E-DRUG: Is that it, then, for blockbuster drugs?
[Serious criticism for big farma, from the Lancet, Volume 364 Issue 9440, 25
Sept 2004, page 1100. Copied as fair use; WB]
Is that it, then, for blockbuster drugs?
2 weeks ago, an Advisory Committee to the US Food and Drug Administration (FDA)
rejected an application for ximelagatran, AstraZeneca's new thrombin inhibitor.
The Committee cited worries about liver toxicity, which has led to three
deaths, together with doubts about the company's plans to monitor and manage
No one doubts that an alternative to the hard to use, and consequently
underused, warfarin is needed. Ximelagatran was to be indicated to prevent
venous thomboembolism, especially after total knee replacement, and to prevent
strokes in patients with atrial fibrillation.
Ximelagatran has stumbled at this regulatory hurdle, for the moment at least;
the company is urgently negotiating with the FDA. Does this failure for another
hoped-for blockbuster drug reflect a greater malaise in the pharmaceutical
industry and auger badly for the future? Quite probably, yes. The age of the
blockbuster drug seems over, or at least in its last days.
The problem is that the pharmaceutical industry has not been as innovative as
it claims to be, a failing reflected in the falling stock-market performance of
many large companies. Most of the big pharmaceutical manufacturers spend more
on marketing than on research and development. In last-ditch flings at seeking
new markets, the drugs industry can only come up with new indications for old
drugs and me-too compounds to barge into existing markets.
What has gone so wrong? Are all the known drug receptors saturated with
existing compounds, as it were, such that no new drugs are needed? Certainly
not, since current treatments are not effective enough, and safety profiles
could well be improved. Drug companies actively research for new ways to
interact with known receptors and seek out new receptors. But the development
road is long, stony, and expensive, as seen with ximelagatran.
The traditional route to drug discovery, the old pharmacology of testing
analogues of active drugs or the slightly newer pharmacology of mass screenings
in chemical libraries, is not yet over. But neither has rational drug
design--the new pharmacology of characterising the receptor and making a drug
to fit--come up with a blockbuster, although it may do one day. Such rational
research has led to licensed drugs, but they are mostly for rare diseases (eg,
imatinib for gastrointestinal stromal tumours) or are barely effective, even in
combination with traditional therapies (eg, trastuzumab for some advanced
The challenge is set for drug companies to become truly innovative. A good
start would be to forget the me-too market (after compounds three and four are
licensed) and to go and find those receptors, old and new, and the genuinely
new compounds to interact with them. * The Lancet