Wanted – active substances!

The pharmaceutical industry is currently facing an acute shortage of active
substances. This, at least, is the view espoused by Dr. Andreas Wolter, Technical Director of the Hamburg-based Proligo Biochemie GmbH, in a statement on the drugs of the future. The message coming from most pharmaceutical boardrooms is very different, however. After all, to question the fruits of R&D would also mean questioning the way in which R&D budgets have shot up from approximately two billion dollars in 1980 to over 40 billion dollars in 2003. Does this spell failure for the highly industrialized model of pharmaceutical research that evolved out of the search for new drugs in the last century? Have the heady
ex-pectations placed by researchers and investors in such high-profile projects as high-throughput screening, the Human Genome Project and combinatorial chemistry — to name but a few — been disappointed? The fact is that after a period in which the USA was approving between 50 and 60 new substances a year, the 1990s saw the number of new approvals going into decline,
reaching a new low of just 18 new substances in 2002.

That there is a demand for new substances cannot be denied. But where is the search for  new leads going to take us in the 21st century? As in the past, drugs to combat those diseases that have not yet been adequately tackled — such as Alzheimer’s, Parkinson’s, cancer and AIDS — will be the ones with the most promising future ahead of them. Faced with ever more resistant strains of bacteria,
however, researchers are now having to retrain their sights on infectious diseases as well. Big pharma, meanwhile, is so straitjacketed when it comes to the search for new substances that it is having to rely ever more heavily on so-called blockbusters. Investors’ growth and profit expectations and an ageing product portfolio mean that all the big pharmaceutical groups are now under tremendous pressure to perform. The unwritten rule is that to be successful, any new drug developed today has to be able to generate annual sales of at least one billion dollars.
To find such a blockbuster, it is no longer sufficient merely to examine the “conventional” molecules that combinatorial chemistry turns out by the dozen — with the result that automated screening methods have had to be developed to filter out which of these dozens might indeed be useful. In future, or so Wolter believes, researchers will have to include “unconventional” substances in their R&D work as well. Among the most hopeful candidates in this category are peptides and synthetic nucleic acids. High production costs and problems with stability, presentation and unknown safety profiles mean that the latter, in particular, are rarely accorded the attention they deserve. Yet perhaps it is precisely here that the future of the pharmaceutical industry lies? The only thing that is not in doubt is that the search is as exciting as ever!

-Dr. Jörg R. Kempf-