I've seen some odd things in my career, but a November 7 report in Drug Industry Daily may be one of the craziest. Maybe "Looney Tunes" crazy.
The article reports on discussions being held between the FDA and representatives of PhRMA concerning the development and launching of badly needed new antibiotics to combat bacterial pneumonia.
It is not news that many antibacterial agents are no longer effective against the pathogen for which they were intended. Drug resistant strains emerge so quickly that only one year after penicillin was introduced, bacteria resistant to it were observed. The same scenario is virtually guaranteed any time a new antibacterial agent is introduced, forcing medicine to run a no-win race with the bugs: New drug, resistance. Repeat as necessary.
There are ways to slow this cycle, such as more careful use of antibiotics and improved hospital procedures (hand washing, segregation of patients with resistant infections). But in the end, evolution will prevail, and the bacteria will continue to mutate in ways that will make them less susceptible to any drug that previously killed them.
This makes the discovery of new antibiotics essential--something that has been obvious for quite some time. The science to do this is hard enough, but when combined with sometimes-irrational regulatory requirements and subsequent economic burden, it is not surprising that most drug companies have left the area entirely.
And the ongoing discussions between PhRMA and the FDA certainly won't help.
The groups have a "minor" difference of opinion on how to measure the clinical success of potential antibiotics. A 2009 draft guidance prepared by the FDA's anti-infective drug expert panel illustrates this perfectly.
The panel's recommendation for evaluating new drugs for pneumonia is mind boggling. In its present form it requires evidence that the new drug works (fair enough). But some panel members are insisting that sufficiently precise evidence can only be determined by excluding people that have ever taken anyantibiotic. Yes--you heard me.
As if it weren't already difficult, expensive and time-consuming enough to run drug trials, now companies and clinical investigators will have to dig up a large group of people never treated with amoxicillin or erythromycin or all the others that pretty much everyone has taken at some point. Where will these people be found? Venus?
One of the PhRMA representatives put it bluntly: "To eliminate all prior antibiotics will virtually eliminate the US."
This is not the first time that the FDA has acted bizarrely in such matters. In the 1990s the antibacterial group at Wyeth was trying to get approval for a new antibiotic that we had discovered a few years earlier. This drug, later named Tygacil, was effective against a variety of resistant organisms, including MRSA.
But Wyeth ran into a moving target at the FDA, who all of a sudden insisted that the number of patients needed to show efficacy at a certain statistical level should be three-fold higher than expected, making the trials prohibitively time consuming and expensive. Wyeth decided to withdraw the drug.
It took a Herculean effort by Dr. David Shlaes, the former director of the infectious disease research section to convince the FDA that the additional statistical power (more patients) they were requiring was unreasonable and would not contribute anything to the study, except to stop it. The FDA relented, and Tygacil was launched in 2005.
Unfortunately, it is clear the controversy over new pneumonia drugs is not an isolated event--it is apparently a misguided and dangerous mindset that will virtually guarantee a continued exodus from the field. As Dr. Shlaes puts it, "In the decade since our discussion with FDA over Tygacil, they have abandoned the role of regulator to become a blocked door. The FDA needs to get back to rational regulation so that we won't face a time when people in Beijing have access to new antibiotics while those in Washington do not."
This sums it up perfectly. If we really want to have new effective antibiotics, "looney" regulatory policies must be avoided. Th-th-th-that's all folks.