LUNCH AND LEARN. April 7, CE Activity Information & Accreditation

Transcription

1 LUNCH AND LEARN New Drugs of 2016: Part 1 April 7, 2017 Featured Speaker: Mary Lynn Moody, BSPharm Director, Business Development Drug Information and Prior Authorization Group University of Illinois at Chicago CE Activity Information & Accreditation (Pharmacist and Tech CE) 1.0 contact hour Funding: This activity is self funded through PharMEDium. It is the policy of to ensure balance, independence, objectivity and scientific rigor in all of its continuing education activities. Faculty must disclose to participants the existence of any significant financial interest or any other relationship with the manufacturer of any commercial product(s) discussed in an educational presentation. Ms. Moody has no relevant commercial and/or financial relationships to disclose

2 Online Evaluation, Self-Assessment and CE Credit Submission of an online self assessment and evaluation is the only way to obtain CE credit for this webinar Go to Print your CE Statement online Live CE Deadline: May 5, 2017 CPE Monitor CE information automatically uploaded to NABP/CPE Monitor upon completion of the self assessment and evaluation (user must complete the claim credit step) Attendance Code Code will be provided at the end of today s activity Attendance Code not needed for On Demand 3 Ask a Question Submit your questions to your site manager. Questions will be answered at the end of the presentation. Your question...? 4 2

3 Resources Visit to access: Handouts Activity information Upcoming live webinar dates Links to receive CE credit 5 Mary Lynn Moody BSPharm Clinical Associate Professor Department of Pharmacy Practice University of Illinois at Chicago 6 3

4 Learning Objectives-Pharmacists Describe the new drugs approved by the Food and Drug Administration in 2016 Discuss the role of these agents in therapy Summarize the adverse effects and potential drug interactions of these new agents 7 Learning Objectives- Technicians Describe the new drugs approved by the Food and Drug Administration in 2016 Discuss any unique preparation and/or dispensing requirements for these agents Summarize the adverse effects and potential drug interactions of these new agents that may require pharmacist intervention 8 4

5 New molecular entities (NME) Refer to handout for the next three slides Not a Blockbuster Year 1 22 new molecular entities (NME) Much lower than last year (45) Below average of 29/year 5 approved in 2015 ahead of schedule 75% qualified for at least 1 expedited designation

6 Breakthrough Status 2 This designation authorized by Congress in 2012 Reserved for agents that treat serious or life threatening diseases or conditions or provide substantial improvement over existing therapy FDA will expedite the development and review of these agents This year, 32% (7/22) drugs were awarded that breakthrough status 11 Orphan drugs 2 41% (9/22) approved for orphan diseases Orphan diseases occur in < 200,000 patients in US 25 million total patients in this category Financial incentives, tax credits, fee waivers

7 13 Lixisenatide (Adlyxin) 3 Approved July 27, th glucagon-like peptide-1 (GLP-1) receptor agonist Approved to treat type 2 diabetes mellitus

8 Lixisenatide Pharmacokinetics 4 Administer within one hour prior to the first meal of the day Administer subcutaneously in the abdomen, arm or thigh No difference in rate of absorption Excreted through glomerular filtration Elimination half life: 3 hours 15 Lixisenatide dosing 4,5 Available as 50 mcg/ml, 100 mcg/ml prefilled syringes Dose is 10 mcg once a day subcutaneously for 14 days Increase to 20 mcg if needed Administer within 1 hour prior to the first meal of the day

9 Lixisenatide Efficacy 6 Head to head comparison to exenatide Non-inferior to twice daily exenatide 50% of patients in each group achieved HbA1c < 7% Both drugs exhibited some weight loss Lixisenatide had less hypoglycemia and GI effects 17 Lixisenatide ELIXA trial 7 6,068 diabetic patients with MI or unstable angina (6 mos) Median follow up was 25 months Designed to assess risk for MI, stroke, hospitalization Not associated with difference in cardiovascular outcome compared to placebo

10 Lixisenatide 4,5 Contraindications/Warnings Hypersensitivity/antibody development Pancreatitis risk Renal damage Adverse effects Hypoglycemia in combination with insulin or sulfonylureas Nausea (25%) Vomiting (10%) Headache (9%) Diarrhea (8%) Dizziness (7%) 19 Lixisenatide Place in therapy Crowded market Victoza -market leader for years No cardiovascular benefit like Victoza Some benefit in patients with GI or hypoglycemia with other GLP-1 agents

11 Pharmacist Clinical Points Be sure patient can demonstrate proper use Need a new needle each day Explain what to do if dose is missed, give within hour of next meal Be sure to educate patient about hypoglycemia and how to manage 21 Technician Points Check to see if the patient needs to have the pharmacist review pen activation process Be sure patient has needles and supplies when they pick up medication Notify the pharmacist if the patient does not fill prescription regularly

12 Hepatitis C 8 Paradigm shift since 2011 Direct acting antiviral (DAA) agents Changed approach to care Increased effectiveness In 2014, combination products are an option for an all-oral therapy approach with exceptional efficacy rates (>90%) 23 Hepatitis C 9 Response is measured by sustained virologic response (SVR) No detectable HCV RNA 12 weeks after tx New combinations have SVR rates near 100%

13 25 Elbasvir and grazoprevir (Zepatier) 10 Approved January 28, 2016 Combines 2 DAAs Approved for the treatment of chronic HCV genotype 1 or 4 infection in adults. 70% of HCV cases are genotype 1 in the US

14 Elbasvir and grazoprevir 11 Two different mechanisms of action Work at different steps in the virus lifecycle Extensively bound to plasma proteins (>98.8%) T ½ of elbasvir is 24 hours and 31 hours for grazoprevir Partially eliminated by oxidative metabolism, primarily by CYP3A Primary route of elimination: feces (90%) with less than 1% excreted in urine 27 Elbasvir and grazoprevir dosing 5, 11 Patients should be tested for hepatitis B infection (HBV) and NS5A resistance if genotype 1a The recommended dose-one tablet once a day for 12 weeks No dosage adjustment for renal impairment

15 Dosing duration 11 Patient Type Recommended treatment duration Genotype 1a or 1b:Treatment naïve or previous treatment with peginterferon and ribavirin Genotype 4:Treatment naïve Gentotype 1a and high level NS5A polymorphism Genotype 1a or 1b previously treated with peginterferon, ribavirin and protease inhibitor Genotype 4 previously treated with peginterferon and ribavirin 12 weeks 12 weeks 16 weeks in combination with ribavirin 12 weeks in combination with ribavirin 16 weeks in combination with ribavirin 29 Elbasvir and grazoprevir- Efficacy clinical trials that included both treatment naïve as well as treatment experienced patients C-EDGE patients with genotype 1 or 4 were treated for 12 weeks SVR12 rates were 95% for the genotype1 patients and 100% for the genotype 4 patients

16 Elbasvir and grazoprevir Efficacy 14 Stage 4 and 5 kidney disease (C- SURFER) 122 patients enrolled in the trial SVR12 rate was 94% 31 Elbasvir and grazoprevir 11 Contraindications Moderate to severe liver disease Black Box HBV reactivation risk Screen all patients for HBsAg and anti-hbc before starting treatment

17 Elbasvir and grazoprevir 11 Warnings Elevated liver enzyme called alanine aminotransferase (ALT) 1% of patients Women, Asians, elderly Avoid in severe liver damage No information in pregnancy or lactation 33 Elbasvir and grazoprevir 5,11 Drug Interactions- Contraindicated Anticonvulsants Rifampin St John s Wort Efavirenz HIV medications Cyclosporine

18 Elbasvir and grazoprevir 11 Drug interactions- Warnings Nafcillin, ketoconazole Rosuvastatin, atorvastatin Etravine Tacrolimus 35 Elbasvir and grazoprevir 5,11 Adverse effects Common: nausea, fatigue and headache Rare: Increased ALT levels (1%)

19 Pharmacist Clinical Points Initial detailed counseling session Importance of adherence and the risks of developing resistance Probe for any potential barriers to adherence and address them HBV reactivation: Verify screening was done; Discuss risks of reactivation Review significant drug interactions 37 Technician Tips Make a reminder in the computer to alert pharmacist if the patient does not return for refill Alert pharmacist if the patient is purchasing an OTC product to prevent interactions

20 39 Epclusa 15 Approved June 28, st fixed dose combination for all HCV genotypes First single tablet regimen for genotype 2 and 3 that does not require ribavirin Potential to eliminate need for genotype testing

21 Epclusa Pharmacology 5,16 Sofosbuvir inhibits the HCV NS5B RNAdependent RNA polymerase Velpatasvir inhibits HCV NS5A protein which is necessary for viral replication 41 Epclusa 16 Approved for the treatment of HCV genotypes 1,2,3,4,5,and 6 infections Decompensated cirrhosis: Epclusa and ribavirin All patients should be tested for current or prior HBV infection before starting Epclusa

22 Epclusa dosing 5,16 One tablet once a day for 12 weeks Can be taken with or without food In decompensated cirrhosis, combine Epclusa with ribavirin for 12 weeks No dose recommendation for severe renal impairment Can use standard dose in patients with hepatic impairment 43 Epclusa Efficacy Trial Genotype Results ASTRAL-1 1,2,3,4,5,6 99% vs. placebo ASTRAL % vs 94% (sofosbuvir and ribavirin) ASTRAL % vs 80% (sofosbuvir and ribavirin) ASTRAL-4 (decompensated) 1,2,3,4,5, %

23 Epclusa Warnings 16 HBV reactivation Serious bradycardia Caution when used with ribavirin 45 Epclusa adverse effects 16 Common adverse effects: headache, fatigue, nausea, asthenia and insomnia Less common: rash (2-5%) and depression (1%) Serious symptomatic bradycardia when combined with amiodarone

24 Epclusa drug interactions 16 Serious symptomatic bradycardia when combined with amiodarone Reduced effects of Epclusa Acid blocking/neutralizing drugs Anticonvulsants Rifampin Some HIV drugs, St John s Wort Increased digoxin levels when combined Increase levels of statins when combined 47 Pharmacist Clinical Points Initial detailed counseling session Importance of adherence and the risks of developing resistance Probe for any potential barriers to adherence and address them HBV reactivation: Verify screening was done; Discuss risks of reactivation Review significant drug interactions

25 Technician Tips Make a reminder in the computer to alert pharmacist if the patient does not return for refill Alert pharmacist if the patient is purchasing an OTC product to prevent interactions

26 Eteplirsen 20 Approved September 19, 2016 Accelerated approval pathway as an orphan drug Seventh rare pediatric disease priority review voucher issued Confirmed mutation of the dystrophin gene amenable to exon 51 skipping Which affects about 13% of the population with Duchenne Muscular Dystrophy (DMD) 51 Eteplirsen 21 Antisense oligonucleotide Binds to exon 51 in the RNA that codes for dystrophin Allows skipping of exon 51 Formation of a partially functional dystrophin protein The plasma protein binding of eteplirsen is low (6-17%) Volume of distribution of the drug is 600 ml/kg Primarily excreted through the kidneys and the elimination half-life is 3 to 4 hours

27 Eteplirsen Dosing 5,21 30 mg/kg of body weight once a week Infused over 35 to 60 minutes Dilute in 0.9% sodium chloride to a final volume of 100 to 150 ml Not studied in patients with liver or kidney disease so dose adjustments are not reported 53 Eteplirsen Efficacy 22 FDA Advisory Committee did not support approval Not enough evidence FDA Commissioner interceded and approved the agent in spite of this Pivotal clinical trial included only 12 boys with DMD Surrogate end-point of dystrophin increase in skeletal muscle not clinical improvement Substantial flaws in the initial clinical trial submitted FDA required the manufacturer to conduct additional studies to keep approval

28 Eteplirsen Side Effects 21 Common side effects: Balance (38%) Vomiting (38%) Skin rash (25%) Other adverse effects ( 10%) confusion, arthralgia, severe itching, catheter site pain, and upper respiratory tract infection Rare: transient erythema, facial flushing, and elevated temperature on the days that eteplirsen was administered 55 Pharmacist Clinical Points Limited to Specialty Pharmacies Counsel the parents/guardian of the child Administered intravenously once a week Specialty pharmacy or home compounded? Pharmacists may recommend an anesthetic cream for the infusion

29 Technician Tips Allow vials to warm to room temperature Do not shake Administer immediately, no preservative Dilute in 0.9% sodium chloride only Final volume of 100 to 150 ml Can store final product in refrigerator for 24 hours if needed

30 Bezlotoxumab(Zinplava) 23 October 21, 2016 Fast Track Approval Reduce the recurrence of Clostridium difficile infection (CDI) Use with an antibacterial drug NOT approved to treat CDI 59 Bezlotoxumab 24 Human monoclonal antibody Binds to C. difficile toxin B and neutralizes effect Eliminated by catabolism so no need to adjust dose in renal or liver impairment

31 Bezlotoxumab Dosing 24 Single dose: 10 mg/kg administered as an intravenous infusion Dilute drug with 0.9% sodium chloride or Dextrose 5% in water Final concentration ranges from 1 mg/ml to 10 mg/ml Use a 0.2 to 5 micron in-line filter Administer over 60 minutes. Do not administer IV push or bolus 61 Bezlotoxumab Efficacy 24 MODIFY I and II studies enrolled 2,655 patients Both hospital and outpatient settings Primary endpoint recurrence of CDI within 12 weeks: lower with Zinplava (17.4%, p=0.0003) compared to 27.6% in placebo Higher risk of heart failure in at risk patients

32 Bezlotoxumab Warnings 24 No contraindications Heart failure reported in trials History of heart failure: 12.7% in Zinplava group; 4.8% in placebo group Reserve use when benefit outweighs risk in patients with history of heart failure 63 Bezlotoxumab Adverse Effects 24 Common Infusion related reactions (10%) Nausea (7%) Pyrexia (5%) Headache (4%) Rare Ventricular tachyarrhythmia Heart failure

33 Pharmacist Clinical Points Confirm patient is receiving antibacterial for CDI Do not co-administer in the same line with other drugs May administer via central or peripheral line Only single dose therapy 65 Technician Tips Must dilute prior to administration Do not shake vial Dilute with 0.9% sodium chloride or Detrose 5% in Water to final concentration of 1 mg/ml to 10 mg/ml May store 16 hours at room temp or 24 hours refrigerated

34 Conclusions Much fewer number of drugs approved in 2016 Majority of those approved were orphan, fast track agents Not much impact on compounding business Critical to understand these new agents 67 References 1. United States Food and Drug Administration. Novel Drug Approvals Accessed January 8, United States Food and Drug Administration. Novel Drugs Summary Accessed March 3, United States Food and Drug Administration. FDA approves Adlyxin to treat type 2 diabetes. Accessed March 3, Adlyxin [package insert]. Bridgewater NJ: Sanofi-Aventis LLC. July Facts and Comparisons. [database online] Indianapolis, IN: Clinical Drug Information. LLC; Accessed January 15, Rosenstock J, Raccah D, Koranyi L et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin. Diabetes Care. 2013;36(10): Pfeffer MA, Claggett B, Diaz R et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373(23): McCaughan GW. New therapies against HCV: Expected risks and challenges associated with their use in the liver transplant setting. J Hepatol. 2012;57(6): AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. Accessed March 1, United States Food and Drug Administration. FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4. Accessed March 4, Zepatier [package insert]. Whitehouse Station NJ: Merck & Co., Inc. February Rockstroh JK, Nelson M, Katlama C et al. Efficacy and safety of gazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV. 2015;2(8):e319-e

35 References 13. Buti M, Gordon SC, Zuckerman E et al. Grazoprevir, elbasvir, and ribavirin for chronic hepatitis C virus genotype 1 infection after failure of pegylated interferon and ribavirin with an earlier-generation protease inhibitor: Final 24-Week results from C-SALVAGE. Clin Infect Dis. 2016;62(1): Roth D, Nelson DR, Bruchfeld A et al. Grazoprevir plus elbasvir in treatment-naive and treatmentexperienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C- SURFER study): a combination phase 3 study. Lancet. 2015;386(10003): United States Food and Drug Administration. FDA approves Epclusa for treatment of chronic Hepatitis C virus infection. Accessed March 5, Epclusa [package insert]. Foster City CA: Gilead Sciences, Inc. February Younossi ZM, Stepanova M, Feld J. et al. Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: results from ASTRAL-1 placebo-controlled trial. J Hepatol. 2016;65(1): Younossi ZM, Stepanova M, Sulkowski M et al. Ribavirin-free regimen with sofosbuvir and velpatasvir is associated with high efficacy and improvement of patient-reported outcomes in patients with genotypes 2 and 3 chronic hepatitis C: Results from Astral-2 and -3 clinical trials. Clin Infect Dis.2016;63(8): Younoss ZM, Stepanova M, Charlton M et al. Patient-reported outcomes with sofosbuvir and velpatasvir with or without ribavirin for hepatitis C virus-related decompensated cirrhosis: an exploratory analysis from the randomised, open-label ASTRAL-4 phase 3 trial. Lancet Gastroenterol Hepatol. 2016;1(100031): References 20. United States Food and Drug Administration. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. Accessed March 6, Exondys 51 [package insert]. Cambridge MA: Sarepta Therapeutics Inc. September Eteplirsen (Exondys 51) for duchenne muscular dystrophy. Med Lett Drugs Ther Nov 7;58(1507): United States Food and Drug Administration. FDA approves Merck s ZINPLAVA (bezlotoxumab) to reduce recurrence of Clostridium difficile infection (CDI) in adult patients receiving antibacterial drug treatment for CDI who are at high risk of CDI recurrence. Accessed March 29, Zinplava [package insert]. Whitehouse Station NJ: Merck and Company. October

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37 New Drugs of 2016 Table 1- New drugs of 2016, listed in order of approval date 1 Generic Name Brand Name Approval Date Indication Elbasvir (ELB as vir) and Zepatier (ZEP-ah-teer) Chronic hepatitis C (HCV) genotypes 1 and 4 infection Grazoprevir (graz OH pre vir) Brivaracetam Briviact Partial onset seizures (BRIV a RA se tam) Obiltoxaximab Anthim Inhalational anthrax (oh-bil-tox-ax-i-mab) Ixekizumab Taltz Moderate to severe plaque psoriasis (IX ee KIZ ue mab) Reslizumab Cinqair Severe asthma (res LIZ ue mab) Defibrotide sodium (de FYE broe tide) Defitelio Hepatic veno-occlusive disease following stem cell transplant Venetoclax (ven ET oh klax) Venclexta Chronic lymphocytic leukemia in patients with a specific chromosomal abnormality Pimavanserin (PIM a VAN ser in) Nuplazid Treatment of hallucinations and delusions from psychosis in Parkinson s disease Tecentriq Urothelial type bladder cancer Atezolizumab (A te zoe LIZ ue mab) Daclizumab Zinbryta Multiple sclerosis (dah KLIH zyoo mab) Obeticholic acid Ocaliva Rare chronic liver disease (oh BET i KOE lik AS id) Fluciclovine F 18 Axumin Diagnostic imaging agent for recurrent prostate cancer detection Gallium Ga 68 dotatate NETSPOT Diagnostic imaging agent for rare (GAL-ee-um Ga 68 DOE-ta-tate) neuroendocrine tumors Sofosbuvir (soe FOS bue vir) Epclusa Treatment of all 6 major forms of and hepatitis C virus Velpatasvir (vel PAT as vir) Lifitegrast (LIF e TEG rast) Lixisenatide (LIX i SEN a tide) Eteplirsen (e TEP lir sen) Olaratumab (OH lar AT ue mab) Bezlotoxumab (BEZ loe TOX ue mab) Crisaborole (KRIS a BOR ole) Rucaparib (roo KAP a rib) Nusinersen (NUE si NER sen) Xiidra Treat signs and symptoms of dry eye Adlyxin Diabetes type 2 Exondys Duchenne muscular dystrophy Lartruvo Soft tissue sarcoma Zinplava Reduce the recurrence of Clostridium difficile infection in adults Eucrisa Atopic dermatitis in patients two years of age or older Rubraca Ovarian cancer Spinraza Spinal muscular atrophy References: 1. United States Food and Drug Administration. Novel Drug Approvals Accessed January 8, 2017.