Download daclizumab

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.