes  Intolerance to ARB  SBP <95 mmHg or symptomatic hypotension  eGFR <30 ml/min/1.73 m2 Rationale:
 The FDA approval of sacubitril/valsartan was based on the results of one pivotal Phase 3 randomized, double-blind,
active-controlled, multicenter study (PARADIGM-HF), which reported that patients with NYHA Class II-IV heart failure and reduced ejection fraction treated with sacubitril/valsartan had a significant reduction in the primary endpoint of cardiovascular death or hospitalizations compared to enalapril (21.8% vs. 26.5%, respectively. HR 0.80, 95%CI 0.73 to 0.87).  More patients on sacubitril/valsartan experienced symptomatic hypotension and angioedema in sacubitril/valsartan patients compared to enalapril. FDA approval came with two post-marketing safety requirements to evaluate the incidence of angioedema in African American patients and the effects on cognitive function.  Sacubitril/valsartan may be an add-on therapy option for patients with heart failure with reduced ejection fraction (HFrEF) EF ≤ 35%, NYHA Class II-IV who are currently receiving both ACE-inhibitor/ARB and beta-blocker. Treatment Alternatives: Enalapril (F), lisinopril (F), losartan (F), valsartan (F)
Drug Name: Ivabradine (Corlanor)
Dosage, Route: Tablet, oral
Indication: Indicated to reduce the risk of hospitalization for worsening
Reason for Review: Recent FDA approval
heart failure (HF) in patients with stable, symptomatic chronic HF with left ventricular ejection fraction (LVEF) ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute (bpm) and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. Decision: Do not add to formulary, add coverage criteria
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF with exception
Tier 4 (non-preferred brand) Coverage Criteria:
Patients with stable, symptomatic chronic heart failure who meet the following criteria:
 Left ventricular ejection fraction ≤ 35% AND
 In sinus rhythm with resting heart rate ≥ 70 beats per minute AND  Not pacemaker dependent AND  Either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use AND  Failure, intolerance, or contraindication to ACE-I (or ARB) AND  Prescribed by or in consultation with a cardiologist Not covered for patients who meet one or more of the following:  Acute decompensated heart failure  Blood pressure <90/50 mm Hg  Severe hepatic impairment (e.g., ALT/AST ≥3X ULN, total bilirubin >1.5X ULN, etc.)  Acute coronary syndrome (e.g., MI, UA, revascularization) within the past 2 months Rationale:
 FDA approval of ivabradine was based on the double-blind, multi-center, placebo-controlled, randomized SHIFT
trial comparing ivabradine and placebo in patients with stable NYHA class II to IV heart failure (HF), left ventricular ejection fraction ≤ 35%, and resting heart rate ≥ 70 beats per minute. Ivabradine reduced composite endpoint of cardiovascular death or hospital admission due to HF exacerbation (HR 0.82, 95%CI 0.75-0.90). This positive result was primarily driven by a reduction in hospitalization for worsening HF (HR 0.74, 95% CI 0.66-0.83). Cardiovascular death was not significantly reduced with ivabradine (HR 0.91, 95% CI 0.80-1.03).  Safety concerns exist for development of atrial fibrillation or bradycardia with ivabradine use. In the SHIFT trial, atrial fibrillation occurred at a rate of 5.0% vs. 3.9% per patient-year for ivabradine compared to placebo, respectively.  Ivabradine may be considered as add-on to optimized standard therapy in selected patients with stable and symptomatic chronic HF at a higher cost than other alternatives. Treatment Alternatives: Enalapril (F), lisinopril (F), captopril (F), ramipril (F), losartan (F), valsartan (F), metoprolol (F),
carvedilol (F), bisoprolol (F), spironolactone (F), eplerenone (F), hydralazine (F), isosorbide dinitrate (F)
Drug Name: Albuterol (ProAir HFA and RespiClick, Proventil HFA,
Dosage, Route: Aerosol, inhalation
Ventolin HFA)
Indication: Treatment or prevention of bronchospasm in patients with
Reason for Review: QL update
reversible obstructive airway disease; prevention of exercise-induced bronchospasm. Decision for albuterol (ProAir HFA, Ventolin HFA): Remain formulary, update QL
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status Formulary
Tier 3 (preferred brand) Quantity Limit
1 canister per 30 days for patients >18 years of age 2 canisters per 30 days Decision for albuterol (ProAir RespiClick, Proventil HFA): Remain non-formulary, update QL
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF
Tier 4 (non-preferred brand) Quantity Limit
1 canister per 30 days for patients >18 years of age 2 canisters per 30 days for Proventil HFA Coverage Criteria: None
Rationale:
 Asthma Medication Ratio (AMR) is the ratio of controller medications to total asthma medications. Evidence
suggests that AMRs ≥0.4 in patients meeting the HEDIS criteria of persistent asthma are associated with decreased emergency hospital care.  Quantity limits (200 puffs per 30 days) will alert clinicians and the care team to review excessive use of albuterol inhalers. This strategy promotes the use of controller medications, the standard of care for persistent asthma treatment.  The committee balanced the need to review appropriate albuterol use while also making the medication accessible to patients for certain clinically appropriate situations. Treatment Alternative: Beclomethasone (F), mometasone (F-ST), mometasone/formoterol (F-ST)
Drug Name: Econazole (Spectazole)
Dosage, Route: Cream, topical
Indication: Topical application in the treatment of tinea pedis, tinea
Reason for Review: Cost savings strategy
cruris, tinea corporis, cutaneous candidiasis, and tinea versicolor. Decision: Remove from formulary
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF
Tier 1 (preferred generic) Coverage Criteria: None
Rationale:
 Econazole has increased dramatically in price over the past year.
 There is no data to support econazole as being either safer or more efficacious than other less expensive topical  A 2014 Cochrane analysis found no evidence of a difference in mycological or clinical cure rates with either azoles (i.e. miconazole, clotrimazole, econazole) or allylamines (i.e. terbinafine) for the treatment of tinea cruris or tinea corporis. The overall quality of evidence for all of the outcomes studied was low to very low.  A 2009 Cochrane meta-analysis found that, while a number of topical antifungals, such as azoles, were effective in the treatment of tinea pedis, the allylamine class (i.e. terbinafine) was the most effective. Treatment Alternatives: Clotrimazole (OTC), terbinafine (OTC), miconazole (OTC)
Drug Name: Erythromycin (Ery-Tab)
Dosage, Route: Tablet, oral
Indication: Oral administration for treatment of susceptible bacterial
Reason for Review: Cost savings strategy
Decision: Remove from formulary
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF
Tier 1 (preferred generic) Coverage Criteria: None
Rationale:
 Brand and generic erythromycin products have dramatically increased in cost over the past two years.
 Newer macrolide antibiotics (azithromycin and clarithromycin) as well as other antibiotic classes, such as tetracyclines, and cephalosporins, have similar spectrums of antimicrobial activity and less gastrointestinal adverse effects compared to erythromycin.  There is no data to support erythromycin as being either safer or more efficacious than other less expensive alternative antibiotics. Coverage will be considered for motility disorders. Treatment Alternatives: Doxycycline (F), azithromycin (F), minocycline (F), amoxicillin (F), cephalexin (F), clindamycin
(F), clarithromycin (F)
Medical Benefit Decisions
Drugs administered exclusively in the clinic setting are considered part of the medical benefit. These medications are
excluded from the Commercial Formulary and the Medicare Part D status defaults to Tier 4 unless excluded by CMS.
Drug Name: Nivolumab (Opdivo)
Dosage, Route: Vial, intravenous
Indication: Nivolumab monotherapy for the treatment of patients with
Reason for Review: New FDA-approved
advanced renal cell carcinomas (RCCs) who have received prior anti- indication under accelerated approval angiogenic therapy.
Decision: Update preservice coverage criteria
Commercial Medical Benefit
Medicare
Formulary Status Covered under the medical benefit, pre-service review
Covered under Part B required Not covered under the pharmacy benefit
Coverage Criteria:
Treatment of patients with unresectable or metastatic melanoma as a single agent
a. Covered in combination with CTLA-4 agents such as ipilimumab b. Not covered following progression on an alternative PD-1 agent such as pembrolizumab
Covered for NSCLC with progression on or after platinum-based chemotherapy. Patients with EGFR, ALK or ROS-1 gene
aberrations must have progressed on approved applicable agents.

Covered for advanced (metastatic or unresectable) renal cell carcinoma (RCC) after failure of at least one
antiangiogenic agent (e.g., sunitinib, pazopanib).

Rationale:
 Nivolumab is FDA approved for advanced RCC after receiving a prior antiangiogenic agent.
 Results from Phase 3 study CheckMate 025 (n=821) evaluated nivolumab for treatment of advanced RCC. Nivolumab
demonstrated superior overall survival (25.0 months vs 19.6 months) compared to everolimus. The objective response rate was significantly improved (25% vs 5%; P=.002) compared to everolimus.  Nivolumab had less frequent grade 3-4 adverse events (19% vs 37%) compared to everolimus.
Treatment Alternatives: Everolimus (F-PA), temsirolimus (MB), sorafenib (F-PA), axitinib (NF-PA), sunitinib (F-PA),
pazopanib (F-PA)
Drug Name: Elotuzumab (Empliciti)
Dosage, Route: Vial, intravenous
Indication: In combination with lenalidomide and dexamethasone, for
Reason for Review: Recent FDA accelerated
the treatment of patients with multiple myeloma who have received one to three prior therapies.
Decision: Add preservice coverage criteria
Commercial Medical Benefit
Medicare
Formulary Status Covered under the medical benefit, pre-service review
Covered under Part B required Not covered under the pharmacy benefit
Coverage Criteria:
Covered in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who
have received 1 prior therapy, and have demonstrated disease progression within 60 days of completion of the last
therapy. Additionally, patients must not be refractory to (progression while on therapy) immunomodulatory drug (IMiD)
(e.g., thalidomide, lenalidomide, pomalidomide).
Rationale:
 The FDA approval of elotuzumab, in combination with lenalidomide and dexamethasone, for the treatment of patients
with relapsed/refractory multiple myeloma was based on the Phase 3 ELOQUENT-2 trial demonstrating a modest improvement in progression-free survival of 4.5 months in patients treated with elotuzumab in combination with lenalidomide and dexamethasone versus lenalidomide plus dexamethasone alone [HR 0.7; 95% CI: 0.57 to 0.85; p=0.0004].  Patients treated with elotuzumab are at risk for infusion reactions. Common adverse reactions include fatigue, diarrhea, constipation, pyrexia, cough, peripheral neuropathy, and upper respiratory tract infections.  Cost is comparable to newer triplet multiple myeloma regimens that also include lenalidomide and dexamethasone.
 There is insufficient evidence at this time to suggest the ideal sequencing of treatment regimens for the different lines
of therapy for multiple myeloma. Elotuzumab may be considered for the treatment of patients with relapsed/refractory multiple myeloma, including patients with high-risk cytogenetics. Treatment Alternatives: Lenalidomide (F-PA), pomalidomide (NF), thalidomide (F-PA), bortezomib (MB), carfilzomib
(MB), ixazomib (NF), panobinostat (NF), daratumumab (MB)

Abbreviated Reviews
Approval
Indication and Alternatives
Formulary Decision
Rationale
New Drugs 10/21/2015 Patiromer Review at upcoming Alternatives: Sodium Medicare Part D: Tier 4 polystyrene sulfonate 12/11/2015 Alectinib Advanced ALK positive Review at upcoming NSCLC whose disease has relapsed after crizotinib Medicare Part D: Tier 5 (Xalkori) Alternatives: Ceritinib 11/20/2015 Ixazomib In combination with Review at upcoming lenalidomide and dexamethasone for the Medicare Part D: Tier 5 treatment of patients with multiple myeloma who have received at least one prior therapy Alternatives: Dexamethasone, carfilzomib, bortezomib 12/22/2015 Selexipag Pulmonary arterial Review at upcoming Alternatives: Ambrisentan, Medicare Part D: Tier 5 bosentan, macitentan, sildenafil, tadalafil, iloprost, treprostinil Chronic hepatitis C genotype Review at upcoming Medicare Part D: Tier 5 with Ledipasvir/sofosbuvir, Simeprevir in combination with sofosbuvir with/without ribavirin, paritaprevir/ritonavir/ombitasvir and dasabuvir Bipolar disorder and Review at upcoming Medicare Part D: Tier 4 Alternatives: Risperidone, quetiapine, olanzapine, ziprasidone, aripiprazole 12/11/2015 Uridine Emergency treatment of Review at upcoming adults and children who receive an overdose of Medicare Part D: Covered fluorouracil or capecitabine, or who develop certain severe or life-threatening toxicities within four days Alternatives: None Attention-deficit hyperactivity Commercial: Non-formulary Add criteria to match and add criteria methylphenidate ER suspension (Quillivant Medicare Part D: Tier 4 XR) for this new Methylphenidate IR, extended release methylphenidate ER, PA Criteria: Trial and failure stimulant dosage form dextroamphetamine IR, of all formulary preferred long- dextroamphetamine ER, acting medications for dextroamphetamine/ treatment of ADHD or inability to swallow tablets/capsules ST Criteria: Trial of a formulary preferred long-acting methylphenidate AND a long-acting amphetamine-salt based product. Methylphenidate Attention-deficit hyperactivity Commercial: Non-formulary Add criteria to match and add PA criteria methylphenidate ER suspension (Quillivant Medicare Part D: Tier 4 XR) for this new Methylphenidate IR, extended release methylphenidate ER, PA Criteria: Trial and failure stimulant dosage form. dextroamphetamine IR, of all formulary preferred long- dextroamphetamine ER, acting medications for dextroamphetamine/ treatment of ADHD or inability to swallow tablets/capsules ST Criteria: Trial of a formulary preferred long-acting methylphenidate AND a long-acting amphetamine-salt based product Chronic lymphocytic Commercial: Covered under Add criteria to match leukemia and indolent B-cell medical benefit; expand non-Hodgkin lymphoma existing preservice criteria to intravenous (Treanda) this new formulation Alternatives: Bendamustine approved intravenous When used to treat CLL, the following criteria apply:  Patients who have a contraindication or intolerance to one first-line therapy recommended by the NCCN guidelines (e.g. fludarabine-based therapy, obintuzumab+chlorambucil, rituximab+chlorambucil).  For the treatment of patients relapsed or refractory to one first-line therapy recommended by the NCCN guidelines (e.g. fludarabine-based therapy, obintuzumab+chlorambucil, rituximab+chlorambucil).  NOT be covered for use in patients with del(17p).
For other FDA-approved
indications, no restrictions
apply.

Medicare Part D: Covered
under Part B
New Indications 2/10/2016 Expanded indication to Commercial: Remain non- Review at upcoming include HCV genotype 1 formulary with PA criteria Medicare Part D: Remain tier Ledipasvir/sofosbuvir, Simeprevir in combination with sofosbuvir with/without ribavirin, paritaprevir/ritonavir/ombitasvir and dasabuvir Expanded indication for HCV Commercial: Remain Review at upcoming genotype 1 or 4 who are post formulary with PA criteria liver transplant without cirrhosis or with Medicare Part D: Remain tier compensated cirrhosis, and patients with HCV genotype 1 with decompensated cirrhosis Alternatives: Sofosbuvir, ribavirin, pegylated-interferon Treatment of adults with Commercial: Remain Review at upcoming active psoriatic arthritis and formulary with PA criteria treatment of adults with active ankylosing spondylitis Medicare Part D: Remain tier Alternatives: Ustekinumab, adalimumab, etanercept, infliximab Adults with progressive, well- Commercial: Remain Review at upcoming differentiated, non-functional formulary with PA criteria neuroendocrine tumors (NET) of gastrointestinal (GI) Medicare Part D: Remain tier or lung origin that are unresectable, locally advanced or metastatic. Alternatives: Octreotide, sunitinib, chemotherapy Treatment of hormone Commercial: Non-formulary Current criteria allows receptor (HR)-positive, with PA criteria use for expanded human epidermal growth factor receptor 2 (HER2)- PA Criteria: Patient with combination with anti- negative advanced or metastatic or locoregionally estrogen therapy. metastatic breast cancer in recurrent breast cancer not combination with fulvestrant amenable to curative intent in women with disease (i.e. surgery) in patients: progression following  With ER-positive and endocrine therapy. HER2-negative disease; Alternatives: Letrozole,  When used in anastrozole, fulvestrant, combination with some tamoxifen, exemestane type of anti-estrogen therapy (i.e., anastrozole, letrozole, or fulvestrant) Medicare Part D: Remain tier 5 Other Updates n/a Dupuytren's contracture, Commercial: Covered under Update criteria to peyronie's disease medical benefit and update remove "or during sexual intercourse" for Alternatives: Surgery Peyronie's disease, so Criteria for Peyronie's it will be independent  Diagnosis of Peyronie's dysfunction rider. disease for greater than or equal to 12 months in patients with stable disease. AND  Penile curvature of ≥30° and <90°, AND  Provider confirms treatment is medically necessary due to pain on
erection or during sexual
intercourse.
Medicare: Remain covered under Part B with criteria Treatment of genotype 1, 2, Commercial: Remain Update criteria to 3, or 4 chronic hepatitis C formulary and update PA clarify that genotype 3 (CHC) as a component of a use in combination combination antiviral with ribavirin for treatment regimen treatment duration of Treatment Duration: 24 weeks is only Ledipasvir/sofosbuvir,  In combination with patients who are ribavirin, pegylated-interferon interferon ineligible. pegylated-interferon: 12 weeks  In combination with ribavirin for
interferon ineligible
patients only: 24
weeks
 Decompensated cirrhosis awaiting liver transplant, in combination with ribavirin: up to 48 weeks Medicare: Remain tier 5 with PA Prevention of cardiovascular Commercial: Add generic to Generic rosuvastatin is disease, hyperlipidemia, formulary and change PA to familial hypercholesterolemia ST criteria once lower cost available soon. Adding generic is available Alternatives: Atorvastatin, simvastatin, pravastatin, PA Criteria: Failure, updating criteria lovastatin, ezetimibe contraindication, or intolerance of all equipotent availability and doses of formulary favorable pricing is alternatives (i.e., lovastatin, pravastatin, simvastatin,
atorvastatin)
ST Criteria: Trial of
atorvastatin

Medicare: Add generic to tier
1
Crohn's disease involving the Commercial: Remain non- Update criteria to allow ileum and/or ascending colon formulary and update PA for first line use in microscopic colitis Alternatives: Prednisone according to standard  Use in Crohn's and Microscopic Colitis for patients who have failed or are intolerant to prednisone  Use in microscopic
Medicare: Remain tier 5
FDA Safety Alerts
December 2015 through February 2016
ACTIONS TAKEN
Rosiglitazone-containing Diabetes Medicines: Drug Safety Communication -
FDA Eliminates the Risk Evaluation and Mitigation Strategy (REMS)
[Posted 12/16/2015] ISSUE: FDA is eliminating the Risk Evaluation and Mitigation Strategy (REMS) for
rosiglitazone-containing type 2 diabetes medicines, which are approved as
Avandia, Avandamet, Avandaryl, and generics. The REMS is no longer necessary
to ensure that the benefits of rosiglitazone medicines outweigh their risks. In 2013,
FDA required removal of the prescribing and dispensing restrictions for
rosiglitazone medicines after determining that data did not demonstrate an
increased risk of heart attack with rosiglitazone medicines compared to the
standard type 2 diabetes medicines metformin and sulfonylurea. FDA also required
the drug manufacturers to provide educational training to health care professionals
about the current state of knowledge regarding the heart risks of rosiglitazone
medicines. Manufacturers have since fulfilled these requirements. FDA has
continued monitoring these medicines and identified no new pertinent safety
information. FDA will update the public if any new information becomes available.
RECOMMENDATION: The REMS is no longer necessary to ensure that the
benefits of rosiglitazone medicines outweigh their risks.
FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for
diabetes to include warnings about too much acid in the blood and serious
urinary tract infections
[Posted 12-4-2015]
ISSUE: FDA previously issued a Drug Safety Communication in May 2015
warning about the risk of ketoacidosis with SGLT2 inhibitors and alerting that FDA
would continue to evaluate this safety issue. FDA review of the FDA Adverse
Event Reporting System (FAERS) database from March 2013 to May 2015
identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes treated
with SGLT2 inhibitors (see Data Summary). FAERS includes only reports
submitted to FDA, so there are likely additional cases about which we are
Drug Alert email developed for unaware. All patients required hospitalization or treatment in an emergency distribution via email to primary department. In many cases, ketoacidosis was not immediately recognized care, pharmacy, and because the blood glucose levels were below those typically expected for diabetic ketoacidosis. As a result, treatment of the ketoacidosis was delayed in some cases. FDA also identified 19 cases of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that started as urinary tract infections with the SGLT2 inhibitors reported to FAERS from March 2013 through October 2014. All 19 patients were hospitalized, and a few required admission to an intensive care unit or dialysis in order to treat kidney failure. As a result, FDA added new Warnings and Precautions to the labels of all SGLT2 inhibitors to describe these two safety issues, and to provide prescribing and monitoring recommendations. We are also requiring manufacturers of SGLT2 inhibitors to conduct a required postmarketing study. This required enhanced pharmacovigilance study requests that manufacturers perform analyses of spontaneous postmarketing reports of ketoacidosis in patients treated with SGLT2 inhibitors, including specialized follow-up to collect additional information, for a period of 5 years. RECOMMENDATION: No direct patient contact is necessary as this information is
already spelled out in the MediGuide that each patient receives. Drug Alert email
and EBRx article support provider education.
Noxafil (posaconazole): Drug Safety Communication - Dosing Errors when
Switching between Different Oral Formulations: Label Changes Approved
[Posted 1/4/2016] ISSUE: Posaconazole (POSA) is available as an intravenous solution as well as
both an oral suspension and a delayed-release tablet. The two POSA oral
formulations are not 1:1 interchangable as far as dosing is concerned due to
bioavailability. POSA has a notably increased bioavailabilty from the delayed-
release tablets respective of the suspension. As a result of multiple dosing errors
from ignorance to the differences, the FDA is having the outer carton, and the
Patient Information in the Drug Label changed to reinforce these differences. As
with all prescribing standards, we should require that drug, dosage form, strength,
frequency and administration route be included, and when information is missing,
pharmacists should seek clarification to prevent potential mistakes leading to
safety and or efficacy concerns.
RECOMMENDATION: EBRx article

Medical Policy Committee (MPC) Decision
Coverage criteria update for Hepatitis C medications to cover for all stages.
Hepatitis C Treatment Eligibility Criteria
Inclusion Criteria
 Patients with chronic hepatitis C virus (HCV). Chronic HCV is defined as a detectable viral load ≥ 6 months after initial detection of HCV RNA.  Patients with history of alcohol use disorder must be abstinent from alcohol use for 6 months or longer. Exceptions will be considered for patients who have abstained from alcohol for at least 3 months if they are: o Receiving treatment or under the care of an addiction medicine specialist; AND o Abstinence from alcohol during treatment  Patients with a history of intravenous (IV) drug use must be abstinent from IV drugs for at least 3 months. Patients with IV drug use within the last 3 months will be considered for treatment if they are: o Receiving opiate substitution therapy or receiving medication assisted treatment from an addiction medicine specialist or a buprenorphine-waived provider; AND o Abstinence from IV drug use during treatment
Exclusion Criteria
 Clinical y significant il ness or any other major medical disorder that may interfere with patients' ability to complete course of therapy or to benefit from therapy (e.g. undergoing treatment for advanced/metastatic oncology diagnosis, severe end organ disease not eligible for transplant).
Other Requirements
 Prescribed by or in consultation with a gastroenterologist, hepatologist, or infectious disease specialist.  Patient has been educated regarding antiviral therapy, risk factors for fibrosis progression, and the importance of adherence to treatment.  Both the treating clinician and the patient must be confident that the patient can effectively start and successfully adhere to treatment, and the clinician attests that he/she is confident in the patient's ability to maintain medication adherence.
Updates on Previous P&T Decisions
Medications reviewed at a previous P&T meeting.
Drug Name: Flibanserin (Addyi)
Dosage, Route: Tablet, oral
Indication: the treatment of premenopausal women with acquired,
Reason for Review: Recent FDA approval
generalized hypoactive sexual desire disorder (HSDD). Decision: Remain excluded, generally not covered for patients with sexual dysfunction rider with QL (coverage varies
based on plan)
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status Excluded with QL
Excluded with QL Quantity Limit
30 tablets per 30 days 30 tablets per 30 days Coverage Criteria: None
Medical Policy Committee (MPC) supports this decision.
Rationale:
 In the three pivotal clinical trials, flibanserin increased the number of satisfying sexual events (SSE) by an
additional 0.5 to 1 event per month and about 10% more women who received flibanserin reported meaningful improvement in their symptoms of hypoactive sexual desire disorder (HSDD) compared to women who were given placebo.  Due to the increased risk of severe hypotension and syncope with flibanserin and alcohol, flibanserin is available only through a restricted REMS Program. Most common adverse effects include dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth.  The cost of flibanserin per patient is high.  Flibanserin has been shown to cause modest improvements in HSDD symptoms in about a tenth of patients treated in pivotal trials. However, the clinical significance of these improvements may be largely subjective and difficult for patients to quantify. In addition, associated safety concerns may limit the number of patients that could be treated with this medication due to the contraindications with alcohol, CYP3A4 inhibitors, and liver dysfunction. Due to these efficacy and safety concerns as well high cost of treatment, flibanserin is considered not medically necessary. Treatment Alternatives: None
Drug Name: Alirocumab (Praluent)
Dosage, Route: Injection, subcutaneous
Indication: As an adjunct to diet and maximally tolerated statin therapy
Reason for Review: Recent FDA approval
for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of LDL-C. Decision: Do not add to formulary, add criteria, add QL
Closed Formulary
Open Formulary
Medicare Part D
Formulary Status NF with exception
Tier 3 with PA and QL Tier 5 (specialty) with PA Quantity Limit
1 syringe per 2 weeks 1 syringe per 2 weeks Coverage Criteria:
Heterozygous FH
 The patients is at least 18 years of age
 The patient has a diagnosis of HeFH based on genetic testing or a score of >8 on World Health Organization (WHO) diagnostic criteria  The medication is prescribed by, or in conjunction with, a specialist in cardiology or an endocrinologist with lipid management expertise  The patient failed to achieve an LDL-C <130 and meets one of the following : o Currently 90% adherent to maximally tolerated high-intensity statin therapy (i.e., atorvastatin 80mg or rosuvastatin 40mg) in combination with ezetimibe for at least 8 weeks o The patient has a documented contraindication to statin and ezetimibe therapy o The patient has a documented intolerance to statin therapy, as defined by the National Lipid Association  Maximally tolerated statin therapy is continued while receiving alirocumab therapy (unless not tolerated or contraindicated) Clinical ASCVD  The patients is at least 18 years of age  The patient has a diagnosis of clinical ASCVD evidenced of at least one of the following conditions: o Coronary heart disease (CHD), such as myocardial infarction (MI), angina, and coronary artery stenosis greater than 50% o Cerebrovascular disease, such as transient ischemic attack (TIA), ischemic stroke, and carotid artery stenosis greater than 50% o Peripheral artery disease, such as claudication  The medication is prescribed by, or in conjunction with, a specialist in cardiology  The patient failed to achieve an LDL-C <100 and meets one of the following : o Currently 90% adherent to maximally tolerated high-intensity statin therapy (i.e., atorvastatin 80mg or rosuvastatin 40mg) in combination with ezetimibe for at least 8 weeks o The patient has a documented contraindication to statin and ezetimibe therapy o The patient has a documented intolerance to statin therapy, as defined by the National Lipid Association  Maximally tolerated statin therapy is continued while receiving alirocumab therapy (unless not tolerated or contraindicated) Authorization will be reviewed after 6 and 12 months of therapy to confirm demonstration of continued clinical benefit, as demonstrated by LDL reduction since initiation of therapy with alirocumab. Medical Policy Committee (MPC) supports this decision and coverage criteria.
Rationale:
 Phase 3 clinical data demonstrated benefit for alirocumab over placebo in the primary endpoint of percentage
change in calculated LDL-C from baseline to week 24 in adults with HeFH or ASCVD who require additional lowering of LDL-C. In the absence of CV outcomes data, monotherapy with alirocumab would be inappropriate given the positive outcomes demonstrated with statins and ezetimibe.  Alirocumab appears to be relatively safe based on the data available, including treatment for up to 78 weeks. Longer studies are currently ongoing.  The phrase, ‘maximally tolerated statin doses', permits the use of PCSK9 agents for LDL-C reduction in ‘statin intolerant' ASCVD patients. This population represents about 14% of the patients identified as PCSK9-eligible in the U.S. labeling. Treatment Alternatives: Rosuvastatin (F-PA), atorvastatin, ezetimibe (F-PA)
Drug Name: Nivolumab (Opdivo)
Dosage, Route: Injection, intravenous
Indications: Nivolumab and ipilimumab combination treatment of
Reason for Review: New FDA approved
patients with unresectable or metastatic melanoma with BRAF V600 wild-type status, nivolumab monotherapy for advanced non-squamous Non-Small Cell Lung Cancer (NSCLC) that has progressed on or after platinum-based chemotherapy. Decision: Update preservice coverage criteria
Commercial Medical Benefit
Medicare
Formulary Status Covered under the medical benefit, pre-service review
Covered under Part B required Not covered under the pharmacy benefit Melanoma Coverage Criteria:
Treatment of patients with unresectable or metastatic melanoma:
a. Covered as monotherapy, except following progression on an alternative PD-1 agent such as pembrolizumab. b. Covered in combination with CTLA-4 agents such as ipilimumab in patients with ECOG score of 0 or 1, and have not progressed on a CTLA-4 agent such as ipilimumab or a PD-1 agent such as nivolumab or pembrolizumab Medical Policy Committee (MPC) supports coverage criteria.
NSCLC Coverage Criteria:
a. Covered for squamous NSCLC with progression on or after platinum-based chemotherapy.
b. Patients with EGFR, ALK, or ROS-1 gene aberrations must have progressed on approved applicable
Medical Policy Committee (MPC) rejected P&T coverage criteria decision to not cover nivolumab for non-
squamous NSCLC.

Renal Cell Carcinoma (RCC) Coverage Criteria: See above for March 2016 decision


Melanoma Rationale:
 Nivolumab in combination with ipilimumab is FDA approved in the first-line setting in patients with BRAF V600
wild-type melanoma.  Results from Phase 3 study CheckMate 067 (n=945) evaluated nivolumab-plus-ipilimumab in the first-line treatment setting for advanced melanoma. Nivolumab plus ipilimumab demonstrated significantly improved progression free survival (12 months vs. 7 months) with increased prevalence of adverse effects (e.g., immune-mediated adverse reactions) compared to nivolumab monotherapy. For advanced melanoma first-line therapy, nivolumab in combination with ipilimumab is a category 2A NCCN recommendation while nivolumab monotherapy is category 1. Cost for nivolumab in combination with ipilimumab is higher than nivolumab monotherapy. NSCLC Rationale:
 Nivolumab is FDA-approved for NSCLC that has progressed on or after platinum-based chemotherapy.
 A Phase 3 study demonstrated significantly improved overall survival (12 months vs. 9 months) compared to
docetaxel. Based on this evidence, the FDA indication was expanded to include non-squamous NSCLC in addition to squamous NSCLC.  While there have been no comparative studies for nivolumab vs. pembrolizumab for NSCLC, indirect comparison shows that response rate for both nivolumab and pembrolizumab has been about 20% without correction for PD-L1 status.  The NCCN guidelines for NSCLC recommend nivolumab (category 1, preferred) or pembrolizumab (category 2A) as second-line regimens after progression on doublet chemotherapy or bevacizumab.  Nivolumab and pembrolizumab have a similar safety profile, and are generally well tolerated.  The cost of nivolumab is similar to pembrolizumab. Treatment Alternatives: Pembrolizumab (MB), ipilimumab (MB), dabrafenib (F-PA), trametanib (F-PA)
Drug Name: Pembrolizumab (Keytruda)
Dosage, Route: Injection, intravenous
Indication: Treatment of patients with metastatic NSCLC whose tumors
Reason for Review: New FDA approved
express PD-L1 as determined by an FDA-approved test and who have disease progression on or after platinum-containing chemotherapy. Decision: Update pre-service coverage criteria
Commercial Medical Benefit
Medicare
Formulary Status Covered under the medical benefit, pre-service review
Covered under Part B required Not covered under the pharmacy benefit Coverage Criteria:
Covered for treatment of patients with unresectable or metastatic melanoma as a single agent at 2mg/kg every 3 weeks:
Patient must have progressed on ipilimumab and a BRAF inhibitor (if BRAF V600 mutation positive) Combination with CTLA-4 agents such as ipilimumab not covered Not covered following progression on alternative PD-L1 agent such as nivolumab Coverage Restriction: Not medically necessary for NSCLC.
Medical Policy Committee (MPC) supports this decision and coverage criteria.
Rationale:
 Results from one subset of the Phase 1 trial, KEYNOTE-001, led to FDA approval of pembrolizumab for NSCLC in
patients with tumor cells expressing PD-L1. This open label study examined overall response rate for pembrolizumab in patients with tumor cells expressing PD-L1 at various rates.  The percentage of neoplastic cells staining for membranous PD-L1 (proportion score) of >50% was selected as the cutoff using a training group (n=182). Within the validation group, 73 patients meeting the PD-cutoff >50% achieved overall response rate of 45.2%.  While there have been no comparative studies for pembrolizumab vs. nivolumab for NSCLC, indirect comparison shows that response rate for both nivolumab and pembrolizumab has been about 20% without correction for PD-L1 status.  The NCCN guidelines for NSCLC recommend nivolumab (category 1, preferred) or pembrolizumab (category 2A) as second-line regimens after progression on doublet chemotherapy or bevacizumab.  Pembrolizumab and nivolumab have a similar safety profile, and are generally well tolerated.  The cost of pembrolizumab and nivolumab are similar. Treatment Alternatives: Nivolumab (MB), docetaxel (MB), erlotinib (F-PA), gemcitabine (MB)
Drug Name: Brentuximab vendotin (Adcetris)
Dosage, Route: Injection, intravenous
Indication: Brentuximab is an antibody-drug conjugate previously FDA
Reason for Review: New FDA approved
approved for classical Hodgkin lymphoma (HL) after failure of autologous indication
hematopoietic stem cell transplantation (HSCT) or after failure of at least
two prior multi-agent chemotherapy regimens in patients who are not
auto-HSCT candidates. Brentuximab was also previously FDA approved
for systemic anaplastic large cell lymphoma (sALCL) after failure of at
least one prior multi-agent chemotherapy regimen.
Decision: Do not update pre-service coverage criteria
Commercial Medical Benefit
Medicare
Formulary Status Covered under the medical benefit, pre-service review
Covered under Part B required Not covered under the pharmacy benefit Coverage Restriction:
1. For the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or failure of at
least two prior multi agent chemotherapy regimens in patients who are not autologous stem cell transplant candidates OR 2. For the treatment of patients with systemic anaplastic large cell lymphoma after failure of at least one prior multi- agent chemotherapy regimen Medical Policy Committee (MPC) supports this decision.
Rationale:
 The Phase 3 AETHERA trial examined 329 Hodgkin lymphoma (HL) patients at high risk for progression post
autologous hematopoietic stem cell transplant (i.e., disease refractory to front line therapy, relapsed disease <12 months after therapy, and pre-existing extranodal involvement). Results showed that early consolidation with brentuximab was associated with significantly improved progression free survival (3.5 years) vs. placebo (2 years) across all risk groups.  Brentuximab has a black box warning for progressive multifocal leukoencephalopathy (PML), but there were no instances reported in the AETHERA trial. Without demonstrated overall survival benefit, the value of high cost brentuximab for prevention of progression is not established. Treatment Alternatives: None

Source: https://provider.ghc.org/open/providerCommunications/highlights/march-2016.pdf