Download Idrabiotaparinux - Licensing opportunity

Idrabiotaparinux - Licensing opportunity
Unique once weekly anticoagulant with excellent compliance and tolerance
Idrabiotaparinux key points:

Free from drug interaction and side effect linked to oral formulation: no dietary
restriction, no gastro intestinal tract interaction, 100% bioavailability, low PK variability.

Once-a-week administration leading to better compliance and protection.

Availability of a specific and immediately active reversal agent (avidin) which simplifies
anticoagulation management (for instance in case of invasive procedure).

Efficacy and safety supported by completed large clinical trials.

Ready for registration within 20 months with limited investment

Significant upside with appropriate life cycle management

Patent protection up to 2026.
1
DRUG PROFILE
Idrabiotaparinux is a synthetic and selective indirect inhibitor of coagulation factor Xa via
antithrombin activation, administered once-weekly by subcutaneous injection. Its activity,
established in-vivo using different models of thrombosis, can be reversed by avidin, an
injectable protein that has been developed in parallel. Its very high affinity for biotin enables
avidin to immediately trap idrabiotaparinux which is consequently rapidly cleared from the
blood.
Idrabiotaparinux has a patent protection until September 2021, with possibly up to 5-year
extension depending on the countries. Patents have been filed for additional idrabiotaparinux
related inventions.
Pharmacokinetic data
Idrabiotaparinux s.c. is rapidly absorbed (tmax : 4 hours) and is 100% bioavailable.
Its pharmacokinetic profile is highly predictable and shows low inter-individual variability.
Idrabiotaparinux presents a small apparent volume of distribution, and a low total plasma
clearance allowing a once weekly administration.
Idrabiotaparinux is completely devoid of drug –drug interaction risk: it is neither a substrate
nor an inhibitor of CYP450 enzymes; and idrabiotaparinux is not an inducer of CYP1A,
CYP2C9 and CYP3A gene expression and enzyme activity.
In addition no interaction of idrabiotaparinux (as substrate and inhibitor) with P-gp
transporters has been observed.
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Clinical data
All together, idrabiotaparinux and avidin have been assessed in 14 pharmacology studies.
The overall outcomes confirm the good safety of both compounds. The large set of clinical
data accumulated with idrabiotaparinux (over 3500 patients exposed for more than 3 months)
provides a robust body of evidence supporting its efficacy and safety.
The net clinical benefit of idrabiotaparinux is supported by 3 completed clinical studies:

EQUINOX versus idraparinux, for the treatment of thromboembolic events in patients with
deep vein thrombosis (DVT).

CASSIOPEA versus vitamin K antagonist (VKA), for the treatment of thromboembolic
events in patients with pulmonary embolism (PE) with or without DVT.

BOREALIS versus VKA, for the prevention of stroke or non CNS Systemic Events in
patients with atrial fibrillation (AF)1.
EQUINOX showed:
 Similar efficacy profile between idrabiotaparinux and idraparinux (non biotinylated
pentasaccharide) in accordance with that observed in the van Gogh DVT study 2
conducted with idraparinux on DVT patients.
 Trend towards for less bleeding, especially major bleeding in the idrabiotaparinux arm.
 Effective and rapid neutralization of idrabiotaparinux activity following avidin
administration leading to a low residual anti-Xa activity without rebound of activity.
CASSIOPEA showed:
A similar efficacy to VKA at 3 and 6 months (p<0.0001) with a trend toward superiority
(ITT and per protocol analysis),
 A better bleeding profile at 3 months (p=0.0098 ITT but non significant according to the
per protocol analysis) and similar 6 months with a trend of superiority (odd ratio 0.81).
It has to be mentioned that analysis at 12 months showed superiority of efficacy of
idrabiotaparinux versus VKA together with a lower bleeding risk.

Efficacy results
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Bleeding results
15
idrabiotaparinux
Idrabiotaparinux
warfarin
Warfarin
idrabiotaparinux
Idrabiotaparinux
warfarin
Warfarin
9
8
End of treatment
Cumulative incidence (%)
Cumulative incidence (%)
7
6
End of treatment
5
4
10
5
3
2
1
Hazard ratio: 0.49
95% CI: 0.35 to 0.70
Hazard ratio: 0.79
95% CI: 0.62 to 1.00
0
0
0
30
60
90
120
1556
1565
1530
1535
1517
1518
1494
1478
Idrabio
Warfarin

1599
1603
150
180
210
240
270
300
330
360
1124
1105
1107
1088
1023
982
975
936
933
895
Time since randomization (days)
Number at Risk
1482
1466
1461
1450
1153
1139
0
30
60
90
120
1526
1505
1492
1470
1471
1452
1438
1418
Idrabio
Warfarin
1599
1603
150
180
210
240
270
300
330
360
1066
1057
1048
1045
967
951
920
910
878
872
Time since randomization (days)
Number at Risk
1415
1399
1395
1375
1100
1088
Idrabiotaparinux has a better and significant net clinical benefit at 3 and 6 months with a
protective effect up to 12 months without increase risk of bleeding.
1
BOREALIS-AF was discontinued in December 2009 (3774 patients enrolled) for strategic reason.
Non-inferiority study comparing idraparinux to LMWH followed by VKA
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SSR126517E – May 2011
Detailed results will be presented at the ISTH congress (Kyoto, July 2011).
Cassiopea together with Equinox brings strong evidence that idrabiotaparinux is an efficient
and safe treatment in secondary prevention of VTE indication and a good alternative to
current treatment.
2
DOMAIN OF APPLICATION
Thrombosis is a major cause of morbidity and mortality.
According to epidemiological data, VTE events rate is 0.18% of total population. Diagnosed
& alive DVT/PE patients in France, Germany, Italy, Spain, UK+US will be about 1.16 M in
2020. Recommended duration of treatment is 3 to 6 months depending on risk. Most patients
(90%) are treated for 6 months because of permanent risk factors, but also because of
hospital practice irrespective of their VTE risk factor.
The poor compliance of the patients to VKA is mainly explained by drug and food
interactions, responsible for increased adverse effects and leading to dietary restrictions.
There is a clear need for a drug with less frequent dosing, devoid of any drug-drug
interactions and dietary restrictions, able to improve patient compliance, quality of life and
health quality care.
In addition to the above mentioned targeted indication, there are several additional
indications that could be considered for idrabiotaparinux:
 Primary prevention of VTE: in medical patients and/or in cancer patients.
 Cardiac surgery with extra corporeal circulation.
With current data available, idrabiotaparinux could be registered for treatment and secondary
prevention of thromboembolic events in patients with PE and/orDVT.
3
REFERENCES
“Idraparinux versus standard therapy for venous thromboembolic disease”. The van Gogh Investigators, NEJM
2007, 357:1094-104.
“Convenience of the new long acting anticoagulant idraparinux versus vitamin K antagonist in patients with DVT”
M. Prins, abstract ISTH 2007.
“In-vitro and ex-vivo properties of long acting reversible oligosaccharide” J.P. Herault, abstract ISTH 2007.
“Reversible biotinylated oligosaccharide: a new approach for a better management of anticoagulant therapy” P.
Savi et all, JTH 2008 6:1697-1706.
“The efficacy and safety of re-administering avidin to reverse the anticoagulant activity of biotinylated idraparinux
in healthy subjects” M. Trellu, abstract ESC 2008.
“Reversibility of the anti-FXa activity of idrabiotaparinux (biotinylated idraparinux) by intravenous avidin infusion
“Paty et all, JTH 2010, 722-729.
“Efficacy and safety of once weekly subcutaneous idrabiotaparinux in the treatment of patients with symptomatic
deep venous thrombosis” The EQUINOX investigators, JTH 2010, 9:92-99.
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CONTACTS
Guy Claude
Anne Marie SIGOT
Vice President Out-Licensing &Special Projects
Senior Manager Out-licensing and Special Projects
Strategy & Business Development
Strategy & Business Development
Corporate Licenses
Corporate Licenses
[email protected]
[email protected]
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