New Drug Update 2015 – 2016 Rachael McCaleb, PharmD

New Drug Update 2015 – 2016 Rachael McCaleb, PharmD
Assistant Professor, Department of Pharmacy Practice University of Arkansas for Medical Sciences College of Pharmacy Clinical Consultant United States Food and Drug Administration National Center for Toxicological Research

Disclosures I have nothing to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation.

Objectives Identify the indications and routes of administration of the new therapeutic agents. Review the mechanism of action and dosing parameters for each new therapeutic agent. Compare the new therapeutic agents to the older therapeutic agents to which they are most similar in activity. Identify information regarding the new therapeutic agents that should be communicated to patients.

Overview Novel Drug Approvals (July 2015 – July 2016) New Dosage Forms

Drug Approvals Number of applications submitted has remained relatively the same. 45 novel new drugs and biologics approved Highest number since 1996 (53 new drugs products) Previous 10-year average (2006 – 2014) of 28 novel new drugs approvals per year *Up to August 1 Jenkins J. U.S. Food and Drug Administration. Novel New Drugs Summary June 23,

2015 Drug Approvals: Impact of Public Health
31% Fast Track 47% Rare or Orphan Diseases 22% Breakthrough Therapies 36% First-in-Class Breakthrough therapies: drugs with preliminary clinical evidence demonstrating substantial improvement in results Fast-track: drugs with the potential to address unmet medical needs Jenkins J. U.S. Food and Drug Administration. Novel New Drugs Summary June 23,

Drug Categories Cardiology Dermatology Women’s Health Endocrinology
Nephrology Psychology Pulmonary Neurology Hepatology Infectious Disease Oncology Other

Cardiology Idarucizumab (Praxbind®)

Idarucizumab (Praxbind®)
Indication: Reversal of dabigatran for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding Approval Date: October 10, 2015 MOA: Humanized monoclonal antibody binds to dabigatran and its metabolites Affinity ~350 times greater than thrombin Neutralizes anticoagulant effect within minutes Praxbind (idarucizumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.

Pharmacodynamics/Kinetics: Onset: effect within minutes and hemostasis restored at median of 11.4 hours Dose: IV - 5 gm – administered as 2 separate 2.5 gm doses no more than 15 minutes apart May consider administration of an additional 5 gm if necessary (limited data to support) Praxbind (idarucizumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.

Warnings: Thromboembolic risk – resume anticoagulant therapy as soon as appropriate Dabigatran can be re-initiated 24 hours after idarucizumab administration Hypersensitivity reactions Re-elevation of coagulation parameters – consider an additional full dose (5 gm) Elevated coagulation parameters with clinically relevant bleed or second emergency surgery needed Hereditary fructose intolerance – contains 4 gm sorbitol Adverse Effects: Headache, hypokalemia, delirium, constipation, pyrexia, and potential for immunogenicity In treated patients, treatment-emergent antibodies with low titers were observed (9/224). Praxbind (idarucizumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015. Pollack CV Jr, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015;373(6):

Evidence: Reduction in dabigatran plasma concentration was observed immediately after administration of idarucizumab 5 gm and coagulation parameters returned to baseline Studies in healthy volunteers (n=283) Phase 3 single cohort case series trial in patients ≥18 years currently taking dabigatran Group A: Life-threatening or uncontrolled bleeding (n=66) Group B: Emergency surgery required (n=57) Results: Reversal effects evident immediately after administration of 5 gm Median maximum reversal in first 4 hours was 100% RE-VERSE AD (Interim analysis) (n=123) In treated patients, treatment-emergent antibodies with low titers were observed (9/224). **NEED MORE INFO ON RE-VERSE AD** Praxbind (idarucizumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.

Dermatology Ixekizumab (Taltz®)

Ixekizumab (Taltz®) Indication: Treatment of adults with moderate-to-severe plaque psoriasis Approval Date: March 22, 2016 MOA: Humanized monoclonal antibody against interleukin 17 Inhibits proinflammatory cytokines and chemokines Secukinumab (Cosentyx®) Dose: 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks Taltz (ixekizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Co; March 2016.

Ixekizumab (Taltz®) Adverse Effects: Injection site reactions, upper respiratory tract infections, nausea, and tinea infections Monitoring: Improvement in signs and symptoms is indicative of efficacy Tuberculosis infection before, during, and after treatment Onset or exacerbation of inflammatory bowel disease Interactions: Immunosuppressants - avoid combination Infections occurred in 27% of subjects treated with TALTZ (1.2 per subject-year of follow-up) compared to 23% of subjects treated with placebo Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group (Crohn’s disease 0.1%, ulcerative colitis 0.2%) than the placebo group (0%) during the 12-week, placebo-controlled period Taltz (ixekizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Co; March 2016.

sPGA of “0” (clear) or “1” (minimal)
Ixekizumab (Taltz®) Evidence: UNCOVER 1, 2, and 3 trials UNCOVER 2 & 3 included active comparator with etanercept 50 mg twice weekly Ixekizumab (80 mg Q4W and 80 mg Q2W doses) were superior to etanercept on sPGA and PASI scores UNCOVER 1 UNCOVER 2 UNCOVER 3 TALTZ 80 mg Q2W (N=433) % Placebo (N=431) Q2W (N=351) Placebo (N=168) Q2W (N=385) Placebo (N=193) sPGA of “0” (clear) or “1” (minimal) 82 3 83 2 81 7 PASI 75 89 4 90 87 PASI 90 71 1 68 PASI 100 35 40 38 UNCOVER: Primary endpoints :PASI 75, the proportion of subjects who achieved at least a 75% reduction in the PASI composite score, and 2) sPGA of “0” (clear) or “1” (minimal), the proportion of subjects with an sPGA 0 or 1 and at least a 2-point improvement. Active comparator group: was superior to entracept 50mg twice weekly Some evidence available in RA (Phase 2) but not FDA approved for RA **ADD INFO** sPGA = static Physician Global Assessment; PASI = Psoriasis Area and Severity Index Taltz (ixekizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Co; March 2016.

Ixekizumab (Taltz®) Place in Therapy: Current guidelines do not include IL-17 inhibitors Price (AWP): Prefilled syringe - 80 mg/mL (1 mL) - $ Taltz (ixekizumab) [prescribing information]. Indianapolis, IN: Eli Lilly and Co; March 2016.

Women’s Health Flibanserin (Addyi®)

Flibanserin (Addyi®) Indication: Lack or loss of sexual desire in premenopausal women Approval Date: August 18, 2015 MOA: Serotonin (5-HT) receptor 1A agonist and 5-HT2A antagonist with unknown mechanism in the treatment of hypoactive sexual desire disorder (HSDD) Dose: 100 mg PO once daily at bedtime Discontinue treatment after 8 weeks if no improvement Addyi (flibanserin) [prescribing information]. Raleigh, NC: Sprout Pharmaceuticals, Inc; 2015.

Flibanserin (Addyi®) Black Box Warning: Contraindicated with alcohol, moderate-strong CYP3A4 inhibitors, or hepatic impairment due to increased risk of severe hypotension and syncope (only available though ADDYI REMS program) Adverse Effects: Dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth Evidence: Approval based on BEGONIA trial, which resulted in significant improvements in the number of satisfying sexual events and sexual desire versus placebo Addyi (flibanserin) [prescribing information]. Raleigh, NC: Sprout Pharmaceuticals, Inc; 2015.

Flibanserin (Addyi®) Place in Therapy: First FDA-approved treatment option for HSDD in premenopausal women Suboptimal benefit vs. risk trade-off Systematic review published in JAMA Internal Medicine: “Treatment with flibanserin, on average, resulted in one-half additional satisfying sexual event per month while statistically and clinically significantly increasing risk of dizziness, somnolence, nausea, and fatigue.” Price (AWP): 100mg tablet (30) – $960.00 Jaspers L, et al. Efficacy and safety of flibanserin for the treatment of hypoactive sexual desire disorder in women: a systematic review and meta-analysis. JAMA Intern Med. 2016;176(4):

Endocrinology Insulin Degludec (Tresiba®)
Insulin Aspart/Insulin Degludec (Ryzodeg® 70/30) Lixisenatide (Adlyxin®)

Insulin Degludec (Tresiba®)
Indication: Glycemic control in adults with diabetes mellitus (type 1 and type 2) Approval Date: September 25, 2015 MOA: Ultra long-acting basal insulin that lowers blood glucose by stimulating peripheral glucose uptake and by inhibiting hepatic glucose production Dose: Patient-dependent; insulin-experienced patients: same unit dose Supplied in 100 units/mL or 200 units/mL Flex Pens Tresiba (insulin degludec) [prescribing information]. Plainsboro, NJ: Novo Nordisk; 2015.

Adverse Effects: Hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, weight gain Evidence: Approval based on BEGIN trial that showed non-inferiority to comparator products DEVOTE trial comparing cardiovascular safety to that of insulin glargine in patients with type 2 DM ongoing Longer duration of 42 hours Does not appear to lead to “dose stacking” or accumulation “Once daily at any time of the day” – ↓ adherence? Add info on evidence Tresiba (insulin degludec) [prescribing information]. Plainsboro, NJ: Novo Nordisk; 2015.

Price (AWP): 100 units/mL (3 mL) - $106.52 200 units/mL (3mL) - $213.05 Comparators: Generic Brand Packaging Price (AWP) Insulin glargine Lantus SoloStar® 100 units/mL (3 mL) $89.46 Toujeo SoloStar® 300 units/mL (3 mL) $134.19 Insulin detemir Levemir FlexTouch® $96.84 Insulin NPH Humulin N KwikPen® $104.94 Tresiba (insulin degludec) [prescribing information]. Plainsboro, NJ: Novo Nordisk; 2015.

Insulin Aspart/Insulin Degludec (Ryzodeg® 70/30)
Indication: Glycemic control in adults with diabetes mellitus (type 1 and type 2) Approval Date: September 25, 2015 MOA: Fixed dose of an ultra long-acting basal insulin combined with rapid-acting insulin analog that lowers blood glucose Dose: Patient-dependent dosing administered SubQ once or twice daily with any meal Ryzodeg (insulin degludec and insulin aspart) [prescribing information]. Plainsboro, NJ: Novo Nordisk; September 2015.

Lixisenatide (Adlyxin®)
Indication: Glycemic control in adults with type 2 diabetes mellitus Approval Date: July 27, 2016 MOA: Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Dose: Subcutaneous Initial: 10 mcg once daily for 14 days Day 15, increase to 20 mcg once daily Administered within 1 hour before first meal of the day Need to include more if available Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2016.

Adverse Effects: Nausea, vomiting, headache, diarrhea, dizziness, and hypoglycemia Interactions: Orally administered medications – lixisenatide delays gastric emptying Oral contraceptives – may decrease effectiveness --- take 1 hour prior to or 11 hours following administration of lixisenatide Need to include more if available Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2016.

Evidence: Monotherapy (n=241) Lixisenatide 20 mcg resulted in significant reductions in HbA1C at week 12 from baseline compared to placebo Combination Therapy w/Metformin (n=323) Lixisenatide 20 mcg resulted in significant reductions in HbA1C and fasting plasma glucose at week 24 from baseline compared to placebo Combination Therapy w/Sulfonylurea (±Metformin) (n=859) Lixisenatide 20 mcg resulted in significant reductions in HbA1C at week 24 from baseline compared to placebo Combination Therapy w/Pioglitazone (±Metformin) (n=484) Combination Therapy w/Basal Insulin (±OAD) (n=496) Need to include more if available Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2016.

Supplied: 50 mcg/mL (3 mL) – 14 pre-set doses; 10 mcg/dose (green pen) 100 mcg/mL (3 mL) - 14 pre-set doses; 20 mcg/dose (burgundy pen) Price (AWP): Not available Comparators: Need to include more if available Drug Dosing (SubQ) Packaging Price (AWP) Albiglutide (Tanzeum®) Once weekly 30 mg pen 50 mg pens $131.81 Dulaglutide (Tanzeum®) 0.75 mg/0.5 mL pen 1.5 mg/0.5 mL pens $172.44 Exenatide (Byetta®) Twice daily 5 mcg/0.02 mL (2.4 mL) pen 10 mcg/0.04 mL (2.4 mL) pen $729.04 Exenatide (Bydureon®) 2 mg pen $173.00 Liraglutide (Victoza®) Once daily 18 mg/3 mL (3 mL) $277.02 Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; July 2016.

Nephrology Patiromer (Veltassa®)

Patiromer (Veltassa®)
Indication: Hyperkalemia Approval Date: October 21, 2015 MOA: Increases fecal potassium excretion through binding of potassium in lumen of GI tract Dose: Initial 8.4 grams once daily Titrate: 8.4 grams at 1-week intervals to goal serum potassium level Maximum daily dose = 25.2 grams Oral powder for suspension; 8.4, 16.8, and 25.2 gram packets Info: how mechanism differs from other available agents Veltassa (patiromer) [prescribing information]. Redwood City, CA: Relypsa, Inc.; 2015.

Black Box Warning: Binds to many orally administered medications, which could decrease their absorption and reduce their effectiveness Administer at least 6 hours before or 6 hours after Veltassa Adverse Effects: Constipation, hypomagnesaemia, diarrhea, nausea, abdominal discomfort, flatulence Evidence: Approval based on AMETHYST-DN trial which resulted in statistically significant decreases in serum potassium after 4 weeks of treatment, lasting through week 52 Veltassa (patiromer) [prescribing information]. Redwood City, CA: Relypsa, Inc.; 2015.

Place in Therapy: Second-line treatment for hyperkalemia Recommend other strategies before using Decrease doses of meds that increase potassium Thiazide or loop diuretic Limit dietary potassium, including salt substitutes Should not be used as an emergency treatment of hyperkalemia due to delayed onset of action Does not increase sodium (may be preferred over sodium polystyrene sulfonate (i.e. Kayexalate); but cost more $$$ Veltassa (patiromer) [prescribing information]. Redwood City, CA: Relypsa, Inc.; 2015.

Price (AWP): Patiromer Kayexalate Oral suspension – 15 gm/60 mL (60 mL) - $11.25 Rectal suspension – 30 gm/120 mL (120mL) - $44.10 Strength Number of packs Price 8.4 gm 4 $142.80 16.8 gm 1 $23.80 25.2 gm Veltassa (patiromer) [prescribing information]. Redwood City, CA: Relypsa, Inc.; 2015.

Psychology Aripiprazole lauroxil (Aristada®) Cariprazine (Vraylar®)
Pimavanserin tartrate (Nuplazid®)

Aripiprazole lauroxil (Aristada®)
Indication: Atypical antipsychotic indicated for the treatment of schizophrenia Approval Date: October 6, 2015 MOA: Prodrug of aripiprazole Aripiprazole - partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5- HT2A receptors Dose: Establish tolerability with oral aripiprazole Oral aripiprazole 10 mg/day → IM aripiprazole lauroxil 441 mg per month Oral aripiprazole 15 mg/day → IM aripiprazole lauroxil 662 mg per month Oral aripiprazole ≥20 mg/day → IM aripiprazole lauroxil 882 mg every 4 or 6 weeks Continue oral aripiprazole for 21 days following initial IM dose of aripiprazole lauroxil Artistada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; May 2016.

Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis Adverse Effects: Extrapyramidal symptoms, hyperglycemia, dyslipidemia, impulse control disorder, orthostatic hypotension, and weight gain Interactions: CYP3A4 (strong) – reduce 882 mg dose to 441 mg; no dosage adjustment necessary for 441 mg dose CYP2D6 (strong) – reduce 882 mg dose to 441 mg; no dosage adjustment necessary for 441 mg dose CYP3A4 & CYP2D6 (strong) – do not use 882 and 662 mg doses; no dosage adjustment necessary for 441 mg dose Artistada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; May 2016.

Evidence: 12-week, multicenter, double-blinded, randomized control trial 632 patients randomized to receive once-monthly IM aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or placebo Results: Significant reduction in Positive and Negative Syndrome Scale with both aripiprazole lauroxil groups compared to placebo at day 85 (Primary endpoint) Change from baseline: Placebo: -9.8 Aripiprazole lauroxil 441 mg: -20.9 Aripiprazole lauroxil 882 mg: -21.8 Significant improvements in Clinical Global Impression Improvement Scale with both aripiprazole lauroxil groups compared to placebo at day 85 Artistada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; May 2016.

Price (AWP): Comparator: Aripiprazole Strength Price 441 mg/1.6 mL (1.6 mL) $ 662 mg/2.4 mL (2.4 mL) $ 882 mg/3.2 mL (3.2 mL) $ Strength Price Abilify® (oral) 2, 5, 10, 15 mg tablet (30) $ 20, 30 mg tablet (30) $ Generic (oral) $963.27 $ Abilify Maintena® (IM) 300 mg $ 400 mg $ Artistada (aripiprazole lauroxil) [prescribing information]. Waltham, MA: Alkermes Inc; May 2016.

Cariprazine (Vraylar®)
Indication: Atypical antipsychotic indicated for the treatment of schizophrenia Acute treatment of manic or mixed episodes associated with bipolar I disorder Approval Date: September 17, 2015 MOA: Partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A receptors Dose: Schizophrenia – Initial: 1.5 mg once daily; Maximum dose: 6 mg daily Bipolar I Disorder – Initial: 1.5 mg once daily; Maximum dose: 6 mg daily Vraylar (cariprazine) [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2015.

Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis Adverse Effects: Extrapyramidal symptoms, hyperglycemia, dyslipidemia, impulse control disorder, orthostatic hypotension, and weight gain Interactions: CYP450 Inducers – use not recommended CYP450 Inhibitor (strong) – reduce cariprazine by 50% Vraylar (cariprazine) [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2015.

Evidence: Schizophrenia Three, 6-week, placebo-controlled, double-blinded, randomized control trial Cariprazine demonstrated significant improvement in mean reduction in Positive and Negative Syndrome Scale at week 6 compared to placebo Improvement versus placebo: Cariprazine 1.5 mg: 64% Cariprazine 3 mg: 41 – 75% Cariprazine 4.5 mg: 89% Cariprazine 6 mg: 61% Dose-related increases in certain adverse reactions (gastrointestinal, nervous system, and vascular disorders) was observed at dose above 6 mg (maximum recommended dose is 6 mg/day) Vraylar (cariprazine) [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2015.

Evidence: Bipolar I Disorder Three, 3-week, placebo-controlled, double-blinded, randomized control trial Cariprazine demonstrated significant improvement in mean reduction in Young Mania Rating Scale at week 3 compared to placebo Improvement versus placebo: Cariprazine 3-6 mg: 49% Cariprazine 6-12 mg: 48% Dose-related increases in certain adverse reactions (gastrointestinal, nervous system, and vascular disorders) was observed at dose above 6 mg (maximum recommended dose is 6 mg/day) Vraylar (cariprazine) [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2015.

Price (AWP): 1.5, 3, 4.5, 6 mg capsule (30) - $ Vraylar (cariprazine) [prescribing information]. Parsippany, NJ: Actavis Pharma; September 2015.

Pimavanserin tartrate (Nuplazid®)
Indication: Treatment of hallucinations and delusions associated with Parkinson disease psychosis Approval Date: April 29, 2016 MOA: Inverse agonist/antagonist at the 5-HT2A and 5-HT2C receptors Dose: 34 mg once daily Nuplazid (pimavanserin) [prescribing information]. San Diego, CA: Acadia Pharmaceuticals Inc: April 2016.

Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis Adverse Effects: CNS depression, orthostatic hypotension, peripheral edema, and QTc prolongation Interactions: CYP450 Inducers – monitor; dosage increase may be necessary CYP450 Inhibitor (strong) – 17 mg once daily Nuplazid (pimavanserin) [prescribing information]. San Diego, CA: Acadia Pharmaceuticals Inc: April 2016.

Evidence: 6-week, randomized, double-blind, placebo-controlled study (n=199) Pimavansrin 34 mg versus placebo once daily Results: Pimavansrin was superior to placebo in decreasing the frequency and/or severity of hallucinations and delusions in patients with Parkinson disease psychosis at week 6 PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD) P=0.0006 Nuplazid (pimavanserin) [prescribing information]. San Diego, CA: Acadia Pharmaceuticals Inc: April 2016.

Place in Therapy: First-in-class for treatment of hallucinations and delusions associated with Parkinson’s disease psychosis Price (AWP): 17 mg (60) – $ PD-adapted Scale for the Assessment of Positive Symptoms (SAPS-PD) Nuplazid (pimavanserin) [prescribing information]. San Diego, CA: Acadia Pharmaceuticals Inc: April 2016.

Pulmonary Mepolizumab (Nucala®) Reslizumab (Cinqair®)
Selexipag (Uptravi®) Lumacaftor and Ivacaftor (Orkambi®)

Mepolizumab (Nucala®)
Indication: Add-on maintenance treatment of severe asthma in adults and children (≥12 years) with an eosinophilic phenotype Approval Date: November 4, 2015 MOA: Interleukin-5 antagonist (IL-5); reduces production/survival of eosinophils by inhibiting IL-5 signaling Dose: 100 mg subcutaneously once every 4 weeks Nucala (mepolizumab) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2015.

Adverse Effects: Hypersensitivity, headache, immunogenicity, infections (herpes zoster, influenza, and parasitic) Interactions: No known significant interactions Nucala (mepolizumab) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2015.

Evidence: Three, double-blind, randomized, placebo-controlled trials (Trial 1 – 3) Exacerbation (Trial 1 & 2) Mepolizumab 100 mg SubQ resulted in significant reductions in exacerbations (all exacerbations, exacerbations requiring systemic corticosteroid use, and exacerbations resulting in hospitalizations and/or emergency room visits) compared to placebo Oral corticosteroid reduction (Trial 3) Mepolizumab SubQ resulted in significant reductions in daily maintenance oral corticosteroid dose compared to placebo Patients achieving at ≥ 50% reduction 54% - mepolizumab 33% - placebo Nucala (mepolizumab) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2015.

Place in Therapy: May be considered at Step 5 Based on the Global Strategy for Asthma Management and Prevention Guidelines Price (AWP): 100 mg - $ Nucala (mepolizumab) [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; November 2015. Asthma, Global Initiativefor. "Global strategy for asthma management and prevention." (2016). Accessed Aug 31, 2016.

Reslizumab (Cinqair®)
Indication: Add-on maintenance treatment of severe asthma in adults with an eosinophilic phenotype Approval Date: March 23, 2016 MOA: Interleukin-5 antagonist (IL-5); reduces production/survival of eosinophils by inhibiting IL-5 signaling Dose: 3 mg/kg IV once every 4 weeks Cinqair (reslizumab) [prescribing information]. Frazer, PA: Teva; March 2016.

Black Box Warning: Anaphylaxis Occurred in 0.3% of patients in placebo-controlled studies Adverse Effects: Anaphylaxis, malignancies, increases in creatine phosphokinase (transient), and antibody development Interactions: No known significant interactions In placebo-controlled clinical studies, 6/1028 (0.6%) patients receiving 3 mg/kg CINQAIR had at least 1 malignant neoplasm reported compared to 2/730 (0.3%) patients in the placebo group. The observed malignancies in CINQAIR-treated patients were diverse in nature and without clustering of any particular tissue type. The majority of malignancies were diagnosed within less than six months of exposure to CINQAIR. Cinqair (reslizumab) [prescribing information]. Frazer, PA: Teva; March 2016.

Evidence: Four, randomized, double-blind, placebo-controlled study (n=981) (Studies I- IV) Exacerbations (Studies I & II) Reslizumab 3 mg/kg every 4 weeks resulted in significant reductions in exacerbations (all exacerbations, exacerbations requiring systemic corticosteroid use, and exacerbations resulting in hospitalizations and/or emergency room visits) compared to placebo Lung function (Studies I – IV (Primary endpoint: Studies III & IV)) Reslizumab 3 mg/kg every 4 weeks resulted in greater improvements in FEV1 compared to placebo Study III also included a 0.3 mg/kg dose – resulted in numerically smaller changes in FEV1 Cinqair (reslizumab) [prescribing information]. Frazer, PA: Teva; March 2016.

Place in Therapy: Current guidelines do not include Price (AWP): 100 mg/10 mL (10 mL) – $ Cinqair (reslizumab) [prescribing information]. Frazer, PA: Teva; March 2016.

Selexipag (Uptravi®) Indication: Treatment of pulmonary arterial hypertension (PAH) Approval Date: December 21, 2015 MOA: Selective prostacyclin IP receptor agonist Dose: Initial: 200 mcg twice daily; maximum dose: 1,600 mcg twice daily Uptravi (selexipag) [prescribing information]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; December 2015.

Selexipag (Uptravi®) Adverse Effects: Headache, pulmonary edema, diarrhea, nausea/vomiting, myalgia, arthralgia, and decreased hemoglobin Precautions: Avoid use in patients with severe hepatic impairment Interactions: CYP2C8 inhibitors (strong) - avoid concurrent use - ↑ in serum concentration of selexipag CYP2C8 inhibitors (moderate) - monitor therapy Uptravi (selexipag) [prescribing information]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; December 2015.

Selexipag (Uptravi®) Evidence:
GRIPHON (Multi-center, double-blind, placebo-controlled, parallel group, event-driven study) (n=1156) Randomized to receive placebo or selexipag 200 mcg twice daily titrated up to 1600 mcg twice daily Primary endpoint - Time to first occurrence up to end-of-treatment of: a) hospitalization for PAH, b) disease progression, c) death, d) initiation of parenteral prostanoid therapy or chronic oxygen therapy, and e) need for lung transplantation Results: Selexipag resulted in a 40% reduction (p <0.0001) in occurrence of primary endpoint events compared to placebo Largest benefit noted for the reduction in hospitalizations for PAH Uptravi (selexipag) [prescribing information]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; December 2015.

Selexipag (Uptravi®) Price (AWP): Received orphan drug designation
200 mcg tablet (60) – $11,208.00 400, 600, 800, 1000, 1200, 1400, 1600 mcg tablet (60) – $17,424.00 Received orphan drug designation Uptravi (selexipag) [prescribing information]. South San Francisco, CA: Actelion Pharmaceuticals US Inc; December 2015.

Lumacaftor/ivacaftor (Orkambi®)
Indication: Treatment of cystic fibrosis (CF) in patients who are homozygous for the F508del mutation in the CFTR gene (≥12 yrs) Approval Date: July 2, 2015 MOA: Lumacaftor improves the conformational stability of F508del-CFTR; increasing processing and trafficking of mature protein Ivacaftor is a CFTR potentiator that facilitates increased chloride transport Dose: Lumacaftor 400 mg/ivacaftor 250 mg every 12 hours Orkambi (lumacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; May 2016.

Adverse Effects: Chest discomfort, dyspnea, nausea, increased blood pressure, increased creatine phosphokinase, and increased serum bilirubin and transaminases Interactions: CYP3A inhibitors (strong) - Initiation of lumacaftor/ivacaftor therapy when already on strong CYP3A inhibitor: Initial dose of lumacaftor 200 mg/ivacaftor 125 mg once daily increased to lumacaftor 400 mg/ivacaftor 250 mg every 12 hours in 1 week No adjustments required for patients already on lumacaftor/ivacaftor therapy who begin therapy with a strong CYP3A inhibitor Worsening of liver function (including hepatic encephalopathy) has been reported in patients with advanced liver disease Orkambi (lumacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; May 2016.

Dose Adjustments: Hepatic impairment Child-Pugh class B: lumacaftor 400 mg /ivacaftor 250 mg in the morning and lumacaftor 200 mg/ivacaftor 125 mg in the evening Child-Pugh class C: lumacaftor 200 mg/ivacaftor 125 mg every 12 hours Worsening of liver function (including hepatic encephalopathy) has been reported in patients with advanced liver disease Orkambi (lumacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; May 2016.

Evidence: Two, 24-week, randomized, double-blinded, placebo-controlled trials (TRAFFIC & TRANSPORT) (n=1108) Results: Lumacaftor/ivacaftor resulted in statistically significant improvements in percent predicted FEV1 from baseline compared to placebo at week 24 TRAFFIC: Placebo: vs lumacaftor/ivacaftor: 2.16; absolute change – 2.6% TRANSPORT: Placebo: vs lumacaftor/ivacaftor: 2.85; absolute change – 3.0% Lumacaftor/ivacaftor resulted in improvements in body mass index and cystic fibrosis questionnaire-revised score (CF respiratory symptoms) compared to placebo at week 24 Lumacaftor/ivacaftor resulted in reduced risk of pulmonary exacerbations compared to placebo at week 24 TRAFFIC: 30% reduction TRANSPORT: 40% reduction Orkambi (lumacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; May 2016.

Price: Lumacaftor 200 mg and ivacaftor 125 mg tablet (112) - $23,907.70 Ivacaftor (Kalydeco®) – Already FDA approved Price – 50, 75, 150 mg (56) - $28,675.36 Ivacaftor is considered to be ineffective in patients who are homozygous for F508del-CFTR mutation Combination lumacaftor/ivacaftor may improve clinical outcomes compared to monotherapy with each agent in these patients Orkambi (lumacaftor/ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; May 2016.

Neurology Brivaracetam (Briviact®) Daclizumab (Zinbryta®)

Brivaracetam (Briviact®)
Indication: Adjunctive therapy for partial onset seizures Approval Date: February 18, 2016 MOA: Precise mechanism is unknown. Displays high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain Dose: Initial 50 mg twice daily (oral or IV) May decrease to 25 mg twice daily or increase up to 100 mg twice daily based on tolerability Briviact (brivaracetam) [prescribing information]. Smyrna, GA: UCB; June 2016.

Adverse Effects: Fatigue, hypersomnia, drowsiness, nausea/vomiting, nystagmus, and decreased white count Interactions: Rifampin – Increase the brivaracetam dose by up to 100% Evidence: Approval based on 3 fixed-dose, randomized controlled trials which showed that patients had a statistically significant reduction in: 7-day partial-onset seizure frequency over placebo 28-day partial-onset seizure frequency over placebo Dosed at either 50mg/day or 100mg/day Studies 1 & 2 showed no benefit when added to levetiracetam Briviact (brivaracetam) [prescribing information]. Smyrna, GA: UCB; June 2016.

Place in Therapy: Add-on therapy for partial onset seizures No data available or efficacy and safety in patients younger than 16 years No added therapeutic benefit when administered in conjunction with levetiracetam Price (AWP): IV solution – 50 mg/5 mL (5 mL): $46.80 Oral tablet – 10, 25, 50, 75, 100 mg tablet (60): $ Oral solution – 10 mg/mL (300 mL): $ Rolan P, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 66 (1): 71–5.

Daclizumab (Zinbryta®)
Indication: Treatment of relapsing forms of multiple sclerosis (MS) Generally reserved for inadequate response to 2 or more MS medications Approval Date: May 27, 2016 MOA: Humanized monoclonal antibody involved in modulation of IL-2 mediated activation of lymphocytes; IL-s plays role in activating and regulating the immune system Dose: SubQ, 150 mg once monthly Zinbryta (daclizumab) [prescribing information]. Cambridge, MA: Biogen Inc; May 2016.

Black Box Warning: Hepatotoxicity including autoimmune hepatitis Other immune-mediated disorders Systemic corticosteroids for treatment of autoimmune hepatitis or immune- mediated disorders Only available through ZINBRYTA REMS Program secondary to risk of hepatic injury Adverse Events: Skin reactions, autoimmune disease, and infection Interactions: Immunosuppressants – don’t use in combination Immune-mediated disorders such as skin reactions, lymphadenopathy, and noninfectious colitis can occur in patients treated with daclizumab. REMS: Risk Evaluation and Mitigation Strategy Zinbryta (daclizumab) [prescribing information]. Cambridge, MA: Biogen Inc; May 2016.

Patients randomized to receive daclizumab 150 mg monthly or interferon-β-1a 30 mcg weekly Results: Daclizumab resulted in significantly lower annualized relapse rates compared to interferon-β-1a at week 96 Relative reduction: 45%; p<0.0001 Daclizumab resulted in significantly higher proportion of patients considered to be relapse free compared to interferon-β-1a at week 96 Study 1 (n=1941) Patients randomized to receive daclizumab 150 mg monthly or placebo Daclizumab resulted in significantly lower annualized relapse rates compared to placebo at week 52 Relative reduction: 54%; p<0.0001 Daclizumab resulted in significantly higher proportion of patients considered to be relapse free compared to placebo at week 52 Daclizumab resulted in a significantly lower proportion of new T1 Gd-enhancing and T2 hyperintense lesions compared to placebo (p<0.0001) Study 2 ( n=412) Zinbryta (daclizumab) [prescribing information]. Cambridge, MA: Biogen Inc; May 2016.

Price (AWP): 150 mg/mL (1 mL) - $ Annual Price: $98,400 Comparators: Drug Annual Price Interferon-β-1b (Betaseron®) $61,529 Glatiramer acetate (Copaxone®) $59,158 Interferon-β-1a IM (Avonex®) $62,394 Natalizumab (Tysabri®) $64,233 Interferon-β-1a SC (Rebif®) $66,394 Fingolimod (Gilenya®) $63,806 Interferon-β-1b (Extavia®) $51,427 Teriflunomide (Aubagio®) $57,553 Dimethyl fumarate (Tecfidera®) $63,315 Zinbryta (daclizumab) [prescribing information]. Cambridge, MA: Biogen Inc; May 2016.

Hepatology Daclatasvir (Daklinza®)
Elbasvir and grazoprevir (Zepatier®) Sofosbuvir and velpatasvir (Epclusa®)

Daclatasvir (Daklinza®)
Indication: Treatment of chronic hepatitis C virus (HCV) genotype 1, 3 infection in combination with other antiviral therapy Approval Date: July 24, 2015 MOA: Binds within Domain 1 of HCV nonstructural protein 5A (NS5A) and inhibits viral RNA replication and virion assembly Dose: Without cirrhosis or with compensated cirrhosis: 60 mg once daily with concomitant sofosbuvir for 12 weeks With decompensated cirrhosis or post liver transplant: 60 mg once daily with concomitant sofosbuvir and ribavirin for 12 weeks Need to add something about duration based on guidelines (PULL GUIDELINES) Daklinza (daklatasvir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; February 2016.

Adverse Effects: Fatigue, headache, nausea, anemia Interactions: Moderate/strong CPY3A4 inducers - ↓ daclatasvir concentration (may need to increase dose to 90 mg once daily) Strong CPY3A4 inhibitors - ↑ daclatasvir concentration (may need to decrease dose to 30 mg once daily) ALLY-3 SVR12 (89%; no cirrhosis – 96%; w/cirrhosis – 63%) ALLY-2 SVR12 (G1 97%; no cirrhosis – 98%; w/cirrhosis – 91%) (G3 100%) ALLY-1 SVR12 Need to add Daklinza (daklatasvir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; February 2016.

Evidence: Trial Population Study Arms and Duration ALLY-3 Genotype 3, treatment-naive and treatment- experienced, with or without cirrhosis DAKLINZA and sofosbuvir for 12 weeks ALLY-2 Genotype 1 and 3, treatment-naive and treatment- experienced, with or without cirrhosis, HCV/HIV-1 coinfection ALLY-1 Genotype 1 and 3, treatment-naive and treatment- experienced, with or without cirrhosis, including decompensated cirrhosis and post-transplant DAKLINZA and sofosbuvir and ribavirin for 12 weeks ALLY-3 SVR12 (89%; no cirrhosis – 96%; w/cirrhosis – 63%) ALLY-2 SVR12 (G1 97%; no cirrhosis – 98%; w/cirrhosis – 91%) (G3 100%) ALLY-1 SVR12 Need to add Daklinza (daklatasvir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; February 2016.

Evidence: Percentage with sustained virologic response at 12 weeks (SVR12) with DAKLINZA Trial Genotype GT-1 GT-1a GT-1b GT-3 ALLY-3 89% ALLY-2 97% 100% ALLY-1 82% 76% ALLY-3 SVR12 (89%; no cirrhosis – 96%; w/cirrhosis – 63%) ALLY-2 SVR12 (G1 97%; no cirrhosis – 98%; w/cirrhosis – 91%) (G3 100%) ALLY-1 SVR12 Need to add Daklinza (daklatasvir) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; February 2016.

Place in Therapy: Genotype 1a Genotype 1b Genotype 2 Genotype 3 Treatment-naïve Recommended Alternative Without cirrhosis Compensated cirrhosis Treatment-experienced American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. Updated July Accessed Aug

Elbasvir and grazoprevir (Zepatier®)
Indication: Treatment of chronic hepatitis C virus (HCV) genotypes 1 or 4 infection (with or without concomitant medications) Approval Date: January 28, 2016 MOA: Elbasvir binds to HCV nonstructural protein 5A (NS5A) and inhibits viral RNA replication and virion assembly Grazoprevir binds to HCV nonstructural protein 3/4 A (NS3/4A) and inhibits the proteolytic cleavage of HCV-encoded polyprotein Dose: One tablet (elbasvir 50 mg/grazoprevir 100 mg) once daily Differene Zepatier (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; January 2016.

Adverse Effects: Fatigue, headache, nausea, and increased serum bilirubin and ALT Interactions: Moderate/strong CPY3A4 inducers - ↓ elbasvir and grazoprevir concentration Co-administration with strong CPY3A4 inducers - contraindicated Strong CPY3A4 inhibitors - ↑ elbasvir and grazoprevir concentration Co-administration with strong CPY3A4 inhibitors- contraindicated Differene Zepatier (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; January 2016.

Evidence: Trial Population Study Groups and Duration C-EDGE TN (double-blind) GT 1, 4 TN with or without cirrhosis ZEPATIER for 12 weeks Placebo for 12 weeks C-SURFER GT 1 TN or TE with or without cirrhosis (Severe Renal Impairment including Hemodialysis) C-EDGE TE (open-label) GT 1, 4 TE with or without cirrhosis HCV/HIV-1 co-infection ZEPATIER for 12 or 16 weeks ZEPATIER + RBV for 12 or 16 weeks C-SALVAGE GT 1 TE with HCV protease inhibitor regimen with or without cirrhosis ZEPATIER + RBV for 12 weeks Differene Zepatier (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; January 2016.

Evidence: Percentage with sustained virologic response at 12 weeks (SVR12) with ZEPATIER Trial Genotype All GT-1A GT-1b GT-4 C-EDGE TN 99% 92% 98% 100%a C-SURFER 94% 97% C-EDGE TE ZEPATIER 90% 100% 78% ZEPATIER + RBV 95% C-SALVAGE 96% Difference a Combination of results from C-SCAP, C_EDGE TN, and C_EDGE COINFECTION trials Zepatier (elbasvir and grazoprevir) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; January 2016.

Evidence: Treatment naive patients with HCV genotype 1 and 4 with or without cirrhosis Recommended Treatment experienced patients with HCV genotype 1 and 4 with or without cirrhosis Differene American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. Updated July Accessed Aug

Sofosbuvir and velpatasvir (Epclusa®)
Indication: Treatment of chronic hepatitis C virus (HCV) genotypes 1 – 6 infection Without cirrhosis or with compensated cirrhosis With decompensated cirrhosis for use in combination with ribavirin Approval Date: June 28, 2016 MOA: Sofosbuvir binds to HCV nonstructural protein 5A (NS5A) and inhibits viral RNA replication and virion assembly Velpatasvir, prodrug, inhibits NS5B RNA-dependent RNA polymerase and acts as a chain terminator Dose: One tablet (sofosbuvir 400 mg/velpatasvir 100 mg) once daily with or without food Difference Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2016.

Adverse Effects: Fatigue, headache, increased serum lipase, increased creation phosphokinase, and increased indirect serum bilirubin Interactions: Amiodarone – sofobuvir may enhance bradycardic effect – avoid combination P-gp inducers – may reduce therapeutic effects of sofosbuvir/velpatasvir – avoid combination CYP2B6, CYP2C8, and CYP3A4 inducers (strong) – may reduce therapeutic effects of sofosbuvir/velpatasvir – avoid combination Differene Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2016.

Evidence: Trial Population Study Arms and Duration ASTRAL-1 Genotype 1, 2, 4, 5, 6, treatment-naive and treatment- experienced, without cirrhosis or with compensated cirrhosis EPCLUSA 12 weeks ASTRAL-2 Genotype 2, treatment-naive and treatment- experienced, without cirrhosis or with compensated cirrhosis or Sofosbovir plus ribavirin 12 weeks ASTRAL-3 Genotype 3, treatment-naive and treatment- experienced, without cirrhosis or with compensated cirrhosis Sofosbovir plus ribavirin 24 weeks ASTRAL-4 Genotype 1-6, treatment-naive and treatment- experienced, without cirrhosis or with compensated cirrhosis EPCLUSA 24 weeks Differene Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2016.

Evidence: Percentage with sustained virologic response at 12 weeks (SVR12) with EPCLUSA Trial Genotype All GT-1A GT-1b GT-2 GT-3 GT-4 GT-5 GT-6 ASTRAL-1 99% 98% 100% 97% ASTRAL-2 ASTRAL-3 95% ASTRAL-4 94% 85% * Differene * No subjects with genotype 5 or 6 HCV were treated with EPCLUSA with ribavirin for 12 weeks. Epclusa (sofosbuvir and velpatasvir) [prescribing information]. Foster City, CA: Gilead Sciences Inc; June 2016.

Place in Therapy: Treatment naive patients with HCV genotype 1, 2, 3, 4, 5, and 6 with or without cirrhosis Recommended Treatment experienced patients with HCV genotype 1, 2, 3, 4, 5, and 6 with or without cirrhosis Differene American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. Updated July Accessed Aug

Chronic Hepatitis C Virus (HCV) Therapies
Price (AWP): Drug Unit Size (Price) Treatment Price; 12 weeks Daclatasvir (Daklinza®) 28 tablets ($25,200.00)a $75,600.00 Elbasvir and grazoprevir (Zepatier®) 14 tablets ($10,920.00) $65,520.00 Sofosbuvir and velpatasvir (Epclusa®) 28 tablets ($29,904.00) $89,712.00 Differene aAll 3 strengths (30, 60, and 90 mg)

Infectious Disease Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya®)

Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (Genvoya®)
Indication: Treatment of HIV-1 infection in adults and children (≥12 years) Approval Date: November 5, 2015 MOA: Elvitegravir (Integrase Inhibitor): prevents integration of the proviral gene into human DNA Cobicistat (CYP450 Inhibitor): enhances systemic exposure to elvitegravir Emticitabine (Reverse Transcriptase Inhibitor; Nucleoside) and Tenofovir (Reverse Transcriptase Inhibitor; Nucleotide): interfere with DNA polymerase activity; inhibit viral replication Dose: One tablet once daily Tablet: Elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; March 2016.

Black Box Warning: Lactic acidosis and severe hepatomegaly with steatosis Post treatment acute exacerbation of hepatitis B Adverse Effects: Headache, fatigue, increased (HDL, LDL, Cholesterol, and Triglycerides), nausea, and decreased bone mineral density Interactions: CYP3A4 inhibitors (strong) - avoid combination Lactic acidosis: have been reported with the use of nucleoside analogs in combination with other antiretrovirals Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; March 2016.

Evidence: Two, randomized, double-blinded, non-inferiority trials (n=1733) 1:1 randomization to receive Genvoya or Stribilda once daily Results: Genvoya was non-inferior to Stribild for the number of patients having a plasma HIV-1 RNA less than 30 copies per mL at week 48 Genvoya – 92% Stribild – 90% Adjusted difference: 2.0%, 95% CI -0.7 to 4.7 Adverse events: Genvoya vs Stribild at 48 weeks Significantly smaller mean serum creatinine increases (0.08 vs 0.12 mg/dL; p<0.0001) Significantly less proteinuria (median % change -3 vs 20; p<0.0001) Significantly smaller decrease in bone mineral density Spine (mean % change -1.3 vs -2.86; p<0.0001) Hip (mean % change vs -2.95; p<0.0001) a Stribild = Elvitegravir 150 mg, Cobicistat 150 mg, Emtricitabine 200 mg, and Tenofovir Disoproxil Fumarate 300 mg Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; March 2016.

Price (AWP): 30 tablets - $ Comparator: Stribild® (30) - $ Place in Therapy: Used in patients with no antiretroviral treatment history Replace current antiretroviral regimen in patients who are: Virologically-suppressed (HIV-1 RNA > 50 copies per mL) On stable antiretroviral regimen for at least 6 months No history of treatment failure NO history of resistance to elvitegravir, cobicistat, emtricitabine, or tenofovir alafenamide Lactic acidosis: have been reported with the use of nucleoside analogs in combination with other antiretrovirals Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide) [prescribing information]. Foster City, CA: Gilead Sciences; March 2016.

Other Lesinurad (Zurampic®) Lifitegrast (Xiidra®) Rolapitant (Varubi®)

Lesinurad (Zurampic®)
Indication: Gout, in combination with a xanthine oxidase inhibitor (XOI) for hyperuricemia Approval Date: December 22, 2015 MOA: Selective uric acid reabsorption inhibitor; acts by inhibiting the urate transporter URAT1 URAT 1 is responsible for the majority of renal reabsorption of uric acid (less reabsorption leads to more excretion of uric acid) Dose: 200 mg PO once daily in combination with a XOI (i.e. allopurinol or febuxostat); take in AM w/ food + water Zurampic (lesinurad) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP: January 2016.

Black Box Warning: Acute renal failure has occurred and was more common when lesinurad was given alone Should be used in combination with XOI Adverse Effects: Headache, influenza, blood creatinine increased, gastroesophageal reflux disease Do not initiate/discontinue if CrCl is persistently < 45 mL/min Interactions: CYP2C9 (strong) - decrease metabolism of lesinurad Valproate products - increases serum concentration of lesinurad (avoid combination) Contraindicated in CrCl <30 mL/min Zurampic (lesinurad) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP: January 2016.

Evidence: Three, multicenter, randomized, double-blinded, placebo-controlled clinical trials (n=1537) Serum uric acid levels were reduced in patients in lesinurad arm vs. placebo Place in Therapy: Second-line treatment option for gout if insufficient response to XOI alone Price (AWP): Not available Benefits over Probenecid (the other uricosuric drug): Less drug-drug interactions, once-daily (vs. BID) dose Probenecid price: 500mg (100): $114.56 Zurampic (lesinurad) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP: January 2016.

Lifitegrast (Xiidra®)
Indication: Treatment of the signs and symptoms of dry eye disease Approval Date: July 11, 2016 MOA: Binds to the integrin lymphocyte function-associated antigen-1 (LFA-1) and blocks the interaction of LFA-1 with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) Dose: One drop into each eye every 12 hours Supplied as a 5% ophthalmic solution Xiidra (lifitegrast) [prescribing information]. Lexington, MA: Shire US Inc; June 2016.

Adverse Effects: Eye irritation or discomfort and blurred vision Remove contact lens prior to administration and wait 15 minutes before reinserting Interactions: No know interactions Xiidra (lifitegrast) [prescribing information]. Lexington, MA: Shire US Inc; June 2016.

Evidence: Four, 12-week, randomized, multi-centered, double-blinded, placebo- controlled trials (n=1181) Results: Lifitegrast resulted in a larger reduction in eye dryness score from baseline compared to placebo in all four trials at day 42 and day 84 Price (AWP): Not available Comparator: Cyclosporine (Restasis®): 0.05% Ophthalmic emulsion – $8.53/dose Add price info Xiidra (lifitegrast) [prescribing information]. Lexington, MA: Shire US Inc; June 2016.

Rolapitant (Varubi®) Indication: Prevention of delayed phase chemotherapy-induced nausea and vomiting (emesis) Approval Date: September 2, 2015 MOA: Selectively and competitively inhibiting the substance P/neurokinin 1 (NK1) receptor Dose: Highly emetogenic chemotherapy: 180 mg on day 1 In combination with dexamethasone on days 1, 2, 3, and 4 and a 5-HT3 antagonist on day 1 Moderately emetogenic chemotherapy: 180 mg on day 1 In combination with dexamethasone on day 1 and a 5-HT3 antagonist (if needed) Varubi (rolapitant) [prescribing information]. Waltham, MA: Tesaro Inc; September 2015.

Rolapitant (Varubi®) Adverse Effects: Dizziness and decreased appetite
Interactions: CYP2D6 substrates - rolapitant may increase serum concentrations Rolapitant’s inhibition of CYP2D6 may persist for 7 or more days P-glycoprotein substrates - rolapitant may increase serum concentrations CYP3A4 inducers (strong) - may decrease the efficacy of rolapitant Substrate of CYP3A4 (major); Inhibits BCRP, CYP2B6 (weak), CYP2C8 (weak), CYP2D6 (moderate), P-glycoprotein Varubi (rolapitant) [prescribing information]. Waltham, MA: Tesaro Inc; September 2015.

Rolapitant (Varubi®) Evidence
Two, multicenter, randomized, double-blinded, parallel group trials (n=532) Patients randomized to receive either rolapitant, PO dexamethasone, IV greanisetron or placebo, PO dexamethasone, IV greanisetron on day 1 (PO dexamethasone was given on days 2-4 in both treatment arms) Results: Significantly greater proportion of patients in the rolapitant group had complete responses in the delayed phase than did patients in the placebo group (OR 1.9, 95% CI ; p=0.0006) Incidence of adverse events was similar between both groups Rolapitant in combination with a 5-HT3 receptor antagonist and dexamethasone is well-tolerated and shows superiority over active control for the prevention of chemotherapy-induced nausea and vomiting during the at-risk period (120 h) after administration of highly emetogenic cisplatin-based chemotherapy Varubi (rolapitant) [prescribing information]. Waltham, MA: Tesaro Inc; September 2015.

Rolapitant (Varubi®) Price (AWP): Comparators:
90 mg (2) tablets - $636.00 Comparators: Aprepitant (Emend®): Dosing: 125 mg day 1, then 80 mg day 2 and 3 40 mg (1) - $117.26 80 mg (2) - $434.74 80 & 125 mg (3) - $769.32 125 mg (6) - $ Fosaprepitant (Emend®): Dosing: 150 mg on day 1 Price (AWP): IV solution 150 mg (1) - $336.72 Varubi (rolapitant) [prescribing information]. Waltham, MA: Tesaro Inc; September 2015.

Oncology

Antineoplastic Agents
Generic Name Brand Name Approval Date Indication Atezolizumab Tecentriq® 5/18/16 Urothelial carcinoma Venetoclax Venclexta® 4/11/16 Chronic lymphocytic leukemia Alectinib Alecensa® 12/11/15 ALK-positive lung cancer Elotuzumab Empliciti® 11/30/15 Multiple myeloma (treatment failure with 1 or more previous agents) Necitumumab Portazza® 11/24/15 Advanced squamous non-small cell lung cancer (have not received prior treatment for advanced disease) Ixazomib Ninlaro® 11/20/15 Multiple myeloma (treatment with 1 or more previous agents) Daratumumab Darzalex® 11/16/15 Multiple myeloma (treatment failure with at least 3 previous agents) Osimertinib Tagrisso® 11/13/15 Non-small cell lung cancer Cobinetinib Cotellic® 11/10/15 Advanced melanoma in combination w/vemurafenib Trabectedin Yondelis® 10/23/15 Advanced soft tissue sarcomas Trifluridine/ tipiracil Lonsurf® 9/22/15 Advanced colorectal cancer Sonidegib Odomzo® 7/24/15 Locally advanced basal cell carcinoma

Rare Diseases/ Indications

Rare Disease/Indications
Generic Name Brand Name Approval Date Indication Gallium Ga68 dotatate NETSPOT® 6/1/16 Diagnostic imaging agent to detect rare neuroendocrine tumors Fluciclovine F18 Axumin® 5/27/16 Diagnostic imaging agent to detect recurrent prostate cancer Obeticholic acid (Ocaliva®) Treatment of primary biliary cholangitis (PBC) in combination with ursodiol Defibrotide sodium Defitelio® 3/30/16 Treatment of hepatic veno-occlusive disease following hematopoietic stem cell transplant Obiltoxaximab Anthim® 3/18/16 Treatment of inhalational anthrax Sugammadex Bridion® 12/15/15 Reverse effects of neuromuscular blocking drugs used during surgery Sebelipase alfa Kanuma® 12/8/15 Treatment of lysosomal acid lipase (LAL) deficiency Asfotase alfa Strensiq® 10/23/15 Treatment of perinatal, infantile and juvenile-onset hypophosphatasia (HPP) Uridine triacetate Xuriden® 9/4/15 Treatment of hereditary orotic aciduria

New Dosage Forms

New Dosage Forms - 2016 Generic Name Brand Name Description
Amphetamine Adzenys XR-ODT® Orally disintegrating extended-release formulation for ADHD Glycopyrrolate/formoterol Bevespi Aerosphere® New combination LAMA/LABA inhaler for COPD Acetylcysteine Cetylev® Effervescent tablet for oral solution formulation for acetaminophen overdose Emticitabine/ tenofovir alafenamide Descovy® New combination oral tablet for HIV-1 infection Emticitabine/rilpivirine/ Odefsey® Sumatriptan Onzetra Xsail® Nasal powder inhalation for acute migraine treatment Ciprofloxacin/fluocinolone Otovel® Combination otic solution for acute otitis media in patients wit tympanostomy tubes Tofacitinib Xeljanz XR® Extended-release tablet formulation for rheumatoid arthritis Oxycodone Xtampza ER® New opioid formulation for chronic, severe pain Zembrace SymTouch® New injectable formulation for acute migraine treatment

Conclusion Majority of new drugs discussed are second- or third-line treatment options Not included in guideline recommendations Come at a price $$$ Consideration when making formulary decision Study not guaranteed Some agents require REMS Program

Question #1 Which of the following is indicated for Cystic Fibrosis?
Selexipag Lumacaftor/ivacaftor Cariprazine Filbanserin

Question #2 Which of the following new injectable medications is used only for type 2 diabetes? Lixisenatide Insulin aspart Tresiba Filbanserin

Questions

New Drug Update 2015 – 2016 Rachael McCaleb, PharmD
Assistant Professor, Department of Pharmacy Practice University of Arkansas for Medical Sciences College of Pharmacy Clinical Consultant United States Food and Drug Administration National Center for Toxicological Research

New Drug Update 2015 – 2016 Rachael McCaleb, PharmD

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New Drug Update 2015 – 2016 Rachael McCaleb, PharmD

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