TRENDS AND CONSIDERATIONS IN GLOBAL CARDIOVASCULAR DRUG DEVELOPMENT | Page 5

For CV drugs developed from 2005 to 2009, mean clinical time was 6.5 years and
approval time was 1.3, for a total development time of 7.8 years. Clinical
development times were longer in only two categories: antineoplastic drugs at 6.9
years, and CNS drugs at 8.1 years.

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For all drugs developed from 1999 to 2004, the

likelihood that an agent entering Phase I would reach the market was only 16
percent; the success rate for CV drugs was a dismal 7 percent.

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A recent analysis of development time and cost for approved cardiovascular,
obesity and diabetes drugs showed that 90 percent of total costs were typically
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spent on Phase III trials. The authors examined trial size and cost for Xarelto and
Eliquis, two factor Xa inhibitors with promise to advance treatment for acute
coronary syndrome, atrial fibrillation and venous thrombosis. Together, Xarelto
and Eliquis trials studied more than 130,000 patients at a total estimated cost of
more than $6 billion. The authors suggest that high development costs have a
chilling effect on drug innovations in areas of greatest need. Comparing the
number of drugs in development in 2010 to the number of U.S. deaths in 2009 for
12 major indications, only three cardiovascular drugs were being developed per
10,000 patients, compared to 12.4 drugs for Alzheimer’s, 15.4 drugs for all types of
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cancer, and 28.2 therapies for diabetes.

Cardiovascular device development is similarly challenged by increasing
regulatory demands. In the U.S., medical devices are approved either through the
Premarket Approval (PMA) process that requires submission of clinical data, or
through the simpler 510(k) review process that does not. Recent safety recalls of
devices are driving increasingly rigorous safety scrutiny, and uncertainties
surrounding regulatory change (for example, reauthorization of the Medical
Device User Fee Amendments) are increasing review times. The average total time
for FDA review under the 510(k) procedure rose more than 55 percent, from 90
days in 2005 to 140 days in 2012.

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Dhruva and Redberg note that the PMA route

would provide the most safety information, and yet only 1 percent of devices
currently undergo the PMA process.

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Device approval tends to be faster in Europe

but registration requires less clinical and safety data.

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