Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at The October to December 2012 DEC Meetings

The Drug Evaluation Committee (DEC) of Express Scripts Canada conducts monthly reviews of all new drugs receiving their Notice of Compliance from Health Canada , to ascertain their place in therapy and their possible impact on the private payer sector. The prices quoted in this document are approximations for general information purposes only, and are not intended, nor should they be relied upon, for purposes of any actual claims adjudication or reimbursement. This publication, describing new drugs of significance, is provided to our customers on a quarterly basis as a value-added service. We hope that you will find this Health Newsflash informative, timely, and useful.

NEW DRUGS

Esbriet (pirfenidone)

Dosage Form Capsule

DIN & Strength 02393751 – 267mg

Manufacturer Intermune International AG

AHFS Class 48:92.00 – Respiratory Tract Agents, Misc

Indication(s) Esbriet (pirfenidone) is indicated for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) in adults. Dose The recommended daily dose is 2,403mg/day. Therapeutic Alternatives None Clinical Notes Esbriet (pirfenidone) is the first drug indicated for the treatment of IPF. Although its exact mechanism of action is not known, it is thought to have antifibrobitic and anti-inflammatory properties. Its effect on IPF is postulated to be due to attenuation of fibroblast proliferation, production of fibrosis-association proteins and cytokines IPF is a chronic, progressive and debilitating disease that is associated with a progressive and irreversible decline in lung function both objectively and subjectively. The median survival after diagnosis is estimated at two to three years with the majority of patients dying from progressive lung disease. The only recommended therapies are long-term oxygen therapy to treat resting hypoxemia and lung transplantation for eligible patients. There are no pharmacologic therapies available that have shown evidence of efficacy. Pirfenidone is also under investigation in other disorders such as multiple sclerosis, familial adenomatous polyposis, and neurofibromatosis type 1. Place in Therapy Pirfenidone is the first pharmacologic treatment indicated for the treatment of IPF. The treatment effects are modest; however, no other treatment has been proven to be efficacious for this disease.

October 2012

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

Comparative Pricing

Esbriet Unit cost $13.47 Annual cost $44,000

Impact/ Plan Management Suggestions Esbriet is the first medication to be approved for the treatment of IPF. Because this drug is being studied for other possible uses, and due to its high cost, it is recommended that this drug be managed with a Prior Authorization program to ensure appropriate utilization.

Potiga (retigabine) Dosage Form Tablet

DIN & Strength 02394944 – 50mg 02394960 – 100mg 02394979 – 200mg 02394987 – 300mg 02394995 – 400mg

Manufacturer GlaxoSmithKline Inc

AHFS Class 28:12.92 – Miscellaneous Anticonvulsants

Indication(s) *Canadian Product Monograph not available; information from US FDA Prescribing Information* Potiga is indicated as adjunctive treatment of partial-onset seizures in patients aged 18 years and older. Dose Dosage ranges from 300mg to 1,200mg per day usually given three times daily. Therapeutic Alternatives Frisium (clobazam)*; Neurontin (gabapentin)*; Vimpat (lacosamide); Trileptal (oxcarbazepine)*; phenobarbital*; primidone*; Topamax (topiramate)*; Depakene/Epival (valproic acid/divalproex sodium)*; Sabril (vigabatrin) * generics available Clinical Notes The pharmacological profile of retigabine is different from currently approved anti-epileptic drugs (AEDs). The primary mode of action of retigabine is at KCNQ (Kv7) ion channels. Current agents have minimal to no effects on neuronal potassium gated channels; although it is known that these channels play a major role in the control of neuronal excitability. Retigabine is the first neuronal potassium channel opener developed for the treatment of epilepsy. A further reported pharmacological activity of retigabine is the augmentation of gamma-aminobutyric acid (GABA) mediated neurotransmission, a mechanism of action thought to contribute to the efficacy of a number of other AEDs. However, the relevance of these GABA effects to the observed anticonvulsant efficacy of retigabine in vivo has not been established. The efficacy of retigabine was established in three pivotal placebo-controlled, randomized clinical trials in patients with uncontrolled epilepsy taking one to three other AEDs. The most commonly reported adverse effects associated with retigabine use were CNS related: dizziness, somnolence, and fatigue. Infrequent but potentially more serious effects were urinary retention, urinary crystal formation, slight and transient increase in QT interval, and liver enzyme elevation. Overall, the drug was well tolerated.

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October 2012

Place in Therapy Due to its unique mechanism of action, retigabine offers a potentially effective adjunctive treatment for patients whose seizures are uncontrolled on other therapy. Comparative Pricing Potiga Vimpat Apo-Gabapentin

Unit cost Price not available range from

$2.44 to $5.59 (50mg to 200mg)

range from $0.11 to $1.74

(100mg to 800mg) Annual cost Price not available $1,800-$4,000 $300-$2,250 Impact/Plan Management Suggestions Insufficient information

Stribild (elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate) Dosage Form Tablet

DIN & Strength 02397137 – 150/150/200/300mg

Manufacturer Gilead Sciences Canada Inc

AHFS Class 08:18.08 – Antiretroviral agent

Indication(s) Stribild is indicated as a complete regimen for the treatment of HIV-1 infection in adults who are antiretroviral treatment-naïve. Dose The recommended dose of Stribild is one tablet taken orally once daily. Therapeutic Alternatives Atripla (efavirenz/emtricitabine/tenofovir disoproxil fumarate); Complera (emtricitabine/rilpivirine/tenofovir disoproxil fumarate); other combination therapies (at least two tablet/capsule combinations). Clinical Notes Stribild is a fixed-dose combination tablet containing elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate (DF). Each tablet contains 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 300 mg of tenofovir DF (equivalent to 245 mg of tenofovir disoproxil). Elvitegravir is a novel HIV-1 integrase strand transfer inhibitor (INSTI). Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A family, which pharmacokinetically enhances the activity of elvitegravir. Tenofovir DF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5�-monophosphate. Emtricitabine is a synthetic nucleoside analog of cytidine. Tenofovir and emtricitabine are both considered to be nucleoside reverse transcriptase inhibitors (NRTIs). The 2012 HIV guidelines recommend a combination antiretroviral therapy (ART) regimen generally consisting of two NRTIs + one active drug from one of the following classes: non-nucleoside reverse transcriptase inhibitors, protease inhibitors (generally boosted with RTV), INSTI, or a CCR5 antagonist. Selection of a regimen should be individualized on the basis of virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance testing results, and the patient’s comorbid conditions.

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

Place in Therapy Stribild is recommended as a possible alternative regimen for ART-naïve HIV-infected patients with adequate kidney function (i.e., no worse than moderate kidney dysfunction). Pricing Stribild Atripla Complera Unit cost $48.02 $43.47 $42.45 Annual cost $17,500 $15,900 $15,500 Impact/Plan Management Suggestions Minimal impact. It is recommended to manage claims for this drug similar to other combination HIV-1 treatments since it is priced in line with alternative therapies.

Kalydeco (ivacaftor) Dosage Form Tablet

DIN & Strength 02397412 – 150mg

Manufacturer Vertex Pharmaceuticals (Canada) Incorporated

AHFS Class 48:92.00 – Respiratory agents, miscellaneous

Indication(s) Kalydeco is indicated for the treatment of cystic fibrosis (CF) in patients age 6 years and older who have a G551D mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Dose The recommended dose for adults and children ≥ 6 years is 150 mg taken orally every 12 hours (300 mg total daily dose). Therapeutic Alternatives None. Other treatments for CF associated symptoms and complications should be used and continued as required. Clinical Notes Cystic fibrosis (CF) is a multisystem disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, located on chromosome 7. This genetic defect inhibits appropriate salt and water movement through various tissues causing mucous lining the lungs and other tissues to become thick and sticky. Lung disease is the leading cause of morbidity and mortality in patients with CF. Ivacaftor is a small molecular weight oral drug that is specifically designed to treat patients who have a G551D mutation in at least one of their CFTR genes. The G551D mutation, which occurs in approximately 5 percent of CF patients, impairs the regulated activation of the ion channel that is formed by the CFTR protein. Ivacaftor was developed to increase chloride ion flux in cells expressing G551D CFTR. Ivacaftor potentiates epithelial cell chloride ion transport of defective (G551D mutant) cell-surface CFTR protein thereby improving the regulation of salt and water absorption and secretion in various tissues (eg, lung, gastrointestinal tract).

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

Place in Therapy Kalydeco is recommended for use in all CF patients 6 years and older who carry at least one copy of the G551D CFTR mutation. It is not known if this drug will be effective in patients with other mutations that affect CFTR channel activation. Ivacaftor monotherapy appears to be ineffective in patients who are homozygous for delta F508 (F508del), the most common CFTR mutation. Pricing Kalydeco Unit cost $445 Annual cost $325,000 Impact/Plan Management Suggestions Intermediate impact – very high cost drug therapy for a small subset of patients with a rare disease. Recommend use of Prior Authorization to ensure drug used for indicated purpose in patients with the required genetic mutation.

NEW FORMULATION

Seebri Breezhaler (glycopyrronium bromide)

Dosage Form Capsule for inhalation (dry powder inhaler)

DIN & Strength 02394936 - 50µg/capsule

Manufacturer Novartis Pharmaceuticals Canada Inc

AHFS Class 12:08.08 - Antimuscarinics

Indication(s) *Canadian Product Monograph not available; information from European Medicines Agency Summary of Product Characteristics* Seebri Breezhaler is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dose The recommended dose is the inhalation of the contents of one capsule once daily using the Seebri Breezhaler inhaler. Therapeutic Alternatives Spiriva (tiotropium bromide); Onbrez Breezhaler (indacaterol maleate) Clinical Notes Seebri Breezhaler contains glycopyrronium bromide, a quaternary ammonium anticholinergic bronchodilator. When Seebri Breezhaler is inhaled, it causes the muscles of the airways to relax, helping to keep the airways open and allowing the patient to breathe more easily. The chemistry of this compound keeps the effects local with little CNS side effects. Glycopyrronium is the same chemical compound as glycopyrrolate (Robinul®). Glycopyrronium bromide has been shown in early stage clinical trials to provide sustained 24 hour bronchodilation with a rapid onset of action.

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

Place in Therapy From the information currently available, Seebri Breezhaler would appear to be an effective and well tolerated bronchodilator which provides comparable clinical benefits with respect to improvement of exercise tolerance and respiratory function as other long-acting bronchodilators such as tiotropium and indacaterol. Comparative Pricing Seebri Breezhaler Spiriva Handihaler Onbrez Breezhaler Unit cost Price not available $2.21/18µg capsule $2.21/75µg capsule Annual cost Price not available $800 $800 Impact/Plan Management Suggestions Insufficient information.

NEW DRUG COMBINATION

Edarbyclor (azilsartan medoxomil/chlorthalidone) Dosage Form Tablet

DIN & Strength 02397749 – 40mg/12.5mg 02397757 – 80mg/12.5mg 02397765 – 40mg/25mg

Manufacturer Takeda Canada Inc.

AHFS Class 24:32.08 – Angiotensin II AT1 Receptor Blocker

Indication(s) *Canadian Product Monograph not available: information from US Prescribing Information* Edarbyclor contains an angiotensin II receptor blocker (ARB) and a thiazide-like diuretic and is indicated for the treatment of hypertension, to lower blood pressure. Edarbyclor may be used in patients whose blood pressure is not adequately controlled on monotherapy. Edarbyclor may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Dose The recommended starting dose of Edarbyclor is 40/12.5 mg taken orally once daily. Most of the antihypertensive effect is apparent within 1 to 2 weeks. The dosage may be increased to 40/25 mg after 2 to 4 weeks as needed to achieve blood pressure goals. Therapeutic Alternatives Atacand Plus (candesartan/HCT)*; Teveten Plus (eprosartan/HCT); Avalide (irbesartan/HCT)*; Hyzaar (losartan/HCT)*; Micardis Plus (telmisartan/HCT)*: Diovan HCT (valsartan/HCT)*; Olmetec Plus (olmesartan/HCT) * generic available

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

Clinical Notes Edarbyclor is a fixed dose combination of an ARB, azilsartan medoxomil and a thiazide-type diuretic, chlorthalidone. The combination of these two drugs has been shown to lower both systolic and diastolic blood pressures by greater amounts than each drug alone. Several fixed-combination antihypertensive agents exist. Edarbi is unique in that it is the only combination drug that contains an ARB with the long-acting thiazide-type diuretic, chlorthalidone. Although no prospective, randomized trials assessing cardiovascular outcomes between the two have been conducted, evidence indicates that chlorthalidone may be superior to hydrochlorothiazide. The Multiple Risk Factor Intervention Trial (MRFIT) was first to propose a clinical benefit with chlorthalidone compared to hydrochlorothiazide. Suggested benefits of combination therapy compared to monotherapy include increased BP control by different mechanisms of action, lower dosing requirements, and fewer adverse events. Another advantage to consider with combination therapy is the added benefit of fixed combination drugs. Fixed combination drugs have the ability to simplify complex medication regimens, increase adherence, and be more cost effective than their separate parts. Place in Therapy Edarbyclor is a fixed-dose combination of the ARB, azilsartan, and the diuretic, chlorthalidone. This combination may be used for patients whose blood pressure is not controlled by monotherapy with either agent or as initial therapy in those patients whose blood pressure is unlikely to be controlled by single agent therapy. Comparative Pricing

Edarbyclor Olmetec Plus Teva-Irbesartan/HCT Unit cost Price not available $1.02 $0.30 Estimated cost per Course of Treatment Price not available $370 $110

Impact/Plan Management Suggestions Insufficient information.

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

FIRST TIME GENERICS First-Time Generic Drugs (Notices of Compliance from Aug 30, 2012 to Dec 5, 2012)

Generic Name Reference Drug

(Brand)

Rank by ingredient

cost in 2011

Manufacturer Route of Administration

Approved Indications

Lamivudine HBV Heptovir 411 Apotex Incorporated

Oral Chronic Hepatitis B infection

Candesartan/HCTZ Atacand Plus

-- Apotex Incorporated

Oral High blood pressure

Riluzole Rilutek 469

Apotex Incorporated

Oral Amyotrophic lateral sclerosis (ALS, “Lou Gehrig’s Disease”)

Olopatadine Patanol 162 Sandoz Canada Incorporated

Ophthalmic Allergic conjunctivitis

Sildenafil Viagra 99 Various Oral Erectile dysfunction

Entecavir Baraclude 295 Apotex Incorporated

Oral Chronic Hepatitis B infection

Oxycodone CR* OxyContin 23 Various Oral Chronic pain * recommend additional management strategies (e.g., prior authorization, temporal claims limits) to minimize misuse or diversion.

PRODUCT LINE-EXTENSION Product Line-Extension (Notices of Compliance from Aug 30, 2012 to Dec 5, 2012)

Brand name

Chemical name Manufacturer Dosage form Type of Line Extension

Specifics/Comments

Inspra Eplerenone Pfizer Canada Inc.

Tablet New indication

To reduce the risk of cardiovascular mortality and hospitalization for heart failure in patients with NYHA class II systolic chronic heart failure and left ventricular systolic dysfunction

Prezista Darunavir ethanolate Janssen Inc Tablet New strength 800mg Januvia Sitagliptin phosphate

monohydrate Merck Canada Inc

Tablet New indication

Indicated for use in combination with pioglitazone or metformin + pioglitazone

Janumet Sitagliptin/Metformin Merck Canada Inc

Tablet New indication

Indicated for use in combination with pioglitazone

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the October to December 2012 DEC Meetings

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October 2012

October 2012

PRODUCT LINE-EXTENSION

Product Line-Extension (Notices of Compliance from Aug 30, 2012 to Dec 5, 2012) Brand name

Chemical name Manufacturer Dosage form Type of Line Extension

Specifics/Comments

Intelence Etraverine Janssen Inc Tablet New strength, New indication

25mg Use in treatment experienced pediatric patients 6 years to 18 years of age.

Herceptin Trastuzumab Hoffmann La Roche Limited

Intravenous injection

New indication

Early stage breast cancer indication extended to use following adjuvant chemotherapy consisting of doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel; use in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin

Epuris Isotretinoin Cipher Pharmaceuticals Inc

Capsule New brand Therapeutically similar to Accutane Roche and Clarus, although not interchangeable with these

Humira Adalimumab Abbvie Corporation

Subcutaneous injection

New indication, Manufacturer name change

Polyarticular Juvenile Idiopathic Arthritis

Prolia Denosumab Amgen Canada Inc

Subcutaneous injection

New indication

For use in men with osteoporosis

Eliquis Apixaban Bristol Myers Squibb Canada

Tablet New strength, New indication

5mg For prevention of stroke and systemic embolism in patients with atrial fibrillation.

Health Newsflash — a Quarterly Publication New Drugs and Pipeline News Reviewed at the July to September 2012 DEC Meetings

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