Health Newsflash A Quarterly Publication

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1 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 Carbaglu (carglumic acid) Tablet mg Orphan Europe S.A.R.L. 40:10.00 Ammonia Detoxicants *Canadian Product Monograph not available; information from Health Canada Summary Basis for Decision (SBD) for Carbaglu and European Medicines Agency (EMeA) Summary of Product Characteristics (SmPC)* Carbaglu is indicated for: Acute hyperammonemia in patients with NAGS deficiency: Carbaglu is indicated as an adjunctive therapy in pediatric and adult patients for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme NAGS. During acute hyperammonemic episodes, concomitant administration of Carbaglu with other ammonia lowering therapies such as alternate pathway medications, hemodialysis, and dietary protein restriction are recommended. Maintenance therapy for chronic hyperammonemia in patients with NAGS deficiency: Carbaglu is indicated for maintenance therapy in pediatric and adult patients for chronic hyperammonemia due to the deficiency of the hepatic enzyme NAGS. During maintenance therapy, the concomitant use of other ammonia lowering therapies and protein restriction may be reduced or discontinued based on plasma ammonia levels. Based on clinical experience, the treatment may be started as early as the first day of life or upon hyperammonemia. The initial daily dose should be 100 mg/kg, up to 250 mg/kg if necessary. It should then be adjusted individually in order to maintain normal ammonia plasma levels. N/A Page 1 of 20 Q2 2015

2 Carbaglu is indicated for the treatment of hyperammonemia associated with N-acetylglutamate synthase deficiency. It is presented as a dispersible tablet containing 200 mg of carglumic acid (N-carbamoyl-L-glutamic acid, NCGA). N-acetylglutamate synthase (NAGS) deficiency is a very rare inborn error of metabolism. NAGS deficiency, which is the rarest congenital urea cycle disorder, results in a severe defect of ammonia detoxification with a rapid lethal course in most cases. The estimated worldwide prevalence of NAGS deficiency is < 1 in 1,000,000. In NAGS deficiency, the production of N-acetylglutamate (NAG) is impaired. Carglumic acid (N-carbamoyl-L-glutamic acid, NCGA) which is an aminoacid analogue of NAG, although being in vitro a weaker activator of carbamoyl phosphate synthetase (CPS) than the naturally occurring activator NAG, was shown in vivo to reach the mitochondrion more easily than NAG. Carbaglu thus replaces NAG for the activation of CPS where NAG is lacking due to the deficiency of the enzyme responsible for its synthesis (NAGS). Carbaglu is the only adjunctive pharmacologic therapy for the treatment of NAGS deficiency. Due to the nature of these disorders, treatment is expected to be required for life. Comparative Pricing Price not available Insufficient information Page 2 of 20 Q2 2015

3 Cosentyx (secukinumab) Subcutaneous injection mg (powder for solution) mg/ml (solution) Novartis Pharmaceuticals Canada Inc. 84:92.00 Misc. Skin and Mucous Membrane Agents Cosentyx (secukinumab) is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. The recommended dose is 300 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg. Traditional: methotrexate*; Neoral (cyclosporine)*; Soriatane (acitretin); Specialty: Humira (adalimumab); Enbrel (etanercept); Stelara (ustekinumab); Remicade (infliximab); Inflectra (infliximab); Otezla (apremilast) *generics available Psoriasis is one of the most common human skin diseases affecting 1.7% of the general Canadian population representing more than 500,000 individuals. It is a complex disorder, characterized by inflammation, increased keratinocyte hyperproliferation, and altered epidermal differentiation. Psoriasis has significant negative impact on the global well-being of patients and people living with them. Patients with moderate to severe disease represent approximately 15% to 25% of plaque psoriasis patients and generally require systemic therapy. Cosentyx (secukinumab) is a first in class fully human monoclonal antibody which selectively binds and neutralizes the proinflammatory cytokine interleukin-17a (IL-17A). This new mechanism of action leads to the normalization of skin histology, including achievement of clear to almost clear skin for the majority of patients. This drug s specificity offers the potential for fewer off target effects when compared to other currently available treatment options. Cosentyx has been evaluated in an extensive clinical program for the treatment of patients with moderate to severe plaque psoriasis. As the first in class, new mode of action product, specifically neutralizing IL-17A, Cosentyx provides an important addition to existing treatment options for this serious disease. Page 3 of 20 Q2 2015

4 Comparative Pricing Drug Estimated annual cost (maintenance ) Cosentyx $21,000 Enbrel $21,500 Humira $20,500 Remicade $28,000* Stelara $21,000 Otezla $15,000 *based on 70kg body weight; after treatment induction. Intermediate impact. Potential cost shift. Utilization managed through prior authorization. Page 4 of 20 Q2 2015

5 Duaklir TM Genuair (formoterol fumarate dehydrate / aclidinium bromide) Dry powder inhaler mcg / 400mcg / inhaler AstraZeneca Canada Inc. 12:12.08 Beta-Adrenergic Agonists Duaklir Genuair (aclidinium bromide/formoterol fumarate dihydrate) is a combination of a longacting muscarinic antagonist (LAMA) and a long-acting beta2-agonist (LABA) indicated as a long-term maintenance bronchodilator treatment for airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. The recommended dose is one inhalation of Duaklir Genuair twice daily. Anoro Ellipta (umeclidinium/vilanterol); Ultibro Breezhaler (glycopyrronium/ indacaterol) The two active substances in Duaklir Genuair, aclinidium bromide and formoterol fumarate dihydrate, work by keeping the airways open and allowing the patient to breathe more easily. Aclidinium bromide is a long-acting muscarinic antagonist (LAMA). This means that it widens the airways by blocking some receptors in muscle cells in the lungs called muscarinic (also known as cholinergic) receptors, which control the contraction of muscles. When aclidinium bromide 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. Formoterol is a long-acting beta-2 agonist (LABA). It works by attaching to receptors known as beta-2 receptors found in the muscles of the airways. When it attaches to these receptors, it causes the muscles to relax, which keeps the airways open and helps with the patient s breathing. Long-acting muscarinic antagonists and long-acting beta-2 agonists may be combined in the management of COPD in those individuals for whom monotherapy with a long acting bronchodilator is not sufficient to control symptoms. Duaklir Genuair becomes the third combination LAMA/LABA product available for management of COPD. Duaklir requires twice daily administration while Anoro Ellipta and Ultibro Breezhaler are used only once daily. The Genuair device is unique and provides a visual and aural confirmation of successful dose administration. Page 5 of 20 Q2 2015

6 Pricing Drug Estimated annual cost Duaklir Genuair $950 Anoro Ellipta $1,100 Ultibro Breezhaler $1,100 Minimal impact. Cost shift from other drugs with similar costs. Page 6 of 20 Q2 2015

7 Fetzima (levomilnacipran) Extended Release Capsule mg mg mg mg Actavis Specialty Pharmaceuticals Co. Actavis Specialty Pharmaceuticals Co. Fetzima (levominacipran extended-release capsules) is indicated for the treatment of major depressive disorder (MDD) in adults. The recommended dose range for Fetzima is 40 mg to 120 mg once daily. Effexor XR (venlafaxine)*; Pristiq (desvenlafaxine); Cymbalta (duloxetine) *generics available Fetzima (levomilnacipran) is a novel serotonin and norepinephrine reuptake inhibitor (SNRI) for the treatment of major depressive disorder. The drug differs from previously available SNRIs in having twice the potency for norepinephrine versus serotonin reuptake inhibition. In four of the six short-term clinical trials, levomilnacipran was statistically significantly more efficacious than placebo. The only available relapse prevention study did not show reduction any difference in time to relapse, perhaps because relapse rates were low. The most common adverse events occurring twice as often as on placebo were nausea, excessive sweating, constipation, rapid heart rate, vomiting, erectile dysfunction, palpitations, and ejaculation disorder. In a few patients, hypertension or orthostatic hypotension may occur. There are no trials available that compare levomilnacipran to other antidepressants. Fetzima is the fourth SNRI antidepressant to become available for the treatment of MDD. Pricing Drug Estimated treatment cost Fetzima Price not available Mylan-Venlafaxine XR $ Pristiq $1,100 Cymbalta $750-$3,000 Insufficient information Page 7 of 20 Q2 2015

8 Iclusig (ponatinib hydrochloride) Tablet mg mg Ariad Pharmaceuticals Inc. 10:00.00 Antineoplastic agents Iclusig is indicated for the treatment of adult patients with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom other tyrosine kinase inhibitor (TKI) therapy is not appropriate, including CML or Ph+ ALL that is T315I mutation positive or where there is prior TKI resistance or intolerance. [Conditional marketing approval, NOC/c] The recommended starting dose is 45 mg of ponatinib once daily. Consider reducing the dose from 45mg once daily to 15mg once daily for CP-CML patients who have achieved a major cytologenetic response (MCyR). Treatment should be continued as long as the patient does not show evidence of disease progression or unacceptable toxicity. Consider discontinuing ponatinib if a complete haematologic response has not occurred by 3 months (90 days). N/A Iclusig is third/fourth line therapy when other available alternatives have failed. Chronic myeloid leukaemia (CML) is a slowly progressing disease in which too many white blood cells are made in the bone marrow. It represents about 15% to 20% of adult leukaemias. The underlying cause of CML is the BCR-ABL fusion oncoprotein, which results from a chromosomal translocation in blood stem cells. This chromosomal abnormality, known as the Philadelphia chromosome (Ph+), is present in about 95% of all patients with CML, as well as about 20% to 25% of adult patients with acute lymphoblastic leukaemia (ALL). Chronic myeloid leukaemia is typically a triphasic continuum of disease with a chronic phase (CP-CML), accelerated phase (AP-CML), and blast phase (BP-CML) characteristics of the disease and prognosis are different for each phase. Chronic is the longest phase, and can last over 10 years in some patients. However, if transition to AP-CML occurs, median survival is typically limited to under a year, while patients in BP-CML (which resembles acute leukaemia) usually live for only a few months. Most patients are diagnosed in CP-CML and may be asymptomatic or present with fatigue, anaemia, weight loss, night sweats, or an enlarged spleen. Acute lymphoblastic leukaemia (ALL) is a malignant proliferation of lymphoid cells. The majority of cases of ALL show chromosomal and genetic abnormalities, and approximately 25% of adult cases of ALL are Ph+. The presence of the BCR-ABL translocation confers an adverse prognosis. The usual first-line therapy for Ph+ associated leukemias are the tyrosine kinase inhibitors (TKIs) with imatinib being established as first-line and second-line treatments being the newer TKIs such as dasatinib and nilotinib. Resistance to these TKIs can be problematic in some patients. Often this resistance is associated with mutation on the BCR-ABL gene designated as T315I, which is associated with resistance to the three aforementioned TKIs. Ponatinib is a tyrosine kinase inhibitor, designed with the purpose of potently inhibiting the kinase activity of native BCR-ABL, and all mutant variants, including gatekeeper T315I. Controlled Distribution Program Prescribers must become certified through the Iclusig Controlled Distribution Program prior to prescribing Iclusig. Iclusig is only available through pharmacies that agree to follow the Iclusig Controlled Distribution Program requirements. Page 8 of 20 Q2 2015

9 Iclusig is second- or third-line TKI therapy for patients in all phases of CML and ALL with failure to first- or second-line TKIs such as imatinib, dasatinib or nilotinib. Comparative Pricing Drug Estimated monthly cost Iclusig $10,000 Teva-Imatinib $800-$1,200 Sprycel $4,900-$5,300 Tasigna $1,800-$2,500 High impact. Manage with Prior Authorization to ensure appropriate utilization. Page 9 of 20 Q2 2015

10 Keytruda (pembrolizumab) Intravenous injection mg Vial Merck Canada Inc. 10:00.00 Antineoplastic agents Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab therapy and, if BRAF V600 mutation positive, following a BRAF or MEK inhibitor. [Conditional marketing approval, NOC/c] The recommended dose of Keytruda is 2 mg/kg administered intravenously over 30 minutes every 3 weeks. Patients should be treated with Keytruda until disease progression or unacceptable toxicity. None prior therapies include: immunotherapy: Yervoy (ipilimumab); BRAF/MEK inhibitors: Zelboraf (vemurafenib); Tafinlar (dabrafenib); Mekinist (trametinib) Keytruda (pembrolizumab) is a selective humanized monoclonal antibody designed to block the interaction between programmed cell death receptor-1 (PD-1) and its ligands, PD-L1 and PD-L2. The PD-1 pathway is an immune control checkpoint that may be engaged by tumour cells to inhibit active T-cell immune surveillance. By inhibiting the PD-1 receptor from binding to its ligands, Keytruda reactivates tumour-specific cytotoxic T lymphocytes in the tumour microenvironment and thereby also reactivates anti-tumour immunity. Pembrolizumab provided a significant level of response in patients who have progressed following treatment with ipilimumab in a Phase I trial. Responses appear to be durable in these patients with median duration of response not reached after eight month median follow-up. This led to conditional approval of this drug. Keytruda provides a treatment alternative in patients with unresectable or metastatic melanoma who have no other viable treatment alternatives. Comparative Pricing Drug Estimated cost per month / cycle Keytruda $6,600 (3 weeks) Yervoy $24,360 (3 weeks, maximum treatment of four cycles) Zelboraf $12,000 Tarfinlar $8,000 Mekinist $9,200 Mekinist + Tafinlar $17,200 High impact. Manage with Prior Authorization to ensure appropriate utilization. Page 10 of 20 Q2 2015

11 Prolensa (bromfenac sodium sesquihydrate) Ophthalmic solution % Bausch & Lomb Inc. 52:08:20 Eye, Ear, Nose and Throat Non-Steroidal Anti-Inflammatory Agents Prolensa is indicated for treatment of pain and inflammation associated with cataract surgery. Instil 1 drop into affected eye(s) once daily beginning one day prior to surgery and continuing on the day of surgery and for two weeks postoperatively. Ketorolac 0.5% (various generics), Voltaren Opththa 0.1% (and generics), Ilevro 0.3%, Nevanac 0.1% Prolensa provides powerful and rapid resolution of inflammation and pain by leveraging the unique potency of the bromfenac molecule in a formulation designed to facilitate ocular penetration. The advanced formulation allows for a lower concentration of bromfenac in a once daily dosing regimen. Prolensa is a solution that does not require shaking to deliver a consistent dose in each drop. Prolensa is another option for patients requiring ophthalmic analgesia post-cataract surgery. Comparative Pricing Drug Estimated cost per ml Prolensa Price not available Voltaren Ophtha $3.60 Apo-Ketorolac $2.60 Ilevro $8.00 Nevanac $4.25 Insufficient information. Page 11 of 20 Q2 2015

12 Rosiver (ivermectin) Cream % Galderma Canada Inc. 84:04.12 Scabicides and Pediculicides Rosiver is indicated for the treatment of inflammatory lesions of rosacea in adults 18 years of age and older. Apply to affected areas of the face once daily. MetroGel / MetroCream / Noritate cream (metronidazole); Finacea Gel (azelaic acid); Onreltea (brimonidine). The mechanism of action of Rosiver cream in treating rosacea lesions is unknown; however, ivermectin has both anti-inflammatory and antiparasitic properties that have been utilized orally in the treatment of rosacea-like demodicidosis with topical promethazine and as monotherapy topically for head lice and orally for chronic blepharitis secondary to Demodex folliculorum. It is thought that the commensal saprophytic mite, D. foliculorum, colonizes piloseabcous follicles of the skin leading to an inflammatory response resulting in lesions of rosacea. Selective binding of ivermectin to glutamate-gated chloride channels in invertebrates has been shown to reduce Demodex colonization in both demodicidosis and blepharitis. Ivermectin induces anti-inflammatory effects via nuclear factor-κb pathway inhibition and subsequently decreases the release of inflammatory cytokines. In randomized controlled trials, ivermectin 1% cream was shown to be safe and effective for papulopustular rosacea compared to placebo vehicle. It was also shown to be superior compared to metronidazole 0.75% cream in Investigators Global Assessment of lesions with fewer local side effects and high levels of patient satisfaction. It was also shown to be associated with fewer side effects compared to azelaic acid. Rosiver cream provides a new alternative for the treatment of patients with rosacea, a chronic and progressive cutaneous disorder with no available curative treatment. Comparative Pricing Drug Estimated cost per gram Rosiver $2.70 MetroGel $0.70-$1.50 MetroCream $0.70 Noritate $0.60 Finacea $0.65 Minimal impact. Manage with Step Therapy Program to optimize cost-effective use of drugs. Page 12 of 20 Q2 2015

13 Sivextro (tedizolid phosphate) Tablet; Intravenous injection mg tablet mg/vial Cubist Pharmaceuticals Canada Inc. 08:12.28 Misc. Antibacterials *Canadian Product Monograph not available; information from US Food and Drug Administration (FDA) Prescribing information and Health Canada SBD for Sivextro* Sivextro is an antibacterial agent indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus aureus (including methicillinresistant [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus Group (including Streptococcus anginosus, Streptococcus intermedius, and Streptococcus constellatus). The recommended dosage of Sivextro is 200 mg administered once daily for six (6) days either orally (with or without food) or as an intravenous (IV) infusion in patients 18 years of age or older. Zyvoxam (linezolid) A number of antimicrobial agents are available for the treatment of ABSSSI, an indication that includes clinical syndromes such as cellulitis, major abscesses, and wound infections. The majority of ABSSSI infections are caused by Gram-positive pathogens such as S. aureus (including MRSA) and S. pyogenes. The benefit of systemic antimicrobial therapy is clearly established in cellulitis and wound infections and clinicians agree that more severe or larger abscesses in specific locations, in debilitated populations, or when surrounded by a significant area of redness/cellulitis also require systemic antimicrobial therapy in addition to surgical drainage. The availability of a new, well-tolerated and effective antibiotic option that allows for transition from once daily IV-to-PO therapy at the same dose for the treatment of ABSSSI across different patient types (eg, elderly, renal- and hepatic-impaired patients) is an important clinical advantage. Resistance to existing antibiotics for the treatment of ABSSSI is emerging as a serious clinical problem; tedizolid has a different molecular target than many other available agents for these pathogens and thus retains antimicrobial activity against organisms such as MRSA. Sivextro (tedizolid phosphate), similar to linezolid, it appears to have activity against a range of Gram positive pathogens. Tedizolid has demonstrated potent in vitro activity against multidrug-resistant gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, including some linezolid-resistant strains. Tedizolid has a favourable pharmacokinetic profile that allows for once-daily dosing and easy i.v.-to-oral conversion. Unlike linezolid, tedizolid has not been shown to interact with serotonergic agents in clinical studies. No dosage adjustment is required for tedizolid phosphate when treating patients with renal impairment, including those on hemodialysis, or for patients with severe hepatic impairment. Sivextro provides an alternative to linezolid with potential safety advantages in terms of reduced MAO interactions, hematologic toxicity and neurotoxicity. It is generally well tolerated with an easy IV to oral switch option and a 6-day treatment course for the treatment of ABSSSI. Page 13 of 20 Q2 2015

14 Comparative Pricing Drug Estimated treatment cost Sivextro Price not available Sandoz-Linezolid tablet $775-$2,200 Insufficient information. Oral tablet for outpatient use while injection for hospital use. Page 14 of 20 Q2 2015

15 Zydelig (idelalisib) Tablet mg mg Gilead Sciences Canada Inc. 10:00.00 Antineoplastic Agents Chronic Lymphocytic Leukemia (CLL) Zydelig (idelalisib) is indicated in combination with rituximab for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL). [Approval without conditions] Follicular Lymphoma (FL) Zydelig (idelalisib) is indicated as a monotherapy for the treatment of patients with follicular lymphoma who have received at least two prior systemic regimens and are refractory to both rituximab and an alkylating agent. [Conditional marketing approval, NOC/c] Treatment is continued until disease progression or intolerance occurs. CLL The recommended dose of Zydelig is 150 mg administered orally twice daily in combination with rituximab (8 cycles of rituximab, first cycle at 375 mg/m 2, subsequent cycles at 500 mg/m 2 ). FL The recommended dose of Zydelig is 150 mg administered orally twice daily. CLL 1st Line good performance status (PS): fludarabine + cyclophosphamide + rituximab (FCR) chemotherapy; poor PS: [chlorambucil or bendamustine] +/- rituximab; 2nd line +: Arzerra (ofatumumab, single agent); Imbruvica (ibrutinib, single agent) FL most treatment alternatives consist of rituximab combined with an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, fludarabine); lenalidomide + dexamethasone (off-label use of lenalidomide). Zydelig (idelalisib) is a cancer medicine that is used to treat two types of blood cancer: chronic lymphocytic leukaemia (a cancer of a type of white blood cells called B lymphocytes) and follicular lymphoma (one of another group of cancers that affect B lymphocytes). In chronic lymphocytic leukaemia, Zydelig is used in combination with another medicine (rituximab) in patients who have received at least one previous treatment and in patients who have genetic mutations in their cancer cells called 17p deletion or TP53 mutation that make them unsuitable for treatment with a combination of chemotherapy medicines and immunotherapy (treatments that stimulate the immune system to kill cancer cells). In follicular lymphoma, Zydelig is used in patients whose disease has not responded to two previous treatments. Zydelig blocks the effects of an enzyme called PI3K-delta. This enzyme plays a role in the growth, migration and survival of white blood cells but is overactive in blood cancers, where it enables the survival of the cancer cells. By targeting this enzyme and blocking its effects, Zydelig causes death of the cancer cells, thereby delaying or stopping the progression of the cancer. Zydelig provides a chemotherapy-free option for the treatment of patients with relapsed CLL. Idelalisib plus rituximab demonstrated a significant improvement in Overall Survival, Progression-Free Survival, Overall Response Rate and Quality of Life compared to treatment with placebo plus rituximab while being generally well tolerated in relapsed CLL patients with poor prognostic factors. Zydelig provides another therapeutic option for individuals with FL who have failed two or more therapies including those with rituximab and alkylating agents, and thus have few other alternatives available to them. Page 15 of 20 Q2 2015

16 Comparative Pricing Drug Estimated monthly cost Zydelig $5,500 Imbruvica $8,700 Arzerra $79,000 (full treatment course) Intermediate impact partial cost shift. Manage similar to other oral cancer therapies. Page 16 of 20 Q2 2015

17 Zykadia (ceritinib) Capsule mg Novartis Pharmaceuticals Canada Inc. 10:00.00 Antineoplastic Agents Zykadia (ceritinib) indicated as monotherapy for use in patients with anaplastic lymphoma kinase (ALK)-positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) who have progressed on or who were intolerant to crizotinib. 750 mg taken orally once daily. Treatment should be continued as long as the patient is deriving clinical benefit from therapy. Xalkori (crizotinib); Chemotherapy: cisplatin/carboplatin + gemcitabine/ pemetrexed. Ceritinib is a kinase inhibitor and is most active in inhibiting anaplastic lymphoma kinase (ALK) and the proliferation of ALK-dependent cancer cells. Anaplastic lymphoma kinase [ALK]) is a new predictive biomarker that has been identified in a small subset of patients with NSCLC. It is estimated that 2-7% of patients have ALK gene mutations. These patients tend to be younger, male, non-smokers or light smokers. Efficacy was established in a single-arm study (n=163), where ceritinib produced an overall response rate of 43.6% in patients who progressed on or were intolerant to crizotinib (91%) or at least 2 prior therapies (84%). Complete responses occurred in 2.5% of patients and partial responses in 41.1%, with a median duration of response of 7.1 months. Zykadia provides a treatment alternative for those who either no longer respond to or are intolerant to crizotinib (Zalkori). Comparative Pricing Drug Estimated monthly cost Zykadia $11,000 Xalkori $9,500 Intermediate impact. Manage with Prior Authorization to ensure appropriate utilization. Page 17 of 20 Q2 2015

18 FIRST TIME GENERICS First Time Generic Drugs (Notices of Compliance (NOCs) from February 24, 2015 to May 20, 2015) Generic Name Reference Drug (Brand) Rank by ingredient cost in 2014 Manufacturer Route of Administration Approved Indications/ Comments Diclofenac sodium ophthalmic solution Ciclesonide nasal spray Voltaren Ophtha 723 Apotex Inc. Ophthalmic Omnaris 214 Apotex Inc. Intranasal Postoperative inflammation after cataract surgery. Non-chronic post-traumatic eye inflammation in non-penetrating wounds Seasonal allergic rhinitis and perennial allergic rhinitis. Varenicline Champix 158 GenMed, a division of Pfizer Canada Inc. Oral Smoking cessation treatment. Clindamycin / benzoyl peroxide gel Clindoxyl 126 Taro Pharmaceuticals Inc. Topical Acne Page 18 of 20 Q2 2015

19 PRODUCT LINE-EXTENSIONS Product Line Extensions (Notices of Compliance (NOCs) from February 24, 2015 to May 20, 2015) Band name Chemical name Manufacturer Dosage form Saxenda Liraglutide Novo Nordisk Canada Inc. Jinarc Tolvaptan Otsuka Pharmaceutical Company Ltd. Synagis Palivizumab AbbVie Corp. Velcade Bortezomib Janssen Inc. Subcutaneous injection Tablet Solution for intramuscular injection Intravenous / Subcutaneous injection Type of Line Extension New brand, new indication New brand, new indication New dosage form New indication Tafinlar Dabrafenib GlaxoSmithKline Inc. Capsule New indication Kalydeco Ivacaftor Vertex Pharmaceuticals (Canada) Inc. Egrifta Tesamorelin Theratechnologies Inc. Asmanex Twisthaler Mometasone furoate Merck Canada Inc. Tablet Subcutaneous injection Dry powder inhaler New indication New strength New strength; new indication Specifics/ Comments New dose of liraglutide indicated for adjunctive use in chronic weight management. Currently available brand, Victoza, is indicated for adjunctive use in controlling blood glucose in patients with type 2 diabetes. New split dose regimen of tolvaptan indicated to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). Currently available brand, Samsca, is indicated for treatment of non-hypovolemic hyponatremia. New dosage form is solution for injection which eliminates the need to reconstitute the product from lyophilized powder. New indication for previously untreated mantle cell lymphoma (MCL). Previously indicated for patients with MCL who have relapsed or were refractory to prior therapy, as well as patients with various stages of multiple myeloma. Tafinlar is now approved for use in combination with the MEK inhibitor, Mekinist (trametinib) for patients with advanced melanoma and a BRAF V600 mutation. Use expanded to include patients 18 years and older with an R117H mutation on the CFTR gene. 1mg/vial strength made available as a solution to production problems with the 2mg/vial strength previously approved. New 100mcg strength approved to facilitated expanded indication for use in patients 4 years of age and older (previously only approved for use in patients 12 years of age and older). Page 19 of 20 Q2 2015

20 PRODUCT LINE-EXTENSIONS (continued) Product Line Extensions (Notices of Compliance (NOCs) from February 24, 2015 to May 20, 2015) Band name Chemical name Manufacturer Dosage form Ibavyr Humalog KwikPen U-200 Vyvanse Ribavirin Insulin lispro Lisdexamfetamine dimesylate Pendopharm division of Pharmascience Inc. Eli Lilly Canada Inc. Ozurdex Dexamethasone Allergan Inc. Omnitrope Somatropin Sandoz Canada Inc. Tablet Subcutaneous injection Type of Line Extension New strength New strength Shire Pharma Canada ULC Capsule New strength Intravitreal implant Subcutaneous injection New indication New indication Xtandi Enzalutamide Astella Pharma Canada Inc. Capsule New indication Revolade Eltrombopag olamine Toujeo Insulin glargine Sanofi-Aventis Canada Inc. Specifics/ Comments New strength of 200mg is added to currently available 400mg and 600mg strengths. New strength of 200U/ml for use in patients requiring daily doses > 20 units of rapid-acting insulin. 10mg strength added to currently available 20mg, 30mg, 40mg, 50mg, and 60mg strengths. Diabetic macular edema (DME) in adult patients who are pseudophakic. New pediatric indications: Small for Gestional Age, Turner Syndrome, Idiopathic Short Stature. Adult indications revised to align with Genotropin. Indicated for treatment of metastatic castration resistant prostate cancer in the early disease setting (i.e., use of prior chemotherapy no longer required). GlaxoSmithKline Inc. Tablet New indication Severe aplastic anemia. Subcutaneous injection New brand; new strength Revlimid Lenalidomide Celgene Inc. Capsule New strength New brand of Lantus (insulin glargine U-100) with a higher strength of 300 units per ml. 20mg strength added to currently available 5mg, 10mg, 15mg, and 25mg strengths. Authors: Aaron Aoki, RPh, BScPhm, MBA, CDE, CRE; Moe Abdallah, B.Sc., B.Sc.Phm; Paul Thompson, B.Sc.Phm, RPh; Priscilla Po, PharmD, RPh Page 20 of 20 Q2 2015