DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

70
15
Number of Approved NMEs ( )
R&D Expenditures (in billions US$) ( )
60
50
40
30
20
10
0
1970
1974
only 67 (14%) were considered by the FDA to be new molecular
entities. Second, to the extent that some me-too drugs are more
expensive than the older versions they seek to replace, the costs of
healthcare are increased without corresponding benefit to patients.
Nevertheless, for some patients, me-too drugs may have better efficacy
or fewer side effects or promote compliance with the treatment
regimen. For example, the me-too that can be taken but once a day
and not more frequently is convenient and promotes compliance.
Some “me-toos” add great value from a business and medical point
of view. Atorvastatin was the seventh statin to be introduced to market;
it subsequently became the best-selling drug in the world.
Introduction of similar products in other industries is viewed
as healthy competition. Such competition becomes most evident in
the pharmaceutical business when one or more members of a group
loses patent protection. Now that non-proprietary versions of simvastatin
are available, sales of atorvastatin are declining. Billions of
dollars might be saved, likely with little loss of benefit, if nonproprietary
simvastatin were substituted for proprietary atorvastatin, with
appropriate adjustment of dosages.
Critics of the pharmaceutical companies argue
that they are not innovative and do not take risks and,
further, that medical progress is actually slowed by their
excessive concentration on me-too products. Figure 1–2
summarizes a few of the facts behind this and some of
the other arguments just discussed. Clearly, smaller
numbers of new molecular entities have been approved
by the FDA over the past decade, despite the industry’s
1978
1982
1986
Figure 1–2. The cost of drug invention is rising dramatically while productivity is declining. The past several decades have seen enormous
increases in spending for research and development by the pharmaceutical industry. While this was associated with increasing
numbers of new molecular entities (NMEs) approved for clinical use during the latter years of the 20th century, this trend has been
reversed over the past decade, leading to unsustainable costs per new molecular entity approved by the FDA. The peak in the mid-
1990s was caused by the advent of PDUFA (see text), which facilitated elimination of a backlog.
1990
1994
1998
enormous investment in research and development.
This disconnect has occurred at a time when combinatorial
chemistry was blooming, the human genome was
being sequenced, highly automated techniques of
screening were being developed, and new techniques
of molecular biology and genetics were offering novel
insights into the pathophysiology of human disease.
Some blame mismanagement of the companies. Some
say that industry science is not of high quality, an argument
readily refuted. Some believe that the low-hanging
fruit has been plucked, that drugs for complex diseases,
such as neural degeneration or psychiatric and
behavioral disorders, will be harder to develop. The
biotechnology industry has had its successes, especially
in exploiting relatively obvious opportunities that the
new recombinant DNA technologies made available
(e.g., insulin, growth hormone, erythropoietin, and
more recently, monoclonal antibodies to approachable
extracellular targets). Despite their innovations, the
biotechnology companies have not, on balance, been
more efficient at drug invention or discovery than the
traditional major pharmaceutical companies.
Whatever the answers, the trends evident in
Figure 1–2 must be reversed (Garnier, 2008). The current
path will not sustain today’s companies as they face
a major wave of patent expirations over the next several
2002
2006
CHAPTER 1
DRUG INVENTION AND THE PHARMACEUTICAL INDUSTRY