8/31/2016 Disclosures • Both presenters have nothing to disclose. New Drug Updates Lalita Prasad‐Reddy, PharmD, MS, BCACP, BCPS, CDE Clinical Assistant Professor Chicago State University College of Pharmacy Diana Isaacs, PharmD, BCPS, BC‐ADM, CDE Clinical Pharmacy Specialist Cleveland Clinic Diabetes Center September 16, 2016 Pharmacist Objectives Technician Objectives • Describe the place in therapy and mechanisms of action • Describe the place in therapy and mechanisms of of newly approved drugs in the last 15 months. action of newly approved drugs in the last 15 months. • Compare newly approved agents from current agents utilized in the management of disease. • Compare newly approved agents from current agents utilized in the management of disease. • Describe newly approved agents in terms of their place in therapy, effectiveness, safety, and patient administration. • Describe newly approved agents in terms of their place in therapy, effectiveness, safety, and patient administration. • Summarize important patient counseling pearls for newly approved agents for the management of disease. New Drug Stats New Drugs & Disease States • From 2006‐2014 • Diabetes • Heart Failure – – – Average 28 novel drugs approved/year Insulin degludec (Tresiba®) Sacubitril/valsartan (Entresto®) – Lixisenatide (Adlyxin®) – Ivabradine (Corlanor®) • In 2015, 45 novel drugs approved • Gout • Asthma – 16 (36%) are first‐in‐class (ex. Praxbind®) – Lesinurad (Zurampic®) – Reslizumab (Cinqair®) – 21 (47%) to treat rare/orphan diseases (ex. Kanuma®) – Mepolizumab (Nucala®) – 29 (64%) approved in the US before other countries (ex. • Bleeding reversal Entresto®) – Idarucizumab (Praxbind®) • Hepatitis C – Sofosbuvir/velpatasvir (Epclusa®) • Hyperlipidemia • In 2016 (as of July) – Elbasvir/grazoprevir (Zepatier®) – Evolocumab (Repatha®) – Daclatasvir (Daklinza®) – 16 novel drugs approved – Alirocumab (Praluent®) Novel Drugs Summary 2015. Available at: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm474696.htm. Accessed August 8th, 2016 1 8/31/2016 The Ideal Basal Insulin Insulin Degludec (Tresiba®) • Indications for Insulin Degludec (Ideg) Possess a peakless profile – Improve glycemic control in adults with diabetes mellitus Deliver a consistent and reliable rate of absorption • Provide less variability in coverage among all populations FDA approved September, 2015 Cause no weight gain or hypoglycemia • Specifics – After injection, Ideg dihexamers join together creating Provide a true 24 –hour coverage following a single injection long, soluble multiheximer chains that prolong duration of action – Compared to glargine, exhibits equivalent of even Allow mixing of basal/bolus insulins in same injection syringe superior glycemic control – Available in U‐100 and U‐200 formulations Tresiba Pacakge Insert, NovoNordisk, 2015 A Comparison of Kinetics Tresiba® Clinical Data Property Glargine Glargine Degludec Study Design Intervention Results: Efficacy (U-300) (U-100) Fifty‐two weeks, Adults with type 2 diabetes Insulin degludec and insulin glargine decreased mean randomized, controlled, inadequately A1C concentrations from baseline by 1.06 and 1.19%, Onset 64-51 –2 open‐label, multi‐ controlled with oral glucose lowering respectively, with an estimated treatment difference of national, parallel design, agents were randomized to 0.09% (95% CI –0.04 to 0.22%), indicating that (hours) treat‐to‐target, non‐ insulin degludec (n = 773) or insulin degludec was noninferior to insulin glargine. Rates of inferiority trial glargine (n = 257) once daily, both in hypoglycemia were similar, with nocturnal Duration of 24-36 24 > 42 combination with metformin. hypoglycemia and severe hypoglycemia occurring less Action frequently (p < 0.05) with degludec. (hours) Fifty‐two weeks, Study B: Adults with type 2 diabetes Insulin degludec and insulin Half-life ~ 19 hours ~ 12 hours 25 hours randomized, controlled, inadequately controlled with glargine decreased mean A1C concentrations by 1.10 open‐label, treat‐to‐ Insulin +/‐ oral agents were and (T1/2) target, multi‐national, randomized to degludec (n = 755) or 1.18%, respectively, with an estimated non‐inferiority trial insulin glargine (n = 251) in treatment difference of 0.08% Time to 5 days 24 hours 3 days combination with aspart before (95% CI –0.05 to 0.21%), meeting criteria for meals, +/‐ metformin and/or noninferiority for degludec. Rates of overall Steady pioglitazone. hypoglycemia and nocturnal hypoglycemia were lower in those treated with insulin Degludec, while rates of State severe hypoglycemia were similar between groups. Lantus pacakge insert, Sanofi, 2000. Diabetes Care 2015 Apr; 38(4): 637‐643 Tresiba Pacakge Insert, NovoNordisk, 2015 Diabetes Care 35:2464–2471, 2012. Lancet 379:1498–1507, 2012. Patient Populations who may Benefit Degludec vs. Glargine from Tresiba® Degludec Glargine • Elderly Can be mixed in one injection Should not be mixed in one syringe with rapid‐acting insulin injection syringe with rapid‐acting • Learning difficulties insulin • Dependent on caretakers or healthcare Day‐to‐day variability of Day‐to‐day variability with absorption is significantly lower glargine seen in multiple patient professionals for insulin administration than glargine populations • Unable to achieve glycemic control despite Flexibility in dosing Requires once to twice daily administration optimized glycemic regimens Overall, Degludec is associated with improved glycemic control overall with less hypoglycemia Lantus pacakge insert, Sanofi, 2000. Diabetes Care 2015 Apr; 38(4): 637‐643 Tresiba Pacakge Insert, NovoNordisk, 2015 2 8/31/2016 Which of the Following is a Lixisenatide (Adlyxin®) Difference Between Insulin • FDA approved: July, 2016 Degludec and Insulin Glargine? • Glucagon‐like‐peptide receptor agonist (GLP‐1 RA) • MOA: improves glycemic control through effects on glucose‐ dependent insulin secretion, glucagon secretion, gastric A. Insulin degludec can be mixed with insulin emptying, and satiety aspart in a syringe • Shorter half‐life (2‐5 hours), more impact on PPG compared B. Insulin degludec can be inhaled with other GLP‐1 RAs C. Insulin glargine causes less hypoglycemia D. Insulin glargine offers more flexibility in dosing Lixisenatide. Micromedex 2.0. Available at: http://www.micromedexsolutions.com. Accessed August, 2016 Lixisenatide: GLP-1 RA Comparison A Me Too Drug? GLP‐1 RA Dosing Schedule CrCL Renal Dose A1c • Safety/effectiveness evaluated in 10 clinical trials (SC) Adjustments Lowering including 5400 patients with type 2 diabetes Albiglutide (Tanzeum®) 30mg‐50mg weekly None ~1% – Superior to placebo Dulaglutide (Trulicity®) 0.75‐1.5mg weekly None ~1.5% – Non‐inferior to exenatide BID and insulin glulisine Exenatide (Byetta®) 5mg‐10mg BID 1‐60 30‐50: use caution ~1% minutes before meals <30: not recommended Study Study Design Results Exenatide extended 2mg weekly 30‐50: use caution ~1.5% GetGoal X 634 patients, open‐label, After 24 weeks, similar reductions in A1C release (Bydureon®) <30: not recommended randomized to lixisenatide 20mcg and FBG. More weight loss with exenatide Liraglutide (Victoza®) 0.6mg dailyx1 week, Mild to severe renal ~1.5% daily or exenatide 10mcg bid. (‐3.98 vs. ‐2.96kg) and fewer GI events with then 1.2‐1.8mg daily impairment: not lixisenatide. recommended GetGoal‐ 896 patients on basal insulin After 26 weeks, lixisenatide non‐inferior to Lixisenatide (Aldyxin®) 10mcg daily x 2 weeks, 30‐50: use caution ~0.9% Duo2 randomized to lixisenatide or glulisine in A1C reduction (‐0.6% vs. ‐0.8%) then 20mg daily, 1 <30: not recommended insulin glulisine. and superior in weight loss (LS mean hour before breakfast difference: ‐1.99kg). PL Detail-Document, Comparison of GLP-1 Agonists. Pharmacist’s Letter/Prescriber’s Letter. December 2014 Lixisenatide. Micromedex 2.0. Available at: http://www.micromedexsolutions.com. Accessed August, 2016 Rosenstock et al. Diabetes Care. 2013 Oct; 36(10):2945‐51., Anderson et al. Ther Adv Chronic Dis. 2016 Jan; 7(1): 4–17. Which of the Following is an In the Pipeline: iGlarLixi Important Patient Counseling • Lixisenatide + insulin glargine in a fixed‐ratio pen Point for Lixisenatide? • Daily dose range: 10‐60 units corresponding to lixisenatide 5‐20mcg A. Take with food to avoid upset stomach B. Do not use if you are already taking insulin C. Common side effects include nausea and diarrhea D. Only needs to be injected once weekly Lixisenatide and Insulin Glargine/Lixisenatide Briefing Document . Available at: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM502559.pdf. Accessed August 11th, 2016 3 8/31/2016 Lesinurad (Zurampic®) Zurampic® Clinical Trials • FDA approved December, 2015 for hyperuricemia in gout • 3 randomized, placebo‐controlled studies • MOA: reduces serum uric acid by inhibiting transporter proteins Drugs Design Results involved in uric acid reabsportion including uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4) Zurampic® + 2 randomized 12 month A greater proportion of patients allopurinol vs. trials (n=1213) treated with Zurampic® combination allopurinol alone achieved UA<6mg/dL compared • Dose: 200mg QAM with food and in combo with a xanthine oxidase with allopurinol alone (54 vs 28% inhibitor and 55 vs 23%). No major differences in gout flares from 6‐12 • Adverse Effects: headache, Scr increase, GERD months. Zurampic® + 1 randomized 12 month More uric acid lowering with • Place in therapy: add on to allopurinol