Tuesday, December 27, 2011
Antibiotics in 2012
It is always risky to get into the business of predicting the future. But, to a certain extent, its what we all do for a living. So this year, I tried to put a few thoughts together on what might happen in 2012. I was also spurred by a summary of the ICAAC meeting published in Microbe Magazine where Jeff Fox contrasted my optimistic evaluation of the antibiotic pipeline to my “gloomy” blog.
The FDA –
It seems like the FDA has finally understood that they cannot continue to issue guidance documents requiring infeasible trial designs. What is less clear is whether they understand what “feasible” means to clinical developers and to industry. I am going out on a limb in predicting that rather than issue design requirements that are unworkable for urinary tract and intraabdominal infections, the FDA will delay guidance documents on these indications until they have a more clear idea of what will and will not work. If they don’t take this step, it will mean another several year cycle of unworkable guidance, additional workshops and advisory committee meetings and limbo for the industry leaving the US in an even less relevant position than it is today. Such a misstep will leave the new drugs for Gram negative infections now in or entering pivotal trials in these very indications in some FDA neverland but on relatively solid ground in Europe and everywhere else in the world. I don’t think that is where the FDA wants to be. So I’m predicting that they will avoid such an outcome.
I also predict that the FDA will try and achieve some understanding of pharmacometrics and how these methods can be used in various ways including as methods to define treatment effect for clinically relevant endpoints in various infectious disease indications.
I predict that the FDA will not come forth with a re-evaluation of generic antibiotics in terms of their risk to benefit ratios in spite of their promise to do so in 2006.
Innovative clinical trial designs –
I predict that the first truly innovative trial designs for antibiotics will be implemented in 2012 including superiority trials possibly even using adaptive Bayesian designs. Pharmacometrics will play an important role in the design of such approaches. These novel designs will be negotiated first in Europe with the US playing a distant second fiddle to the European regulators.
The markets -
2012 will be the year where the payor in mature markets begins to understand the value of antibiotics compared to high-priced drugs that only prolong lives weeks to months. Whether this will result in price adjustments for antibiotics already on the market – I doubt it. But prices for new drugs that offer clear advantages over generics or other marketed brand antibiotics will achieve higher prices. If these are supported by superiority data, such value will be easier to justify.
2012 will also see continued if slowing growth of antibiotic revenues in the emerging markets. Pressures from the global recession and internal economics will provide a braking of the rapid growth of the middle class in these economies and therefore will slow the growth in demand for branded antibiotics.
The pharmaceutical industry and antibiotics –
I predict that we will see continued evolution among the large pharma companies with divestitures to shrink these behemoths and with additional cost cutting M&A in 2012.
I predict that 2012 will see a continuing equilibrium at our current low point of only three large pharma companies truly engaged in antibiotics R&D. The three today are AZ, GSK and Sanofi (just getting back into the game). Novartis will remain schizophrenic with their discovery group fully engaged and their pharma group not so sure. Merck will continue with their slow, small program that is not large enough to really count. Any of these companies could depart the antibiotics arena at anytime, but several large companies are currently reconsidering the field and may even get back in attracted by market opportunities in the emerging economies.
I also predict that we will see continued emergence of small pharma along the lines of the Cubist model. Examples will be Trius and possibly Rib-X.
Biotechs developing antibiotics will continue to struggle. Those that have novel compounds active against resistant Gram-negative pathogens will be in the best position. Those with newer versions of older antibiotics targeting mainly Gram-positive or even Gram-positive and respiratory pathogens will have a more difficult time providing an exit for their investors.
Finally – regardless of where you are in the antibiotics world – I wish you a happy, healthy and prosperous 2012.