1. Praxbind® - Idarucizumab
Manufacturer: Boehringer Ingelheim Pharmaceuticals, Inc.
FDA Approval Date: 10/16/2015

2. Praxbind® - Idarucizumab Objectives
At the end of this presentation participants will be able to:
Appropriately recommend Praxbind® - (idarucizumab)
Effectively educate patients on the purpose, proper use and potential adverse effects of Praxbind® - (idarucizumab)

3. Praxbind® - Idarucizumab Clinical Application
Indications:
Patient’s treated with Pradaxa (dabigatran) that require anticoagulation reversal in cases of:
Emergency Surgery or Urgent Procedure
Life Threatening Bleeding
Place in therapy:
First in market reversal agent for new oral anticoagulation dabigatran
Praxbind ® [package insert].

4. Praxbind® - Idarucizumab Clinical Application
Contraindications:
None
Warnings and Precautions:
Thromboembolic risk
Re-elevation of coagulation parameters
Hypersensitivity
Fructose intolerance
Praxbind ® [package insert].

5. Praxbind® - Idarucizumab Clinical Application
Pregnancy:
No Data
Lactation:
Praxbind ® [package insert].

6. Praxbind® - Idarucizumab Drug Facts
Pharmacology:
Humanized monoclonal antibody fragment (Fab) that binds to dabigatran and its acylglucuronide metabolites with an affinity higher than that of thrombin
This specific binding neutralizes the anticoagulation effect of dabigatran
Antibody is lock/key with dabigatran
Praxbind ® [package insert].

7. Praxbind® - Idarucizumab Drug Facts
Pharmacokinetics:
A – t ½ 47 minutes, terminal t ½ 10.3h
D – Multiphasic with limited extravascular distribution. VoD 8.9 L
M – Biodegradation of the antibody to small peptides
E – ~30% eliminated in the urine, the rest is eliminated via degradation
Praxbind ® [package insert].

8. Praxbind® - Idarucizumab Drug Interactions
No remarkable drug interactions determined via a theoretical mechanism, in vitro assessment, or in animal models
Praxbind ® [package insert].

9. Praxbind® - Idarucizumab Adverse Effects
Healthy volunteers
Headache 5%
REVERSE-AD trial
Hypokalemia: 7%
Delirium: 7%
Constipation 7%
Pyrexia: 6%
Pneumonia: 6%
Serious Adverse Effects:
5 of 123 patients in the REVERSE-AD trial had a thrombotic event
Praxbind ® [package insert].

10. Praxbind® - Idarucizumab Monitoring Parameters
Efficacy Monitoring:
Baseline aPTT, re-evaluation of aPTT at 12 and 24 hours
Monitor for signs and symptoms of bleed
Toxicity Monitoring:
Monitor for hypersensitivity or immunogenic reactions
Praxbind ® [package insert].

11. Praxbind® - Idarucizumab Prescription Information
Dosing: 5 g infusion: provided as two 2.5g/50 mL vials. There is limited data to support a second 5 g infusion
Cost: – NEJM Journal Watch. November 5, 2015
2.5g/50 mL vial ~$3500
Cost per treatment: $7000
Praxbind ® [package insert].

12. Praxbind® - Idarucizumab RE-VERSE AD Trial
Pollack CV, et al. N Engl J Med Aug 6;373(6):

13. Praxbind® - Idarucizumab RE-VERSE AD Trial
Purpose: Examine efficacy and safety of idarucizumab for dabigatran reversal
Study Design:
Multicenter, prospective cohort study
Interim analysis, data on 90 of 300 pts
Each patient received two 2.5 g infusions 15 minutes apart
Pollack CV, et al. N Engl J Med Aug 6;373(6):

14. Praxbind® - Idarucizumab REVERSE-AD Trial
Inclusion:
18 y/o, and on dabigatran
Group A: Life-threatening bleed
Group B: Urgent surgery or procedure required
Pollack CV, et al. N Engl J Med Aug 6;373(6):

15. Praxbind® - Idarucizumab Endpoints
Primary:
Maximum percentage reversal
Secondary:
Proportion with normalization of dilute thrombin time
Proportion with normalization of ecarin clotting time
Reduction in concentration of unbound dabigatran
Safety:
All adverse events captured
Pollack CV, et al. N Engl J Med Aug 6;373(6):

16. Praxbind® - Idarucizumab Patient Characteristics
Baseline Characteristics
Age 77
Race
87%
CrCL
62 mL/min
Atrial Fibrillation
96%
Last dose of dabigatran
15 hr
Elevated Dilute thrombin time at baseline
76%
Elevated ecarin clotting time at baseline
90%
Pollack CV, et al. N Engl J Med Aug 6;373(6):

17. Praxbind® - Idarucizumab Results
22 patients had dilute thrombin times that were within normal limits and 9 of those patients had normal clotting times excluding these 22 pts from analysis (Group A - 40 patients and Group B patients).
81 of 90 were assessed with ecarin-clotting time test (Group A - 47 patients and Group B patients).
All patients received idarucizumab regardless of their inclusion in the efficacy analysis
Pollack CV, et al. N Engl J Med Aug 6;373(6):

18. Praxbind® - Idarucizumab Results
Primary:
Maximum percentage reversal in Groups A and B was 100%
Reversal was evident on first sample taken after infusion
Secondary:
Normalization of clotting time
Dilute Thrombin Time
Ecarin Clotting Time
Group A
98%
89%
Group B
93%
88%
-Of the 22 patients with normal dilute thrombin time and ecarin clotting time, renal function was better than those included in analysis (67 mL/min versus 48 mL/min)
-Baseline unbound dabigatran concentration was 84 ng/mL in Group A and 76 ng/mL in Group B. Unbound dabigatran was less than 20 ng/mL in all patients but one after reversal
Pollack CV, et al. N Engl J Med Aug 6;373(6):

19. Praxbind® - Idarucizumab Safety
Safety Outcomes
Death
18/90 (20%)
Serious Adverse Event
21/90 (23.3%) MI
1/90 (1%)
Stroke
DVT/PE
3/90 (3.3%)
Pollack CV, et al. N Engl J Med Aug 6;373(6):

20. Praxbind® - Idarucizumab Conclusions
Praxbind® is effective in reversing anticoagulation of dabigatran
Minimal adverse event profile
Small population using dabigatran will limit the impact of this medication
Pollack CV, et al. N Engl J Med Aug 6;373(6):

21. Praxbind® - Idarucizumab Summary
Praxbind®, idarucizumab, is a humanized monoclonal antibody that reverses the anticoagulation effect of dabigatran
Idarucizumab is indicated for patients treated with dabigatran that have a life-threatening or uncontrolled bleed, or require an emergency or urgent procedure
Idarucizumab is 5g administered as two 2.5g infusions
There is a risk of rebound anticoagulation hours after administration
Hypersensitivity reactions are possible despite humanization of the antibody

22. Praxbind® - Idarucizumab References
Accessed 11/20/2015.
Praxbind package insert. Boehringer Ingelheim Pharmaceuticals, Inc. Oct 2015.
Boehringer Ingelheim Pharmaceuticals Inc. Praxbind ® approval announcement. provedDrugs/ucm htm. Accessed 11/20/15.
Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med Aug 6;373(6):