Praxbind® - IdarucizumabManufacturer: Boehringer Ingelheim

Pharmaceuticals, Inc.

FDA Approval Date: 10/16/2015

Praxbind® - Idarucizumab

Objectives

• At the end of this presentation participants will be able to:1. Appropriately recommend Praxbind® -

(idarucizumab)

2. Effectively educate patients on the purpose, proper use and potential adverse effects of Praxbind® - (idarucizumab)

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].

Praxbind® - Idarucizumab

Clinical Application

• Contraindications:• None

• Warnings and Precautions:• Thromboembolic risk

• Re-elevation of coagulation parameters

• Hypersensitivity

• Fructose intolerance

Praxbind ® [package insert].

Praxbind® - Idarucizumab

Clinical Application

• Pregnancy:• No Data

• Lactation:• No Data

Praxbind ® [package insert].

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].

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].

Praxbind® - Idarucizumab

Drug Interactions

• No remarkable drug interactions determined via a theoretical mechanism, in vitro assessment, or in animal models

Praxbind ® [package insert].

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].

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].

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].

PRAXBIND® - IDARUCIZUMAB

RE-VERSE AD TRIAL

Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.

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. 2015 Aug 6;373(6):511-20.

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. 2015 Aug 6;373(6):511-20.

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. 2015 Aug 6;373(6):511-20.

Praxbind® - Idarucizumab

Patient Characteristics

Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.

Baseline CharacteristicsAge 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%

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 - 28 patients).

• 81 of 90 were assessed with ecarin-clotting time test (Group A - 47 patients and Group B - 34 patients).

• All patients received idarucizumab regardless of their inclusion in the efficacy analysis

Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.

Praxbind® - Idarucizumab

Results

• Primary:

• Maximum percentage reversal in Groups A and B was 100%

• Reversal was evident on first sample taken after infusion

• Secondary:

Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.

Normalization of clotting time  Dilute Thrombin

TimeEcarin Clotting

TimeGroup A 98% 89%Group B 93% 88%

Praxbind® - Idarucizumab

Safety

Pollack CV, et al. N Engl J Med. 2015 Aug 6;373(6):511-20.

Safety Outcomes

Death 18/90 (20%)

Serious Adverse Event 21/90 (23.3%)

MI 1/90 (1%)

Stroke 1/90 (1%)

DVT/PE 3/90 (3.3%)

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. 2015 Aug 6;373(6):511-20.

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 12-24 hours after administration

• Hypersensitivity reactions are possible despite humanization of the antibody

Praxbind® - Idarucizumab

References

1. http://www.praxbind.com/ Accessed 11/20/2015.

2. Praxbind package insert. Boehringer Ingelheim Pharmaceuticals, Inc. Oct 2015.

3. Boehringer Ingelheim Pharmaceuticals Inc. Praxbind ® approval announcement. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm467396.htm. Accessed 11/20/15.

4. Pollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med. 2015 Aug 6;373(6):511-20.