Transcript zinbryta
Zinbryta™ - daclizumab Manufacturer: Biogen, Inc. FDA Approval Date: May 27, 2016 Jenna W. Bartlett, PharmD Candidate Zinbryta™ - daclizumab Objectives • At the end of this presentation participants will be able to: 1. Appropriately recommend Zinbryta™ - (daclizumab) 2. Effectively educate patients on the purpose, proper use and potential adverse effects of Zinbryta™ (daclizumab) Zinbryta™ - daclizumab Clinical Application • Indications: • Treatment of relapsing forms of multiple sclerosis (MS), generally in patients that have had an inadequate response to ≥2 drugs indicated for the treatment of MS • Place in therapy: • Another option for 3rd line (or later) treatment of relapsing MS with the advantage of being a once-monthly selfinjection Zinbryta [package insert]. Zinbryta™ - daclizumab Clinical Application • Contraindications: • Preexisting hepatic disease or hepatic impairment, including ALT or AST ≥2x ULN • History or autoimmune hepatitis or other autoimmune condition involving the liver • Black Box warnings: • Hepatotoxicity including autoimmune hepatitis • Other immune-mediated disorders • Precautions: • Acute hypersensitivity • Increased risk of infections • Depression-related events Zinbryta [package insert]. Zinbryta™ - daclizumab Clinical Application • Pregnancy: • No human data available • Fetal death and reduced growth seen in monkeys at maternal exposures >30 times than that expected clinically • Lactation: • No data available Zinbryta [package insert]. Zinbryta™ - daclizumab Drug Facts • Pharmacology: • Humanized monoclonal antibody that binds to CD25, a subunit of the IL-2 receptor • Involves modulation of IL-2 mediated activation of lymphocytes • The exact mechanism for therapeutic effect is unknown Zinbryta [package insert]. Zinbryta™ - daclizumab Drug Facts • Pharmacokinetics: A Steady state: 4 months D Vd = 6.34L M Catabolism to peptides and amino acids E T1/2 = 21 days Zinbryta [package insert]. Zinbryta™ - daclizumab Drug Interactions • Drug Interactions – Object Drugs: • Live vaccines: enhanced toxicities and diminished efficacy • Inactivated vaccines: diminished efficacy • Immunosuppressants: enhanced toxicities and immunosuppressive effect UpToDate Accessed 09/07/16 Zinbryta [package insert]. Zinbryta™ - daclizumab Drug Interactions • Drug Interactions – Precipitant Drugs: • Immunosuppressants may enhance toxicities of Zinbryta • Hepatotoxic drugs may increase risk of hepatotoxicity UpToDate Accessed 09/07/16 Zinbryta [package insert]. Zinbryta™ - daclizumab Adverse Effects • Common Adverse Effects: (daclizumab%)[placebo%] • Upper respiratory tract infection (9) [7] • Rash (7) [3] • Pharyngitis (6) [4] • Serious Adverse Effects: (daclizumab%)[placebo%] • Depression (7) [3] • Increased ALT (5) [2] • Increased AST (3) [<1] Zinbryta [package insert]. Zinbryta™ - daclizumab Monitoring Parameters • Toxicity Monitoring: • AST • ALT • Total bilirubin • Monitor at baseline, then monthly up to 6 months after the last dose Zinbryta [package insert]. Zinbryta™ - daclizumab Prescription Information • Dosing: 150 mg SubQ monthly • Remove prefilled syringe from refrigerator 30 min prior to injection to allow drug to warm • Do not use if it is cloudy or has visible particles • Inject into the thigh, abdomen, or back of the upper arm • Cost: $8200/month • Source – UpToDate 08/26/2016 Zinbryta [package insert]. Zinbryta™ - daclizumab Literature Review • Purpose: • To compare the efficacy of daclizumab versus interferon beta-1a in the treatment of relapsingremitting MS • Design: • Randomized, double-blind, phase 3 study • Group 1: daclizumab 150 mg SubQ every 4 weeks + placebo IM once weekly • Group 2: interferon beta-1a 30 µg IM once weekly + placebo SubQ once monthly Kappos L, et al. N Engl J Med. 2015;373:1418-28 Zinbryta™ - daclizumab Literature Review • Inclusion Criteria: • Confirmed diagnosis of relapsing-remitting MS • Age 18-55 years • Cranial MRI with lesions consistent with a diagnosis of MS • Expanded Disability Status Scale score of 0-5 • History of clinical relapses within the previous year Kappos L, et al. N Engl J Med. 2015;373:1418-28 Zinbryta™ - daclizumab Literature Review • Patient Characteristics: • N=1841 patients • Mean 36 years old • 68% female, 90% white • 41% previous disease-modifying therapy • 34% previous interferon beta therapy • 4 years since diagnosis • 1.6 relapses in previous year Kappos L, et al. N Engl J Med. 2015;373:1418-28 Zinbryta™ - daclizumab Literature Review • Efficacy Results: End Point Adjusted annualized relapse rate New or enlarged lesions Disability progression Daclizumab Interferon beta-1a P value 0.22 0.39 <0.001 4.3 9.4 <0.001 16 20 0.16 Kappos L, et al. N Engl J Med. 2015;373:1418-28 Zinbryta™ - daclizumab Literature Review • Safety Results: Daclizumab (%) Interferon beta-1a (%) Any event (excluding relapse) 90 89 Serious ADE (excluding relapse) 15 10 Infection 65 57 Cutaneous event 37 19 Hepatic event 16 14 Influenza-like illness 10 38 Event Kappos L, et al. N Engl J Med. 2015;373:1418-28 Zinbryta™ - daclizumab Literature Review • Conclusions: • Daclizumab has superior efficacy vs interferon beta-1a with respect to relapse and lesion activity • No significant difference between treatments with respect to disability progression • Daclizumab has increased ADE vs interferon beta-1a, so the net clinical benefit should be carefully considered Kappos L, et al. N Engl J Med. 2015;373:1418-28. Zinbryta™ - daclizumab Summary • Zinbryta™, daclizumab, is indicated for relapsing MS, as 3rd line (or later) treatment • Contraindicated in preexisting hepatic disease or impairment • Because of hepatotoxicity risk, monitor AST/ALT and bilirubin monthly up to 6 months after last dose (REMS program) • Dosing is 150mg SubQ once monthly Zinbryta™ - daclizumab References 1. https://www.zinbryta.com/content/dam/commercial/ multiple-sclerosis/zinbryta/pat/en_us/pdfs/zinbrytaprescribing-information.pdf) 2. Zinbryta [package insert]. Cambridge, MA: Biogen Inc; 2016. 3. Daclizumab. UpToDate. Accessed 09/07/2016. 4. Kappos L, et al. Daclizumab HYP versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2015;373:1418-28. 5. Gold R, et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT). Lancet 2013; 381: 2167-75.