Stratanalysis Document

AZ s Brilinta Reports Favorable Trial III Results

Stratanalysis
Sept 07, 2009

Strategic Analysis and Tech Solutions Limited www.stratanalysis.com

 AZ s Brilinta Reports Favorable Trial III Results
Brilinta Beats Plavix in Efficacy and Reversible Action

On 30th August, 2009, AstraZeneca announced results from the Phase III head to head trial, PLATO1
which showed that ticagrelor (Brilinta) has achieved greater efficacy based on the primary endpoint,
reduction of cardiovascular events (CV death, MI, stroke) over clopidogrel (Plavix/Iscover)
Brilinta Shows
Patients with acute coronary syndrome (ACS) who took Brilinta were 16% less likely than
Better Efficacy
those on Plavix to die from cardiovascular causes or suffer a heart attack or stroke
Than Plavix
Ticagrelor is an investigational oral antiplatelet treatment for ACS and is the first reversibly binding oral
Without Major adenosine diphosphate (ADP) receptor antagonist
Bleed Risk AstraZeneca believes this medicine has an edge in part because its action can be reversed,
meaning that heart patients who take Brilinta can be prepared for any necessary surgery much
quicker, without excessive bleeding risk

The global antithrombotic2 market is expected to grow to USD 22 BN by 2017 and has demonstrated a
steady growth with CAGR of 8% over the 2004-07 period
The major player in the anti-coagulant market is Plavix, sold by Sanofi-Aventis and Bristol-Myers
Antithrombotic Squibb, which sold approximately USD 9 BN last year
Market Players Eli Lilly and Daiichi Sankyo's recently launched Effient (prasugrel) has also outperformed Plavix
in tests, however it is hampered by a strict warning on bleeding risks
Another competitor is Coumadin (warfarin) manufactured and sold by Bristol-Myers Squibb,
which is already available in generic form

Note: 1A Study of Platelet Inhibition and Patient Outcomes; 2Thrombolytics, anticoagulants and anti-platelet drugs
Source: Reuters News, Business Week, Wall Street Journal, Datamonitor Research
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 AZ s Brilinta Reports Favorable Trial III Results
Global Antithrombotics Market

Predicted Global Revenues for Antithrombotics, 2005-2017

25
USD 22 BN2
Global Sales (USD BN)

20 CAGR USD 17.9 BN1

5.08

15 USD 13.3 BN1

10

0
2005 2007 2009 2011 2017
Years

Global Market:
The global antithrombotic market sales is predicted to reach USD 22 billion by 2017
o The growth is expected to be triggered by the introduction of new agents into the market, such as prasugrel, which
would offer significant improvements over the current standards of care (clopidogrel and warfarin)
The US antithrombotic market as a percent of the global market is predicted to decrease from 55% in 2007 to 49% by
2017, due to patent expiries in the EU not affecting brand sales to the same extent as in the US
Sales revenue from the forthcoming launches of innovative novel agents in this market is expected to dampen the
commercial impact from generic erosion of the current blockbuster brands

Note: 1As predicted in 2005; 2 As predicted in 2008

Source: Datamonitor Research
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 AZ s Brilinta Reports Favorable Trial III Results
Brilinta Vs Plavix PLATO and DISPERSE trials (1/2)

End Points Brilinta Plavix Comments

Death from vascular Brilinta shows 16.2% improvement over Plavix in death from
9.8% 11.7%
causes, MI or stroke vascular causes, MI or stroke
Brilinta shows 23.7% improvement over Plavix in preventing
Death from any cause 4.5% 5.9%
death from any cause

Brilinta shows 15.9% improvement over Plavix in occurrence of

Myocardial Infarction 5.8% 6.9%
myocardial infarction

Plavix is 13.3% more effective than Brilinta in prevention of

Stroke 1.5% 1.3%
stroke

End Points Brilinta Plavix

Dosage Twice a day oral dosage One-daily oral dosage

Does not require metabolic conversion making action Requires hepatic conversion, leading to delay in onset of
Onset of Action
faster action

Reversible effect suitable for chronic use in patients with Its active metabolite binds irreversibly to P2Y12 receptors
Reversibility of Action
acute coronary syndromes (ACS) such that recovery of platelet function is precluded

Over 12 months, patients taking ticagrelor had fewer heart attacks and strokes compared with patients taking clopidogrel (9.8%
versus 11.7%). Moreover, fewer patients taking ticagrelor died compared with patients taking clopidogrel (4.5 % versus 5.9%)
Due to easy reversibility, heart patients who take Brilinta can be prepared for any necessary surgery much sooner, without
excessive bleeding risk as compared to Plavix
However, Brilinta has a twice daily dosage compared to Plavix

Source: NEJM, Business Week, European Society of Cardiology

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 AZ s Brilinta Reports Favorable Trial III Results
Brilinta Vs Plavix PLATO and DISPERSE trials (2/2)

End Points Brilinta Plavix Comments

Patients taking Brilinta are 15.5% more likely to have
Major Bleeding 4.5% 3.8% spontaneous intracranial and gastrointestinal bleeding than
people taking Plavix
Brilinta shows higher occurrences of Dyspnea (44.4%)
Dyspnea 13.8% 7.8%
compared to Plavix amongst patients

Shortness of breath is more common in patients taking Brilinta

Shortness of Breath 14.2% 9.2%
(35.2%) compared with patients taking Plavix

DISPERSE Overall Total Bleeding Comparison

Patients taking Brilinta are more likely to have (Minor bleeds without major bleeding)
15
spontaneous intracranial and gastrointestinal bleeding
than people taking Plavix

Total Bleeding Rate (%)

10.2% 10.2%
10 9.2%
A segment of patients with asthmatic co-morbidity or any
other respiratory disease might not be able to take
Brilinta, as shortness of breath is more common in 5
patients taking Brilinta compared with patients taking
Plavix
0
There was also an excess of ventricular pauses
Clopidogrel 75mg AZD6140 90mg AZD6140 180mg
in patients treated with ticagrelor as compared to
qd bid bid
clopidogrel
Major Bleeds Minor Bleeds

Source: NEJM, Business Week, American College of Cardiology

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 AZ s Brilinta Reports Favorable Trial III Results
Stratanalysis Viewpoints and Analysis

AZ expects Brilinta peak sales to be about USD 2.2 Bn by 2014

Advantage AZ
This would imply earnings of about USD 850 MM for the company

Eli Lilly and Daiichi Sankyo had previously cut their sales projections for Effient to half of the
Disadvantage Eli original USD 1.5 Bn
Lilly and Daiichi With a new high-performing blood thinner (minus the bleeding warning on the label)
Sankyo's slated for launch one year after the launch of Effient, it is possible that the sales
projections will be cut down to a much smaller figure

Disadvantage Brilinta might be able to make a dent on Plavix sales in case it is launched before the latter
Sanofi-Aventis goes off-patent in 2011
and Bristol- Plavix sales were apprx. USD 9 Bn last year and this will only be challenged by
Myers Squibb's Effient with an excessive bleeding warning label next year

Brilinta launch before Plavix going off-patent might mean that generic Plavix manufacturers
acquire a smaller market share
Scenario I (Brilinta launches >3 months before Plavix goes off patent): A good
chunk of Plavix patients will move to the more efficacious Brilinta. Once Plavix goes
Plavix Generic off patent, some of them might return to the then low cost generic Plavix. However,
Manufacturers patients who experience better results with Brilinta will stick to the new drug
Scenario II (Brilinta launches after Plavix goes off patent): Brilinta will have to pick
up patients on low cost Plavix. This might prove to be difficult because of the huge
cost dfferential

Source: Stratanalysis Research

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