David's New Book

Monday, March 28, 2016

Congress, FDA and Antibiotics

I hope everyone had a happy Easter holiday.  Its raining here today, and under these depressing conditions, I find myself thinking back to the Ketek scandal of 2006 and wondering about the continued meddling of Congress under the influence of Public Citizen in antibiotic trial design issues. What am I talking about? See my book chapter on the FDA. (I apologize, but they still charge $29 for the chapter download).  Basically, in 2006, after a few cases of serious liver toxicity caused by Ketek, a new antibiotic active against resistant bacterial pathogens, the FDA was threatened with congressional investigations on the antibiotic trial designs that led to the Ketek approval.  The FDA went into defense mode, people were fired or transferred and antibiotic development went from slow to non-existent for the next six years.

Fast forward to 2016.  The FDA rebooted its antibiotic development program in 2012 and since then we have seen a flurry of antibiotic approvals including two new antibiotics for the treatment of serious Gram-negative infections.  One of these, ceftazidime-avibactam (near and dear to me), was approved mainly based on phase II data (even though it met a 15% NI margin and top line data from one phase III trial was available). This was a historic first for the FDA.  

In its reboot process, the FDA released a guidance for the development of antibiotics for patients with unmet medical needs. This guidance calls for streamlined trial designs to get needed antibiotics to the patients who need them quickly. It was under this guidance that ceftazidime-avibactam was approved based on a smaller data set than any other antibiotic in modern times.  I now find that the designs embodied in this guidance document that would allow these streamlined approaches are threatened once again by Public Citizen and its congressional meddlers. This time, I don’t know who it is in congress that is involved. But the stream of questions from congresspersons and veiled threats of congressional investigations harken back to the dark days of the Ketek scandal and the FDA once again may respond by ducking back into its shell. And when that happens, you can forget about new trial designs for rare infections, pathogen specific antibiotics and other needed new approaches to antimicrobial therapy.


The PATH act is currently in mark-up in the senate. It is sponsored by Orin Hatch of unregulated supplements fame (probably not a good thing). There are many moving parts here including LPAD, ADAPT etc – but PATH has the language I think the FDA wants and I like it better. It provides congressional authority by law for the FDA to carry out much of what is already outlined in the FDA’s unmet need guidance.  The FDA believes (in my opinion) that this will protect them from congressional meddling and threats of investigation for their decisions regarding antibiotic development and approval. I am not at all convinced that this is the case.  I also believe that the FDA already has the statutory authority to do what the PATH act outlines.  But – the FDA wants this – and – at this point, if it helps them, it helps us. So – write your congressional representatives. At the same time, please ask them to leave the FDA alone on antibiotic development issues and ask them to ask their colleagues to do the same.