Disclosures. Pharmacist Objectives. Technician Objectives. Definitions. Definitions. New Drug & Therapies Update 11/2/17. First-in-Class Drug

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1 Disclosures New Drug & Therapies Update No relevant conflicts of interest to disclose No off-label indications will be presented Nicholas Cox, PharmD November 4, 2017 Intensive Outpatient Clinic, University of Utah Health Population Health, University of Utah Medical Group Pharmacist Objectives 1. Describe the indication(s), mechanism of action, evidence for approval, and key counseling points for new drugs/biologics approved by the U.S. Food and Drug Administration (FDA) over the past year 2. Assess the potential role in therapy for new drugs/biologics approved by the FDA over the past year 3. Compare and contrast new drugs/biologics approved by the FDA over the past year to previously existing therapies 4. Explain the factors impacting trends in the number of new drug/biologic approvals Technician Objectives 1. List the brand/generic names and indication(s) of new drugs/ biologics approved by the U.S. Food and Drug Administration (FDA) over the past year 2. Define the following terms: novel drug, first-in-class drug, rare/ orphan disease drugs 3. Explain the factors impacting trends in the number of drug/ biologic approvals Definitions New Drug / New Biologic Definition: medication approved by the FDA s Center for Drug Evaluation and Research (CDER) whose active chemical structures have not been approved previously Synonyms: New Molecular Entity (NME) Definitions First-in-Class Drug Definition: medication approved by the FDA s Center for Drug Evaluation and Research (CDER) whose mechanism of action is different from existing therapies Synonyms: Innovative drug Antonyms: Me-too drug fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm htm. Accessed October 23,

2 Definitions An Historical Perspective Rare/Orphan Disease Drugs Definition: medication approved by the FDA s Center for Drug Evaluation and Research (CDER) whose targeted disease affects 200,000 Americans * NME / BLA Approvals NME/BLA Filings 2016 Review 22 new drugs/biologics 2016 Review 22 new drugs/biologics Orphan Drug 1. Anthim (obiltoxaximab) 2. Defitelio (defibrotide) 3. Exondys 51 (eteplirsen) 4. Lartruvo (olaratumab) 5. Netspot (gallium GA 68-dota-tate) 6. Ocaliva (obeticholic acid) 7. Rubraca (rucaparib) 8. Spinraza (nusinersen) 9. Venclexta (venetoclax) First-in- Class 1. Defitelio (defibrotide) 2. Exondys 51 (eteplirsen) 3. Ocaliva (obeticholic acid) 4. Spinraza (nusinersen) 5. Venclexta (venetoclax) 6. Xiidra (lifitegrast ophthalmic) 7. Zinbryta (daclizumab) 8. Zinplava (bezlotoxumab) 2016 Review 22 new drugs/biologics Why so few? Prescription Drug User Fee Act (PDUFA) 73% part of expedite drug development/review 14 inadequate applications Question #1 Which of the following is a medication whose mechanism of action is different from existing therapies? A. Orphan drug B. First-in-class drug C. New molecular entity D. New drug or biologic blogs.fda.gov/fdavoice/index.php/2017/01/a-review-of-cders-novel-drug-approvals-for Accessed October 23,

3 2016 New Approvals Diabetes GI Oncology Hematology Adlyxin (lixisenatide) Ocaliva (obeticholic acid) Epclusa (sofosbuvir/velpatasvir) Zepatier (elbasvir/grazoprevir) Axumin (fluciclovine F 18) Lartruvo (olaratumab) Netspot (gallium Ga 68-dota-tate) Rubraca (rucaparib) Tecentriq (atezolizumab) Venclexta (venetoclax) Defitelio (defibrotide) Pulmonology Infectious Disease Dermatology Briviact (brivaracetam) Exondys 51 (eteplirsen) Nuplazid (pimavanserin) Spinraza (nusinersen) Zinbryta (daclizumab) Cinqair (reslizumab) Anthim (obiltoxaximab) Zinplava (bezlotoxumab) Eucrisa (crisaborole topical) Taltz (ixekizumab) Ophthalmology Xiidra (lifitegrast ophthalmic) Diabetes Type 2 diabetes Adlyxin (lixisenatide) Glucagon-like peptide-1 (GLP-1) agonist Increases glucose-dependent insulin release Decreases glucagon secretion Slows gastric emptying GetGoal program (13 trials) and ELIXA trial reduction in A1C compared to placebo less reduction in A1C compared to exenatide and glulisine CV outcomes: non-inferior to placebo (not superior) 10 mcg subcutaneously once daily for 14 days, then 20 mcg daily BBW/C/W: Pancreatitis ADR: Nausea, GI symptoms, Injection site reactions Administration: Administer within 1 hour before first meal of day Complicated: use medication guides Adlyxin (lixisenatide) injection, for subcutaneous use. Prescribing Information. Sanofi-Aventis. 07/2017. Diabetes Dosing Frequency Mixing Required Additional Indications Nausea Rate Adlyxin (lixisenatide) Bydureon (exenatide) Byetta (exenatide) Tanzeum (albiglutide) Trulicity (dulaglutide) Victoza (liraglutide) QDay QWeek BID QWeek QWeek QDay - Y - Y Weight Loss 25-40% 9-24% 40-44% 11% 12-21% 39% CV Benefit Y GLP-1 Agonists Second-line after metformin; some argue for first-line status Adlyxin (lixisenatide) Not first-line GLP-1 agonist, but third-party payers will dictate Adlyxin (lixisenatide) injection, for subcutaneous use. Prescribing Information. Sanofi-Aventis. 07/2017. Standards of Medical Care in Diabetes. American Diabetes Association Hepatitis C Epclusa (sofosbuvir/velpatasvir) Zepatier (elbasvir/grazoprevir) Hepatitis C (all 6 genotypes) Hepatitis C (genotypes 1, 4) Sof: HCV NS5B-P inhibitor Vel: HCV NS5A inhibitor ASTRAL-1, -2, -3, -4 Trials G1-G6 SVR Rate: 94-99% Elb: HCV NS5A inhibitor Gra: HCV NS3/4A-Pr inhibitor G1 SVR Rate: 94-97% G4 SVR Rate: % 1 tablet (400/100 mg) PO daily x 12W 1 tablet (50/100 mg) PO daily x 12-16W Notes Cost: $75,000 for 12-week course Cost: $55,000 for 12-week course Zepatier (elbasvir/grazoprevir) tablets, for oral use. Prescribing Information. Merck and Co. 02//2017. Epclusa (lixisenatide) tablets, for oral use. Prescribing Information. Gilead Sciences. 08/2017. hepatitisc.uw.edu/page/treatment/drugs. Accessed October 23, Hepatitis C Epclusa (sofosbuvir/velpatasvir) ADR: minimal Headache 22%; Fatigue 15% Antacids: Separate by 4 hours H2RA s: With drug or 12 hours apart ( famotidine 40 mg BID) PPI s: Avoid combo. If needed, take 4 hours before PPI. Only omeprazole 20 mg daily studied Amiodarone, Digoxin: Avoid combo Statins: Monitor statin ADR s; Max of rosu 10 mg Inducers: Avoid combo Administration: With or without food Zepatier (elbasvir/grazoprevir) ADR: minimal Fatigue 11%; Headache 10% Nafcillin, Ketoconazole: Avoid combo Tacrolimus: tacro monitoring Statins: Monitor statin ADR s; Max of rosu 10 mg or atorva 20 mg Modafanil: Avoid combo Administration: With or without food Hepatitis C Epclusa Zepatier Helpful option for G3 patients, particularly because: IFN-free and relatively economical Ribavirin-free for compensated cirrhosis Helpful option G1 and G4 patients, particularly because: for treatment-naïve and treatment-experienced patients in severe renal impairment Zepatier (elbasvir/grazoprevir) tablets, for oral use. Prescribing Information. Merck and Co. 02//2017. Epclusa (lixisenatide) tablets, for oral use. Prescribing Information. Gilead Sciences. 08/2017. hepatitisc.uw.edu/page/treatment/drugs. Accessed October 23, Zepatier (elbasvir/grazoprevir) tablets, for oral use. Prescribing Information. Merck and Co. 02//2017. Epclusa (lixisenatide) tablets, for oral use. Prescribing Information. Gilead Sciences. 08/2017. hepatitisc.uw.edu/page/treatment/drugs. Accessed October 23, hcvguidelines.org. Accessed October 23,

4 Other Briviact (brivaracetam) Adjunct for partial-onset seizures Unknown; possibly related to synaptic vesicle protein 2A (SV2A) affinity 23% reduction in partial-onset seizures compared to placebo 50 mg PO BID initially; dosing range of mg/day BBW/C/W: CNS depression, neutropenia, hypersensitivity, psych ADR: Fatigue/dizziness 20-27%; Malaise 20-27%; 13% psychiatric disturbance Rifampin: double Briviact dose Anticonvulsants: varies often requires dose adjustments Administration: With or without food; do not chew/crush Schedule V (euphoria) Nuplazid (pimavanserin) Hallucinations/delusions associated with Parkinson s disease psychosis Selective serotonin inverse agonist (SSIA) Targets 5-HT2A receptor Avoids dopamine! To be determined; marketed as Keppra with less irritability Briviact (brivaracetam) tablets, for oral use. Prescribing Information. UCB, Inc. 09/2017. Nuplazid (pimavanserin) tablets, for oral use. Prescribing Information. Acadia. 04/2017. urmc.rochester.edu/neuroslides/slide199.html. Accessed October 23, Treatments for Non-Motor Symptoms. International Parkinson and Movement Disorder Society Nuplazid (pimavanserin) Hallucinations/delusions associated with Parkinson s disease psychosis Selective serotonin inverse agonist (SSIA) Targets 5-HT2A receptor Avoids dopamine! 6-week trial vs placebo: decreased frequency & severity of hallucinations/ delusions without worsening PD motor symptoms 34 mg PO daily; dose adjustments for CYP-3A4 inhibitors/inducers BBW/C/W: Dementia-related psychosis, CNS depression, orthostasis, QT prolongation ADR: Minimal QT-prolonging agents: Avoid combo CYP-3A4 Inhibitors: 17 mg daily CYP-3A4 Inducers: 34 mg daily with possible increased dose Administration: With or without food Nuplazid (pimavanserin) tablets, for oral use. Prescribing Information. Acadia. 04/2017. Decreasing hallucinations & delusions Maintaining motor symptom control Dermatology Eucrisa (crisaborole topical) Mild-moderate atopic dermatitis Indicated for adults and children > 2 years of age Monoclonal antibody that inhibits phosphodiesterase-4 (PDE-4) Increased clear/almost-clear skin after 28 days compared to vehicle-only Thin layer topically to affected areas BID BBW/C/W: Hypersensitivity ADR: Minimal Strategies: 1. Decrease dopaminergic therapies (levodopa, dopamine agonists) 2. Initiate antipsychotics (pimvanserin > quetiapine > clozapine) Nuplazid (pimavanserin) tablets, for oral use. Prescribing Information. Acadia. 04/2017. Treatments for Non-Motor Symptoms. International Parkinson and Movement Disorder Society To be determined; not addressed in guidelines Eucrisa (crisaborole) ointment, 2%, for topical use. Prescribing Information. Anacor. 12/

5 Dermatology Taltz (ixekizumab) Notes Moderate-severe plaque psoriasis Monoclonal antibody IgG4 that targets/neutralizes IL-17A UNCOVER-2, -3 Trials Clearly superior to placebo Increased attainment of PASI 90 (64% vs 18%) and PASI 100 (34% vs 4%) compared to etanercept 160 mg subcutaneously once, then 80 mg Q2W x 6 doses, then 80 mg Q4W BBW/C/W: Hypersensitivity, Infections 26-57%, IBD ADR: Injection site reaction 17%, Neutropenia 11% Concurrent immunosuppressive; vaccines Administration: Rotate anatomical sites: upper arms, thighs, or abdomen TB screening prior to therapy; ensure immunizations up-to-date prior to therapy To be determined, possibly first-line for mod-severe plaque psoriasis Taltz (ixekizumab) injection, for subcutaneous use. Prescribing Information. Eli Lilly and Co. 07/2017. Ophthalmology Xiidra (lifitegrast ophthalmic) Dry eye disease Binds integrin lymphocyte function-associated antigen-1 (LFA-1) and prevents LFA-1 and ICAM-1 interaction OPUS-1, -2, -3, and SONATA Trials Improved inferior corneal staining score compared to placebo Instill 1 drop every 12 hours into each eye ADR: Minimal; similar to placebo Administration: Discard single-use containers Wait 15 min afterwards before inserting contacts To be determined; not addressed in guidelines Xiidra (lifitegrast ophthalmic solution) 5%, for topical ophthalmic use. Prescribing Information. Shire. 07/2016. Question #2 Adlyxin (lixisenatide), a recently approved medication to treat type 2 diabetes, has what mechanism of action? A. GLP-1 agonist B. SGLT-2 inhibitor C. DPP-4 inhibitor D. PPAR-gamma agonist Question #3 For Epclusa and Zepatier, which of the following aspects are relatively complicated and an opportunity for the pharmacist to help manage? A. Side effects B. Drug-drug interactions C. Dosing D. Administration Question #4 What is the unique advantage that Nuplazid (pimavanserin) provides in treating hallucinations and delusions in Parkinson s disease (PD)? A. Long half-life allows for once weekly dosing B. Superior efficacy compared to quetiapine C. Relatively minimal drug interactions D. Does not worsen PD motor symptoms Other 2016 Approvals Drug Indication Notes Anthim (obiltoxaximab) Inhalational anthrax exposure Axumin (fluciclovine F 18) Prostate cancer Diagnostic imaging agent Cinqair (reslizumab) Asthma (eosinophlilic phenotype) Defitelio (defibrotide) Hepatic veno-occlusive disease Orphan/Rare-Disease Exondys 51 (eteplirsen) Duchenne muscular dystrophy Orphan/Rare-Disease Lartruvo (olaratumab) Soft-tissue sarcoma Netspot (gallium Ga 68-dota-tate) Neuroendocrine tumors Diagnostic imaging agent Ocaliva (obeticholic acid) Primary biliary cholangitis Orphan/Rare-Disease Rubraca (rucaparib) Ovarian cancer Spinraza (nusinersen) Spinal muscular atrophy Orphan/Rare-Disease Tecentriq (atezolizumab) Urothelial carcinoma Venclexta (venetoclax) Chronic lymphocytic leukemia (CLL) Orphan/Rare-Disease Zinbryta (daclizumab) Multiple sclerosis Zinplava (bezlotoxumab) Clostridium difficile infection 5

6 2017 Notables Drug Baxdela (delafloxacin) Bevyxxa (betrixaban) Dupixent (dupilumab) Siliq (brodalumab) Symproic (naldemedine) Tremfya (guselkumab) Xadago (safinamide) Indication Acute bacterial skin infections VTE prevention Atopic dermatitis Plaque psoriasis Opioid-induced constipation Plaque psoriasis Parkinson s disease Safety Communications 09/20/17: Avoid withholding opioid addition medications (ie, methadone, buprenorphine) in patients concurrently taking benzodiazepines or CNS depressants 09/06/17: Separate Kayexalate from all oral medications by at least 3 hours 05/16/17: Canagliflozin causes increased risk of leg and foot amputations 04/20/17: Avoid codeine and tramadol products in children (< 18 years of age) and breastfeeding mothers fda.gov/drugs/drugsafety/ucm htm. Accessed October 23, Safety Communications 02/02/17: Rare but serious allergic reaction with chlorhexidine gluconate 12/16/16: Revision of mental health side effects of smoking cessation agents, varenicline and bupropion, to reflect clinical findings 12/14/16: Pioglitazone associated with increased risk of bladder cancer 10/04/16: Hepatitis B virus reactivation in patients treated with direct-acting antiviral medications for hepatitis C New Drug & Therapies Update Nicholas Cox, PharmD November 4, 2017 Intensive Outpatient Clinic, University of Utah Health Population Health, University of Utah Medical Group fda.gov/drugs/drugsafety/ucm htm. Accessed October 23,