Roche has recently been taking considerable heat for not providing certain clinical data on Tamiflu (oseltamivir), its flu drug that has been on the market since 1999. During the 2009 H1N1 flu scare, hospitals, governments and many individuals were panic buying it, and some of them are not too happy about spending a load of money on something that doesn't work very well.
If taken within the first two days of coming down with the flu, Tamiflu seems to knock off about one day (7 days down to 6) of the illness. It may also have some effect in reducing symptoms, but this is not clear. It also has some fairly nasty side effects. Given all of this, I have always considered it to be a marginal drug at best.
And if it wasn't especially effective before, it is becoming even less so now. To understand why, one needs to know a little about how viruses work.
Viruses are obligate parasites-- they can only replicate within the host cell that they infect. They have have come up with some fiendishly clever ways to survive and prosper.
All viruses use more or less this same strategy to replicate: After the virus binds to a particular receptor on the surface of its host cell (in the case of flu, these are lung and nasal cells) it enters the cell and "hijacks" the normal reproductive machinery of the host cell, tricking it into making the DNA or RNA of the virus instead of that of the cell. Then, using enzymes that are contained in the virus, new viral particles are assembled within the cell and burst in large numbers, where they seek new host cells, spreading the infection.
If any of these steps is short circuited by the presence of a drug, replication will stop. These discreet steps are referred to as targets, and most antiviral drugs (HIV being the best example) work by inhibiting a specific viral target.
The discovery of Tamiflu, as flawed as it is, represents a nice example of one of the spiffier technologies used in drug discovery--computer assisted drug design (CADD). In this case, the technique was used to design molecules that could interfere with the function of one of flu's essential enzymes--neuramidase.
Oseltamivir binds to and inhibits neuramidase (the "N" in H1N1; the "H" stands for hemagglutinin, and good luck using that bad boy in Scrabble), thus preventing it from doing its job--acting like a pair of molecular scissors. After the flu virus is finished replicating within a cell, the new viruses burst through the host cell membrane, however, they are still stuck to the membrane until neuramidase comes along-- cutting off the new flu virus particles allowing them up escape and infect other cells thus perpetuating the infection. If neuramidase doesn't function, the new viruses won't be released, and the infection can't spread.
Below is an example of CADD--oseltamivir (the mostly pink blob in the middle) bound to neuramidase (the colored ribbons). Using information derived from a technique called x-ray crystallography, chemists were able to visualize at the atomic level (in three dimensions) a set of imaginary molecules that would bind tightly and inhibit neuramidase. This led them to synthesize a series of molecules that did just that. One of these molecules was later named oseltamivir. And it worked--at least a little.
CADD has led to the discovery of many drugs--especially for HIV, and the science involved is elegant. But viruses don't much care for elegance--they simply want to replicate. And even the most scientifically rigorous and creative technology can be outdone by the tricks that the virus has up its sleeve. The most effective trick in its arsenal is mutation--a slight change in the structure of the virus or one of its components.
Most viruses mutate like crazy, and the best way to encourage them to do this is by exposing them to a single drug that inhibits the replication of the natural strain of the virus. Doing this promotes the growth of mutant strains that are less sensitive to the drug, allowing them to flourish in the absence of the natural strain--as perfect an example of evolution as you'll ever find.
This was never more clear than in 1987 when AZT, the first HIV inhibitor was approved for treatment of AIDS. It was a complete flop. Although AZT did inhibit the growth of HIV for a short period of time, the virus rapidly mutated rendering AZT essentially useless.
And this is exactly what is happening with Tamiflu.
According to a March 2012 paper in Lancet Infectious Diseases, in 2007/2008, a type A (H1N1) influenza virus was found to have developed resistance to Tamiflu. Within one year, this strain of flu had spread globally, such that virtually every strain of this virus around the world was resistant to this drug.
Whether other strains of flu will develop resistance of this magnitude remains to be seen, but Tamiflu is clearly an imperfect drug that may be of little or no use in the future.
Roll up your sleeve.