4/19/16 2015 FDA Approvals • 45 novel drugs approved in 2015 • 16 of the 45 (36%) are First-in-Class approvals • 47% of drugs approved to treat rare or “orphan” New Prescription Meds diseases (< 200,000 Americans) You Should Know • 14 drugs (31%) were Fast Track approvals • Many other approvals for new formulations Sally Haack, PharmD http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM485053.pdf Drake University College of Pharmacy & Health Sciences April 19, 2016 Today’s Update Diabetes • Diabetes • Psychiatry • Cardiovascular • Hepatitis C • Respiratory • Miscellaneous 1 4/19/16 Insulin Glargine: Basaglar Insulin Glargine: Basaglar • Approved by FDA in December 2015 • Eli Lilly and Company and Boehringer Ingelheim Pharmaceuticals, Inc • Indication: basal insulin to control high blood glucose in type 1 or type 2 diabetes • Available in US starting December 2016 • Administration: subcutaneously once daily (U-100; 3 mL pen) www.basaglar.com Diabetes, Obesity and Metabolism 17:734-741, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm477734.htm Insulin Glargine: Basaglar Insulin Glargine: Toujeo • Approved by FDA in February 2015; available in April 2015 • Sanofi – Aventis: makers of Lantus • Indication: basal insulin approved for adults with type 1 or type 2 diabetes • Available in a SoloStar pen; 300 units/mL – No conversion necessary between Lantus and Toujeo – Less volume per injection – Gradual release in a compact depot of insulin – different than Lantus; may lead to >24 hour duration of action Diabetes, Obesity and Metabolism 17:734-741, 2015. Insulin Glargine: Toujeo Insulin Glargine: Toujeo Mean HbA1c at 12 months: 7.62 (1.03)% in the Gla-300 group and 7.64 (1.21)% in the Gla-100 group Diabetes, Obesity and Metabolism 17:1142-1149. 2 4/19/16 Insulin Degludec: Tresiba Insulin Degludec: Tresiba • Approved by FDA in September 2015 • Novo-Nordisk • Indication: once-daily, long acting basal insulin approved to control blood sugar in adults with diabetes • Administration: subcutaneously via FlexPen • Available in U-200 and U-100 concentrations • U-200 ~ 600 units/pen; max of 160 units/dose • Ryzodeg 70/30 (insulin degludec/insulin aspart injection) Diabetes Care 35:2464–2471, 2012 Insulin Degludec: Tresiba Psychiatry Diabetes Care 36:2536–2542, 2013 Vraylar (cariprazine) Vraylar (cariprazine) • Approved by FDA in September 2015 • Allergan: Forest Laboratories • Indication: atypical antipsychotic for schizophrenia or bipolar mania • Administration: orally once daily {bipolar 3-6 mg daily; schizophrenia 1.5-6 mg daily} • Adverse drug reactions – EPS, akathisia • Drug interactions with other CYP3A4 inhibitors – Reduce Vraylar dose by half • Monitoring Schizophrenia Research 152 (2014) 450–457 3 4/19/16 Rexulti (brexpiprazole) Rexulti (brexpiprazole) • FDA approved in July 2015 • Otsuka America Pharmaceutical, Inc. • Indication: atypical antipsychotic for major depressive disorder or schizophrenia • Administration: orally once daily {MDD 0.5-3 mg daily; schizophrenia 1-4 mg daily} • Adverse drug reactions – Weight gain and akathisia • Drug interactions and monitoring J Clin Psychiatry 2015;76(9):1232–1240 Aristada (aripiprazole) Cardiovascular • FDA approved October 2015 • Alkermes • Indication: extended-release atypical antipsychotic for schizophrenia • Administration: IM (gluteal or deltoid muscle) once monthly – Available as 441 mg, 662 mg, 882 mg – Must continue oral aripiprazole for 21 days after receiving initial IM dose Entresto (sacubitril/valsartan) Entresto (sacubitril/valsartan) • FDA approved in July 2015 • Novartis • Indication: patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction • Administration: orally twice daily – Replaces ACE-I or ARB • Most common adverse drug reactions: hypotension, hyperkalemia 4 4/19/16 Entresto (sacubitril/valsartan) Savaysa (endoxaban) PARADIGM – HF Trial • FDA approved in January 2015 • Daiichi Sankyo Co., Ltd. • Indication: factor Xa inhibitor for… – Treatment of DVT or PE following 5-10 days parenteral anticoag – Non-valvular atrial fibrillation • Administration: orally once daily (check CrCl) • Adverse drug reactions: bleeding and anemia N Engl J Med. 2014;371(11):993-1004 PCSK9 Inhibitor Antibody Praluent (alirocumab) • FDA approved in July 2015 • Sanofi-Aventis • Indication: adjunct to diet and statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-cholesterol (LDL-C) • Administration: subcutaneously once every 2 weeks (75 mg initial, may increase to 150 mg) Praluent (alirocumab) Repatha (evolocumab) • FDA approved in August 2015 • Amgen • Indication: use in addition to diet statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), homozygous familial hypercholesterolemia (HoFH), or clinical atherosclerotic cardiovascular disease • Administration: subcutaneously 140 mg every 2 weeks J Clin Endocrinol Metab. 2015 Aug; 100(8): 3140–3148. 5 4/19/16 Repatha (evolocumab) Hepatitis C JAMA. 2014;311(18):1870-1883. Zepatier (elbasvir + grazoprevir) Daklinza (daclatasvir) • FDA approved January 2016 • Approved by FDA in July 2015 • Merck • Bristol-Myers Squibb • Indication: treat HCV genotypes 1 & 4, with or without ribavirin • Indication: treat HCV genotype 1 & 3 infection, • Administration: one tablet PO daily with or without with sofosbuvir (Sovaldi) food • Administration: 60 mg PO daily x 12 weeks – Duration depends on genotype, 12-16 weeks • Adverse drug reactions: fatigue, headache, • Adverse drug reactions: fatigue, headache, nausea nausea, diarrhea • Do not use in moderate-severe • Avoid use with amiodarone hepatic impairment Technivie Respiratory (ombitasvir, paritaprevir and ritonavir) • Approved by FDA in July 2015 • AbbVie • Indication: in combination with ribavirin for genotype 4 HCV without cirrhosis • Administration: 2 tablets PO qam with food x 12 weeks • Contraceptives containing ethinyl estradiol must be d/c’d prior to starting therapy 6 4/19/16 Stiolto (tiotropium + olodaterol) Stiolto (tiotropium + olodaterol) • Approved by FDA in May 2015 • Boehringer Ingelheim • Indication: maintenance treatment for COPD – Anticholenergic + LABA • Administration: 2 inhalations once daily {Respimat inhaler} • Adverse drug reactions: nasopharyngitis, cough, and back pain Eur Respir J 2015; 45: 969–979 Utibron (indacaterol/glycopyrrolate) Utibron (indacaterol/glycopyrrolate) • Approved by FDA in October 2015 • Novartis • Indication: maintenance treatment for COPD – Anticholenergic + LABA • Administration: inhale the powder contents of one capsule twice daily • Adverse drug reactions: nasopharyngitis and hypertension International Journal of COPD 2015:10 1015–1026 Miscellaneous Viberzi (eluxadoline) • Approved by FDA in May 2015 • Patheon / Forest Labs • Indication: Irritable Bowel Syndrome with Diarrhea • Administration: 100 mg PO BID – 75 mg PO BID if … • No gallbladder, cant’ tolerate 100 mg dose, mild/moderate hepatic impairment • Adverse drug reactions: constipation, nausea, abdominal pain • Contraindicated in severe hepatic impairment, alcoholism 7 4/19/16 Addyi (flibanserin) • Approved by FDA in August 2015 • Sprout Pharmaceuticals • Indication: hypoactive sexual desire disorder in premenopausal women – Works in CNS, “mechanism of action not known” • Administration: 100 mg PO daily hs {REMS} • Adverse drug reactions: dizziness, somnolence, fatigue, nausea, insomnia, dry mouth • Warning: CNS depression & hypotension Summary • Resources – http://www.centerwatch.com/drug-information/fda- approved-drugs/ – http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ DrugInnovation/ucm483775.htm • Difficult to determine acceptance and use of new drugs in practice • Impact of formularies and insurance coverage • Postmarket surveillance efforts • MedWatch: FDA reporting program [email protected] 8 .