Page 9
Andexanet could possibly be used as an
antidote for all of the factor Xa inhibitors in
addition to the low molecular-weight heparins
and fondaparinux.
10
Initial costs have been
estimated at $20,000 per bleed for the
IV infusion.
Aripazine is another antidote in the pipeline. It
is a small synthetic molecule that binds to all
DOACs, as well as injectable unfractionated
heparin, low molecular weight heparins and
fondaparinux. This reversal agent is currently
undergoing Phase II trials as a nonspecific
reversal agent. It has the potential to be an
antidote for the same targets as idarucizumab
and andexanet alpha in addition to reversing
unfractionated heparin.
4
The accompanying
table compares the already approved
idarucizumab with the two products in
the pipeline.
Betrixaban is one of the last factor Xa
inhibitors remaining in the pipeline. It is
currently in a Phase III trial evaluating
the superiority of extended-duration
anticoagulation with oral betrixaban (for up
to 35 days in hospital and post-discharge)
compared with injectable enoxaparin (for
10 days) for venous thromboembolism
prevention in acute medically ill patients.
The advantages of betrixaban include use in
patients that have severe renal impairment
(excluding dialysis patients), lack of CYP3A4
metabolism (which reduces the risk of
drug-drug interactions) and the potential
reversibility with andexanet alfa.
12
If approved, betrixaban could be the
first anticoagulant for both hospital and
post-discharge venous thromboembolism
prophylaxis in the acute medically ill and the
standard of care for this large market of more
than 30 million patients worldwide.
12
DOACs have decreased the patient and
clinical burden associated with treating
thromboembolism. And while they still have
some limitations, it is important to keep in
mind what is in the pipeline when reviewing
this class of medications for a preferred drug
list. Many of the existing limitations could be
resolved with the approval of these agents.
That could change how payers evaluate this
class of drugs when developing a preferred
drug list.
As more information becomes
available, healthcare programs
should start exploring how to
add these thromboembolism
therapies for a more cost-effective
approach to improving their
affected members’ health.
References
1. John W. Eikelboom and Jeffrey I. Weitz.
Update
on Antithrombotic Therapy: New Anticoagulants
.
Circulation. 2010; 121:1523-1532. Available at
2. Mekaj YH; Mekaj AY; Duci SB; Miftari EI.
New Oral
Anticoagulants: Their Advantages and Disadvantages
Compared With Vitamin K Antagonists in the Prevention
and Treatment of Patients With Thromboembolic
Events
. Therapeutics and Clinical Risk Management.
Volume 2015:11pg 967–977.
3. Barnes GD; Ageno W; Ansell J; Kaatz S, for the
Subcommittee on the Control of Anticoagulation.
Recommendation on the nomenclature for oral
anticoagulants: communication from the SSC
of the ISTH
. J Thromb Haemost 2015; 13: 1154–6.
4. Alsayegh LG.
Novel Oral Anticoagulants for Stroke
Prophylaxis and Venous Thromboembolism
Prevention and Treatment
. J Patient-Centered Res
Rev. 2015; 2:139–146.
5. Levy JH; Spyropoulos AC; Samama CM;
Douketis J.
Direct Oral Anticoagulants: New Drugs
and New Concepts
. J Am Coll Cardiol Intv.
2014;7(12):1333-1351.
6. Joseph Biskupiak, PhD, MBA; Sameer R. Ghate,
PhD, MSPH; Tianze Jiao, BS; and Diana Brixner, PhD,
RPh.
Cost Implications of Formulary Decisions
on Oral Anticoagulants in Nonvalvular Atrial
Fibrillation
. Journal of Managed Care Pharmacy.
November/December 2013 Vol. 19, No. 9.
7. Praxbind Package Insert. Boehringer Ingelheim
Pharmaceuticals, Inc. Ridgefield, CT. 10.2015.
8. Boehringer Ingelheim Praxbind Press Release.
Available at
9. Pollack C. V. et al.
Idarucizumab for dabigatran reversal
.
NEJM. 2015 June 22 (Epub ahead of print). Available at
10.Clinical Development Andexanet alfa: FXa Inhibitor
Antidote. Portola Pharmaceuticals. Available at
11. Deborah M. Siegal, MD; John T. Curnutte, MD, PhD;
Stuart J. Connolly, MD; et al.
Andexanet Alfa for the
Reversal of Factor Xa Inhibitor Activity
. N Engl J Med
2015; 373:2413-2424.
12. Clinical Development Betrixaban: FXa Inhibitor. Portola
Pharmaceuticals. Available at
Antidote
Target
Structure
Route Storage
Idarucizumab
(already approved)
(Praxbind)
Oral DTI (Pradaxa)
Humanized
monoclonal
antibody
fragment
IV
Refrigerated
Andexanet alfa
(PRT064445 or
PRT4445)
Oral FXa inhibitors (Xarelto, Eliquis,
Savaysa, betrixaban); injectable LMWH
(enoxaparin) and fondaparinux
Modified
recombinant
FXa protein
IV
Refrigerated
Aripazine
(PER977)
Oral FXa inhibitors and DTI (Pradaxa,
Xarelto, Eliquis, Savaysa, betrixaban,
Pradaxa); injectable UFH, LMWH and
fondaparinux
Synthetic small
molecule
IV
Room
temperature
DTI = direct thrombin inhibitor; FXa = factor Xa; IV = intravenous; LMWH = low-molecular-weight heparin;
UFH = unfractionated heparin
