David's New Book

Sunday, July 22, 2012

Antibiotic Uppers





I was inspired this week by a few news articles and blogs that appeared recently.  One in particular was a piece by Maryn McKenna, author of Superbug.  She writes about the frustration of activists dealing with political and social inertia. I have spent the last several years discussing the perfect storm of factors working against the discovery and development of new antibiotics needed in our fight against antibiotic-resistant pathogens. It is fair to say that the last 10 years have been mostly downers in this regard.  So I can certainly empathize with the difficulties of trying to move boulders uphill. 

But I also have my own moments of optimism (perhaps misguided) – like now.  Over the last year we have seen the European regulatory agency, EMA, leading the way to the feasible and rational design of clinical trials to support the approval of new antibiotics.  The FDA has said they will reboot their entire process (which probably cannot get worse) (famous last words).  Since regulatory reform was one of the key potentially reversible roadblocks to the development of new antibiotics, I believe these developments are very positive and I am becoming optimistic about the future of antibiotics.

We have recently seen very significant government investments in antibiotic R&D including funding through BARDA to cover at least a portion of the expensive phase III trials to get antibiotics to market approval. GSK was awarded  nearly $100 million in support of its ‘052 antibiotic active against many resistant pathogens  (unfortunately, those trials have now been halted).  Tetraphase was awarded up to $67 million in support of TP-434 (see below).  The Innovative Medicines Initiative in Europe has also just announced similar important investments in antibiotic R&D (see the last blog). These very important investments provide additional, clear incentives for the continued discovery and development of new antibiotics.

Another source of optimism to me is the continued rapid growth in antibiotic sales in the emerging markets. Antibiotic sales in these markets have already outpaced the US market by over 30% and are rapidly approaching the point where they will be equal to Europe and the US combined.   These markets will become more and more attractive to companies who are poised to exploit them.  This indicates that more companies will re-enter the antibiotic R&D arena as Sanofi-
Aventis has recently done.  To me, this makes the patent extension included in the GAIN act (recently signed into law by President Obama) totally irrelevant except for those small companies who are developing products with otherwise short patent lives.

We now have a number of antibiotics that will be effective against at least some of the most fearsome resistant Gram-negative pathogens in the late stage pipeline.  These include ceftazidime-avibactam from Astra-Zeneca which will be active against KPC-producing organisms resistant to carbapenems and virtually all other antibiotics and ceftolozane from Cubist – a drug active against many highly resistant Pseudomonas strains. Tetraphase should soon be completing their phase II study of TP-434, a tetracycline active against many multiply-resistant Gram negative pathogens including Acinetobacter and which is available orally as well as IV. There are other antibiotics about to enter late stage development with complementary activity against other multiply-resistant pathogens as well. 

So, I am now in one of my more optimistic moods regarding the future of antibiotic R&D.  But of course this all depends on; a successful FDA reboot; a large PhRMA industry that sees an advantage in rising antibiotic sales in emerging economies in spite of their continued need to slash and burn to make up for patent losses; and perhaps, even on welcoming public markets for small biotechs desiring to go it alone.  So, I guess I am a somewhat cynical optimist after all.