1. Venous
thromboembolism
(VTE)
January 2016
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2. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
Reference: DMKC0148764
First published: 07/01/2016
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3. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
TABLE OF CONTENTS
LIST OF FIGURES
5 EXECUTIVE SUMMARY
6 PRODUCT OVERVIEW
6 Key marketed drugs for venous thromboembolism
6 Bibliography
7 PRODUCT PROFILES
7 Coumadin : Venous thromboembolism
24 Eliquis : Venous thromboembolism
47 Lovenox : Venous thromboembolism
68 Pradaxa : Venous thromboembolism
87 Savaysa : Venous thromboembolism
101 Xarelto : Venous thromboembolism
17 Figure 1: Coumadin for venous thromboembolism – SWOT analysis
18 Figure 2: Datamonitor Healthcare’s drug assessment summary of Coumadin for venous
thromboembolism
19 Figure 3: Datamonitor Healthcare’s drug assessment summary of Coumadin for venous
thromboembolism
41 Figure 4: Eliquis for venous thromboembolism – SWOT analysis
41 Figure 5: Datamonitor Healthcare’s drug assessment summary of Eliquis for venous
thromboembolism
42 Figure 6: Datamonitor Healthcare’s drug assessment summary of Eliquis for venous
thromboembolism
62 Figure 7: Lovenox for venous thromboembolism – SWOT analysis
62 Figure 8: Datamonitor Healthcare’s drug assessment summary of Lovenox for venous
thromboembolism
63 Figure 9: Datamonitor Healthcare’s drug assessment summary of Lovenox for venous
thromboembolism
79 Figure 10: Pradaxa for venous thromboembolism – SWOT analysis
80 Figure 11: Datamonitor Healthcare’s drug assessment summary of Pradaxa for venous
thromboembolism
81 Figure 12: Datamonitor Healthcare’s drug assessment summary of Pradaxa for venous
thromboembolism
95 Figure 13: Savaysa for venous thromboembolism – SWOT analysis
96 Figure 14: Datamonitor Healthcare’s drug assessment summary of Savaysa for venous
thromboembolism
96 Figure 15: Datamonitor Healthcare’s drug assessment summary Savaysa for venous
thromboembolism
111 Figure 16: Xarelto for venous thromboembolism – SWOT analysis
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4. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
LIST OF TABLES
112 Figure 17: Datamonitor Healthcare’s drug assessment summary of Xarelto for venous
thromboembolism
112 Figure 18: Datamonitor Healthcare’s drug assessment summary of Xarelto for venous
thromboembolism
6 Table 1: Key marketed drugs for venous thromboembolism
7 Table 2: Coumadin drug profile
10 Table 3: Coumadin pivotal trial data in venous thromboembolism
25 Table 4: Eliquis drug profile
29 Table 5: Eliquis pivotal trial data in venous thromboembolism
38 Table 6: Eliquis late-phase trial data in venous thromboembolism
40 Table 7: Eliquis ongoing late-phase clinical trials in venous thromboembolism
47 Table 8: Lovenox drug profile
52 Table 9: Lovenox pivotal trial data in venous thromboembolism
59 Table 10: Lovenox late-phase trial data in venous thromboembolism
68 Table 11: Pradaxa drug profile
72 Table 12: Pradaxa pivotal trial data in venous thromboembolism
77 Table 13: Pradaxa late-phase trial data in venous thromboembolism
79 Table 14: Pradaxa ongoing late-phase clinical trials in venous thromboembolism
87 Table 15: Savaysa drug profile
90 Table 16: Savaysa pivotal trial data in venous thromboembolism
93 Table 17: Savaysa late-phase trial data in venous thromboembolism
94 Table 18: Savaysa ongoing late-phase clinical trial in venous thromboembolism
101 Table 19: Xarelto drug profile
105 Table 20: Xarelto pivotal trial data in venous thromboembolism
109 Table 21: Xarelto late-phase trial data in venous thromboembolism
SAM
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5. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
PRODUCT OVERVIEW
Key marketed drugs for venous thromboembolism
Bibliography
Kaken Pharmaceutical (2015) History. Available from: http://www.kaken.co.jp/english/history.html
[Accessed 25 September 2015].
Rhône-Poulenc (1999) Annual Report 1998. Available from:
http://globaldocuments.morningstar.com/documentlibrary/document/b36c36491a70dd7d.msdoc/origi
nal [Accessed 25 September 2015].
Table 1: Key marketed drugs for venous thromboembolism
Brand Molecule Originator
company
Partner Approval date US Approval date EU Approval date
Japan
Coumadin warfarin Endo Products (now
Bristol-Myers
Squibb)
n/a June 1954 n/a n/a
Eliquis apixaban Bristol-Myers
Squibb
Pfizer March 2014 May 2011 February 2015
Lovenox enoxaparin Sanofi Kaken
Pharmaceutical
March 1993 March 1998 January 2008
Pradaxa dabigatran Boehringer
Ingelheim
n/a April 2014 March 2008 September 2015
Savaysa edoxaban Daiichi Sankyo n/a February 2015 June 2015 April 2011
Xarelto rivaroxaban Bayer Johnson & Johnson July 2011 September 2008 September 2015
Source: BioMedTracker, Copyright 2015, reprinted with permission; Kaken Pharmaceutical,
2015; Medtrack, September 2015, Copyright Informa UK; Pharmaprojects ®, 2015; Citeline;
Rhône-Poulenc, 1999
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6. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
Pradaxa : Venous thromboembolism
PRODUCT PROFILE
Analyst Outlook
Pradaxa (dabigatran; Boehringer Ingelheim) is facing strong competition from the current market-
leading novel oral anticoagulants (NOACs) Eliquis (apixaban; Bristol-Myers Squibb/Pfizer) and Xarelto
(rivaroxaban; Bayer/Johnson & Johnson), due to concerns raised by patients and physicians over the
safety of the drug. With the approval of Praxbind (idarucizumab; Boehringer Ingelheim), Pradaxa is
the first NOAC drug to have an antidote on the market. This is likely to increase Pradaxa’s sales by
increasing its adoption among physicians concerned about the lack of an antidote in the NOAC drug
class. However, the first-to-market advantage for Pradaxa’s novel antidote will be short-lived due to
the expected approval of rival antidote andexanet alfa (Portola Pharmaceuticals) for competitor
molecules Eliquis and Xarelto in 2016.
Drug Overview
Pradaxa is an orally available direct thrombin inhibitor (factor IIa inhibitor) indicated for the
treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients who previously
received treatment with a parenteral anticoagulant for 5−10 days. It is also indicated for reducing the
risk of recurrence of DVT and PE in previously treated patients. Pradaxa acts by inhibiting the
conversion of fibrinogen into fibrin during the coagulation cascade, thereby preventing thrombus
development (FDA, 2015a).
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7. Venous thromboembolism Marketed Drugs DMKC0148764 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
Public lawsuits and loss of physician confidence has led to a sales deficit for Pradaxa
Pradaxa experienced a decline in overall sales in 2014 due to its decreasing popularity among patients
and physicians, caused by public lawsuits and numerous adverse events. Pradaxa sales declined by
0.7% in 2014, which is mainly attributed to the loss of physician confidence in the drug’s safety after
numerous cases of gastrointestinal bleeding and intracranial hemorrhage were reported to the US
Food and Drug Administration (FDA) (Boehringer Ingelheim, 2014d). Pradaxa has faced more than
4,000 public lawsuits since 2011, with a settlement of around $650m, which impacted the drug’s
projected earnings in 2014 (Boehringer Ingelheim, 2014c). By presenting data from the Phase III
clinical trial of its novel antidote molecule Praxbind, Boehringer Ingelheim can tackle the negative
publicity garnered by these lawsuits and offer healthcare providers confidence in prescribing the first
reversible NOAC.
Concerns about twice-daily dosing and adverse events is affecting Pradaxa’s
competitiveness in the VTE market
Pradaxa’s twice-daily dosing schedule, along with its higher rates of gastrointestinal intolerability,
bleeding, and myocardial infarctions, is impacting the drug’s competitiveness in the VTE market. These
concerns provide a strategic advantage to some of the other NOAC drugs in the market, which has
increased their adoption among physicians.
Patient compliance is a significant issue in the treatment of VTE, as the impact of discontinuation of
anticoagulation treatment is not always immediately obvious to the patient. NOAC drugs have a
Figure 12: Datamonitor Healthcare’s drug assessment summary of Pradaxa for venous thromboembolism
Source: Datamonitor Healthcare
SAM
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8. Venous thromboembolism Pipeline DMKC0148708 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
TABLE OF CONTENTS
LIST OF FIGURES
LIST OF TABLES
4 EXECUTIVE SUMMARY
5 CLINICAL PIPELINE OVERVIEW
5 Pipeline summary
6 TARGET PRODUCT PROFILE
6 Comparator therapy
16 Bibliography
17 LATE STAGE DRUGS
17 betrixaban : Venous thromboembolism
19 Figure 1: Betrixaban for venous thromboembolism – SWOT analysis
20 Figure 2: Datamonitor Healthcare’s drug assessment summary of betrixaban for venous
thromboembolism
21 Figure 3: Datamonitor Healthcare’s drug assessment summary of betrixaban for venous
thromboembolism
5 Table 1: Phase III pipeline products in development for venous thromboembolism
6 Table 2: Coumadin drug profile
9 Table 3: Coumadin pivotal trial data in venous thromboembolism
17 Table 4: Betrixaban drug profile
19 Table 5: Betrixaban Phase III trial in venous thromboembolism
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9. Venous thromboembolism Pipeline DMKC0148708 | Published on 07/01/2016
© Informa UK Ltd. This document is a licensed product and is not to be reproduced or redistributed
LATE STAGE DRUGS
betrixaban : Venous thromboembolism
PRODUCT PROFILE
Analyst Outlook
Betrixaban (Portola Pharmaceuticals) is expected to be the first novel oral anticoagulant (NOAC) drug
to gain approval for extended treatment of venous thromboembolism (VTE) in acutely ill patients. It is
currently enrolled in a Phase III trial, named APEX, which is evaluating the drug’s superiority over
current standard vitamin K antagonist (VKA)/enoxaparin treatment in critically ill patients. Betrixaban
has the potential to become the standard of care in this niche market segment. Datamonitor
Healthcare believes that betrixaban will easily penetrate this segment with minimal competition from
other NOAC molecules, owing to its superior clinical properties such as half-life, safety, dosage, and
minimal drug interactions in the intended patient population. Development of andexanet alfa (Portola
Pharmaceuticals), an in-house antidote, will further help with betrixaban’s adoption among physicians
concerned with the lack of a reversal agent.
Drug Overview
Betrixaban is an oral, once-daily inhibitor of factor Xa that catalyzes conversion of prothrombin to
thrombin (Medtrack, September 2015, Copyright Informa UK), preventing thrombosis (Portola
Pharmaceuticals, 2014a). Betrixaban is currently in Phase III development in the US and EU for the
prevention of VTE (BioMedTracker, Copyright 2015, reprinted with permission).
SAM
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