| The
antithrombotics market is growing quickly from a relatively
low base. Dollar sales have more than doubled in the past
five years and there is considerable potential for further
growth. According to a major new study by IMS Health, however,
ongoing cost-containment issues and often conservative attitudes
to the risk/benefit profiles of the products involved will
temper the market’s long-term prospects.
Sales
of the ATC B1 class of drugs that make up the antithrombotics
market reached almost $13 billion in the 12 months to March
2004, reflecting a compound annual growth rate of 18% since
1999. Nearly half of these sales were generated in the US,
the leading market and 3.5 times larger than its nearest
rival, Japan. In Europe, France and Germany dominate, each
with twice the sales of Italy and the UK. Together, these
six markets account for more than 80% of global antithrombotic
sales.
Dominant
therapies
Antithrombotics
consist of two distinct groups:
The
market is dominated by platelet aggregation inhibitors and
heparins, which account for 58% and 28% of sales respectively.
This compares with the 5% share held by vitamin K antagonists
and by fibrinolytics and less than 2% each for direct thrombin
inhibitors and other products – though the latter two are
growing rapidly.
The
dominant platelet aggregation inhibitor – and clear overall
market leader – is Plavix (clopidogrel), from sanofi-aventis
and Bristol-Myers Squibb. The ticlopidine analogue
is indicated for the prevention of atherosclerotic events
in patients with a history of ischaemic stroke, thrombosis,
myocardial infarction or established peripheral arterial
disease. Growth of Plavix has been impressive, with sales
reaching nearly $4 billion in 2004. The prospect of a Japanese
launch by licensee Daiichi in 2005 offers the potential
for further sales expansion although this is countered by
pending US patent challenges: Apotex and Dr Reddy’s have
filed ANDAs with the FDA for generic clopidogrel, although
sanofi-aventis has filed suits against both.
Leading
antithrombotic brands
Market share for 12 months to March 2004
Source:
IMS
MIDAS
NB. 'Others' includes generics
Second
placed Lovenox (enoxaparin), also from sanofi-aventis,
holds a strong position in the global antithrombotics market.
Sales exceeded $2.2 billion in 2004, giving the low molecular
weight heparin (LMWH) a 61% share of the heparins sub-class.
Its approved indications include the prevention of deep
vein thrombosis (DVT) following surgery, treatment of established
DVT, the prevention of clotting in extracorporeal circulation
during haemodialysis, and acute treatment of unstable angina
and non-Q-wave MI.
Despite
several clinical studies supporting Lovenox and differentiating
the drug from other products, the threat of generic competition
hangs over the brand. Litigation proceedings are underway
against Teva and Amphastar after both submitted ANDAs with
the FDA. Given the complex structure of Lovenox, however,
analysts have suggested that any company will have difficulty
proving generic equivalence.
Pletaal
(cilostazol) is a phosphodiesterase inhibitor with platelet
anti-aggregant and vasodilator activity, predominantly indicated
for the treatment of intermittent claudication. It is also
marketed in Brazil for the prevention of stroke and has
been approved in Japan for treating recurrent cerebral infarcts.
The key markets of Japan and the US (where the product is
co-promoted by Otsuka and Pfizer) account for the majority
of sales. Following the approval of generic forms of cilostazol
in the US in late 2004, this brand is expected to lose ground.
Exanta
– gold standard or non-starter?
Recent
improvements in antithrombotic therapy have been small and
incremental rather than true step changes, according to
the expert panel interviewed for the study. Among the latest
new entrants, AstraZeneca’s direct thrombin inhibitor Exanta
(ximelagatran) has received the most attention.
Since
completing the EU mutual recognition procedure in May 2004,
Exanta has been launched in a range of European markets
for short-term use in the prevention of venous thromboembolism
in major elective orthopaedic surgery. Touted as the potential
new gold standard therapy for many, if not all, the current
antithrombotic indications, Exanta is expected to take market
share from warfarin
(BMS' Coumadin in the US), the heparins and aspirin.
With its US approval placed on hold in late 2004 following
FDA concerns over safety and efficacy, however, analysts
are now warning that the drug’s head start over others in
development could be lost.
The
outlook
Plavix
has shown that there may still be room for effective new
antithrombotics supported by a workable price. In such a
relatively well-served market as this, however, and given
the current strong focus on cost-containment, achieving
a high price for new products will not be easy, even with
proof of additional benefits. While premium prices are theoretically
available for innovative or breakthrough products in some
markets, the qualifying requirements are strict and it is
unlikely that more than a handful of products across all
therapeutic categories will benefit each year. In the case
of antithrombotics, authorities will be looking closely
at pricing in relation to high patient volume (which continues
to increase with the ageing population), as well as the
low prices of many existing products. The study references
France, where, despite being heralded as significant improvements
in therapy, recently introduced antithrombotic agents have
received disappointing assessments.
The
issue of price will be compounded as leading brands Plavix
and Lovenox lose patent protection and generics start to
enter the market. Traditionally affecting only the original
brand, generics are increasingly showing signs of impacting
other products in the same therapeutic class. Their introduction
is therefore likely to depress price levels across the entire
antithrombotics market, driving even closer payer scrutiny
and emphasis on clinical benefits in relation to existing
products. This will be particularly relevant in reference
priced countries like Germany,
where question marks still remain around the grouping of
antithrombotics and likely price comparators for new market
entrants. Should the outcome of this be unfavourable, knock
on effects throughout Europe are possible as payers resist
paying more than their counterparts in Germany.
Focusing
efforts
With
such a large number of patients treated in the community,
there are major potential gains for a new treatment that
can reduce the need for titration and monitoring as well
as demands on treatment infrastructure – although convenience
alone will not be enough.
Manufacturers
looking to succeed in this market will need to focus on
patient groups characterised by a high level of risk, including
those with the most serious health problems who place the
greatest burden on healthcare resources.
Given
the risks of bleeding associated with effective antithrombotics,
clinical trials of new agents must focus on high-risk groups
in order to balance out the risk/benefit profile. Focusing
on the ‘average’ patient will not be beneficial; new, higher
priced therapies will need to demonstrate better delivery
of benefits for more costly patients.
Panellists
interviewed for the study felt that physicians should make
better use of sophisticated diagnostic techniques to identify
and treat high-risk patients earlier. Similarly, the treatment
infrastructure must include physicians who are able to manage
these high-risk patients. If such an approach, based on
centres of excellence, can show results with new therapies
in difficult-to-treat patients, this may create momentum,
yielding broader use of the products involved. When physicians
can see product benefits in clinical practice, they may
extend the range of patients to treat.
IMS
Therapy Report: Thrombosis looks at the performances
of the major companies and products in each of 10 major
world markets, and includes analysis of pipeline compounds
and insights into the future performance of the therapy
area from key players. For more information on this CD-ROM
product, please visit www.imstherapyreports.com, or alternatively,
contact Richard
Mee via e-mail or call +44 207 393 5757. |
