6/29/2018 #FSHP2018 #FSHP2018 #FSHP2018 #FSHP2018 #FSHP2018

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1 Disclosure Statement New Drugs I have no conflicts of interest to disclose Steven Walden, PharmD, MPH WellCare Health Plans Manager, Clinical Implementations Learning Objectives At the completion of this program, participants will be able to: Provide an overview of the following new drugs that were approved in 2017: Ocrevvus (ocrelizumab) Vosevi (Sofosbuvir, velpatasvir, and voxilaprevir) Shingrix (Zoster Vaccine Recombinant, Adjuvanted) KebRab (Rabies Immune Globulin (Human) List the indications State the dosage forms and delivery systems List any special preparation and handling Discuss the disease states OCREVUS is indicated for the treatment of adult patients with relapsing or primary progressive forms of multiple sclerosis. (March 2017) Multiple Sclerosis (MS) What is it: Disabling disease of the central nervous system Disrupts the flow of information within the brain, and between the brain and body What causes it: Cause is unknown Believe the disease is triggered by an unidentified environmental factor in a person who is genetically predisposed to respond Multiple Sclerosis (MS) Multiple sclerosis (MS) involves an immune-mediated process in which an abnormal response of the body s immune system is directed against the central nervous system (CNS) 1

2 MS Epidemiology Affects more than 2.3 million people worldwide In the US, about 400,000 Mostly occurs between age 20 and 50 Two to three more common in women More common in areas farthest from the equator Genetic factors play a significant role in occurrence MS Disease Categories Clinically Isolated Syndrome (CIS) first episode Relapsing-remitting MS (RRMS) most common, defined attacks of increasing neurologic symptoms (Relapses) Secondary progressive MS (SPMS) transition to SPMS. Worsening of neurologic function Primary progressive MS (PPMS) - worsening neurologic function from the onset of symptoms, without early relapses or remissions MS Symptoms - Diagnosis Fatigue Walking difficulties Blurred vision Dizziness and vertigo Bladder dysfunction Constipation Chronic pain MRI and CSF analysis Damage in two separate areas of the CNS Damage occurred at different point in time OCREVUS is a recombinant humanized monoclonal antibody directed against CD20- expressing B-cells OCREVUS injection is a preservative-free, sterile, clear or slightly opalescent, and colorless to pale brown solution containing 300 mg/10 ml (30 mg/ml) single-dose vial Recommended Dosage and Administration Initial dose of 300mg IV infusion Two weeks later administer a second 300mg dose by IV infusion Subsequent doses of 600mg IV infusion every 6 months Observe the patient for 1 hour after infusion Assessments Prior to First Dose Hepatitis B Virus screening Ocrevus is contraindicated in patients with active HBV Vaccinations: no live vaccines during treatment until B-cell repletion. 2

3 Preparation Before Every Infusion Assess if there is an active infection. Do not administer Premedication: Methylprednisolone 100mg IV 30 min prior to Ocrevus infusion. Reduces infusion reactions Antihistamine minutes prior to Ocrevus infusion. Reduces infusion reactions Acetaminophen may also be given prior to infusion Solutions of OCREVUS for intravenous infusion are prepared by dilution of the drug product into an infusion bag containing 0.9% Sodium Chloride Injection, to a final drug concentration of approximately 1.2 mg/ml Preparation and Storage of the Dilute Solution for Infusion Preparation: Mix with 0.9% Sodium Chloride Use the prepared infusion solution immediately If not used immediately, store up to 24 hours in the refrigerator at 36 F 46 F and 8 hours at room temperature up to 77 F, which includes infusion time. WARNINGS AND PRECAUTIONS Infusion Reactions mild to severe Infections URT, LRT, skin Malignancies Breast cancer Place in therapy First drug for Primary progressive MS (PPMS) Granted Breakthrough Therapy Designation for Primary- Progressive MS by FDA Ocrevus (ocrelizumab) was more effective than Rebif(interferon beta-1a) at preventing relapsing multiple sclerosis activity, according to an analysis that covered two Phase 3 clinical trials $65,000 per year (lower than other MS drugs) 3

4 Hepatitis C Virus (HCV) VOSEVI is indicated for the treatment of adult patients with chronic hepatitis C virus infection without cirrhosis or with compensated cirrhosis genotype 1, 2, 3, 4, 5 or 6. (July 2017) What is it: Liver infection caused by HCV, a blood-borne virus Results in a long-term, chronic infection in 70-85% of cases What causes it: Most people are infected by sharing needles to inject drugs HCV Genotypes There are 6 genotypes with subtypes Genotype 1 75% of infections (subtype 1a or 1b) Genotype 2 or 3 15% -20% of infections Genotype 4, 5, 6 less than 5% HCV Epidemiology/Risk An estimated 3.5 million people in the US have chronic Hep C Increased Risk Current/former injection drug users (even 1 occurrence) Receive clotting factor drugs before 1987 Receive blood transfusions or organ transplants before 1992 Chronic hemodialysis Needle sticks in healthcare workers Children born to HCV-positive mothers HCV Signs and Symptoms Fever Fatigue Clay-colored stools Abdominal pain N/V Jaundice Joint pain HCV Treatment Over 90% of HCV infected persons can be cured with 8-12 weeks of oral therapy (sustained virologic response (SVR) defined as the absence of detectable virus 12 weeks after completion of treatment) Based on genotype, prior treatment, with or without liver cirrhosis Combination therapy used to reduce resistance development 4

5 Direct Acting Antivirals (DAA) Vosevi Fixed-dose combination of Sofosbuvir, Velpatasvir, Voxilaprevir Indicated for the treatment of adult patients with chronic hepatitis C virus infection without cirrhosis or with compensated cirrhosis genotype 1, 2, 3, 4, 5 or 6 Vosevi Vosevi - Dosage One tablet (SOF-400mg, VEL-100mg, VOX-100mg) once daily with food Not recommended in patients with moderate or severe hepatic impairment (Child-Pugh B or C) Not to be administered with rifampin Vosevi Boxed Warning Vosevi Warnings & Precautions Serious symptomatic bradycardia When coadministered with Amiodarone Risk of Reduced Therapeutic Effect Due to concomitant Use of VOSEVI with Inducers of P-gp and/or moderate to potent inducers of CYP St. John s wort, carbamazepine 5

6 Vosevi Adverse Reactions Rash in <2% Depression in <1% Vosevi Clinical Trial POLARIS-4 Trial Vosevi vs. SOF/VEL for 12 weeks Genotype 1a and 3 Numerically higher SVR12 rates Genotype 1b and 2 Comparable SVR12 rates Genotypes 4, 5, 6 no comparison data available Vosevi Place in Therapy Additional benefit over Sof/Vel for genotypes 1a and 3 Only product with three DDA ingredients Cost: $890 per tablet or $74,760 for a 12 week course of therapy Cost of other therapies SOF/VEL - $ 74,760 Sovaldi - $84,000 Harvoni - $94,500 is a vaccine indicated for the prevention of herpes zoster (shingles) in adults aged 50 years and older. (October 2017) Shingles (Herpes zoster) What is it: A painful rash that develops on one side of the face or body Blisters that scab over in 7-10 days Rash clears within 2 to 4 weeks What causes it: Varicella zoster virus (VZV) Same virus that causes chickenpox Virus stays dormant in body Not sure what causes reactivation to cause shingles Shingles - Symptoms Rash occurs in a single stripe on the body Fever Headache Chills Upset stomach 6

7 Shingles - Epidemiology One in three people in the US will develop shingles About 1 million cases each year Most people have only one episode Anyone who has had chickenpox may develop shingles Can not be transmitted to another person, may cause chickenpox if that person has not had chickenpox (blister-phase) Shingles Complications Postherpetic neuralgia (PHN) - 10 to 13% Severe pain in same location Resolves over a few months Increases with age May cause vision loss if affects eye (Zoster Vaccine Recombinant, Adjuvanted) is a sterile suspension for intramuscular injection containing recombinant varicella zoster virus surface glycoprotein E (ge) antigen component. The suspension must be reconstituted with the accompanying vial of AS01 B adjuvant suspension component Recommended Dosage and Administration IM injection only Two doses (0.5ml each=1 vial), second dose administered between 2 and 6 months after initial dose Administer immediately or store refrigerated and use within 6 hours. Single dose vial Reconstitution Directions Who Should Receive Singrix? Health adult 50 years Had shingles Received Zostavax (wait at least 8 weeks) Had chickenpox or not sure No maximum age Not studied in individuals younger than 18 years 7

8 Adverse Effects Local Reactions Pain Redness Swelling General Adverse Events Myalgia Fatigue Headache Shivering, fever Efficacy Efficacy on Overall Incidence of PHN Overall ( 70) 88.8% % % Place in therapy CDC recommends Shingrix as preferred over Zostavax Shingrix is not effective in preventing Chickenpox Varicella vaccine is given to children between 12 and 15 months with a booster at 4 to 6 years to prevent chickenpox KEDRAB is a human rabies immunoglobulin indicated for passive, transient postexposure prophylaxis of rabies infection. (August 2017) Human Rabies What is it: Rabies is a preventable viral disease of mammals most often transmitted through the bite of a rabid animal The rabies virus infects the central nervous system, ultimately causing disease in the brain and death It may take 2 weeks to months for symptoms to appear Initiate treatment immediately after exposure (bite) What causes it: A zoonotic disease caused by RNA viruses in the family of Rhabdoviridae, genus Lyssavirus Most common animals; raccoon (East), skunk (Midwest, CA), fox (Southwest) Human Rabies - Symptoms Flu-like; weakness, fever, HA Itching at bite site Confusion, anxiety, agitation Delirium, hallucinations, insomnia Acute phase ends after 2-10 days Once symptoms appear, almost always fatal 8

9 Human Rabies - Epidemiology Only 1 to 3 cases annually within the US 40,000 people receive post-exposure prophylaxis in US Worldwide 60,000 die annually and 15 million receive post-exposure prophylaxis. Primary animal is dog worldwide Is only transmitted through saliva and brain/nervous system tissue. Petting or handling infected animal is not an exposure Human Rabies - Vaccination Post-exposure should include passive and vaccine KEDRAB KEDRAB is a human rabies immunoglobin (HRIG) It has the potential to attenuate the patient s immune response to rabies vaccine It should be administered concurrently with a full course of rabies vaccine Do not administer repeated doses once vaccine treatment has been started KEDRAB Recommended Dosage and Administration Administer as soon as possible after exposure Administer at time of first vaccine dose For wound infiltration and intramuscular use Single dose of 20IU/kg body weight Infiltrate this dose into and around bite, administer remainder IM at a site distant from vaccination site KEDRAB How Supplied Keep vial in carton until use. Single-use vial containing 2 ml or 10 ml of readyto-use solution with a potency of 150 IU/mL Store in refrigerator (36-46 o ). Do not freeze Can be stored at room temperature for up to one month. Do not return to refrigerator KEDRAB Adverse Effects Injection site pain Headache Muscle pain Upper respiratory tract infection Previous Rabies vaccination If patient received complete previous rabies preexposure or post-exposure prophylaxis, they should only receive a booster rabies vaccine 9

10 KEDRAB Place in Therapy REFERNECES The FDA Advisory Committee stated: the efficacy and safety of KEDRAB do not differ from the other HRIGs Price currently not available. Not being distributed in US yet Price of comparable products: HyperRAB - $3,550 (370% increase in 10 years) Imogam - $3,612 (388% increase in 10 years) Genentech Inc. (2017). Ocrevus (ocrelizumab) Package Insert. Ocrevus (ocrelizumab) Package Insert. South San Francisco, CA. Gilead Sciences, Inc. (2017). Vosevi Package Insert. Vosevi Package Insert. Foster City, CA. GlaxoSmithKline Biologicals. (2017). Shingrix (Zoster Vaccine Recombinate, Adjuvanted) Package Insert. Shingrix (Zoster Vaccine Recombinate, Adjuvanted) Package Insert. Research Triangle Park, NC. Kedrion Bipharma Inc. (2017). Kedrab Rabies Immune Globulin Package Insert. Kedrab Rabies Immune Globulin Package Insert. Fort Lee, NJ. National Multiple Sclerosis Society. (n.d.). MS Society Home page. Retrieved from National Multiple Sclerosis Society: U.S. Department of Health & Human Services. (January, ). Centers for Disease Control and Prevention. Retrieved from Rabies: U.S. Department of Health & Human Services. (2015, May 31). Centers for Disease Control and Prevention. Retrieved from Viral Hepatitis - Hepatitis C: U.S. Department of Health & Human Services. (2018, January 19). Centers for Disease Control. Retrieved from Shingles (Herpes Zoster): World Health Organization. (2018). Rabies. Retrieved from Human rabies: ANY QUESTIONS? New Drugs Steven Walden, PharmD, MPH WellCare Health Plans Manager, Clinical Implementations 10