Thursday, May 23, 2013

BARDA strikes again!

In a startling new development, the Department of Health and Human Services just announced the establishment of a collaborative agreement with Glaxo Smith Kline for the development of a portfolio of products targeting both agents of bioterror and antibiotic resistance.  The first tranche of monies based on this agreement is $40 million with the possibility of up to $200 million in funding if the contract is renewed. The form of the collaboration is flexible allowing individual products to move in and out of the portfolio during the term of the agreement. It looks like there will be a joint management committee just like what commonly occurs with intra-pharma collaborations.  If everyone knows what they are doing, this seems like an outstanding approach to establishing a model for a public private venture for antibiotic research.  Kudos to BARDA and GSK for making this happen.

Now, during the sequester, we just have to disseminate this model to other companies.  GSK isn’t the only large or small company with promising antibiotic research programs that could be applied to both bioterror and to antibiotic resistant infections. BARDA – if you’re having trouble identifying these companies – let me know – I’ll help.

Another interesting aspect of the press release from HHS noted what they said was a similar endeavor in Europe through Innovative Medicines Initiative.  But this is totally different in that it establishes monies contributed by EFPIA (European PhRMA) members and by the EU Commission (EU taxpayers) to be distributed to grant applicants.  But everyone is (as far as I know) forced to partner with an EFPIA member somehow. BARDA seems to not be constrained in this way at all.  The BARDA approach seems far superior to me.  The question is – how much budget do they have and is there anyone out there willing to enter in to such an agreement with them?  It seems like a great deal to me.

As you can see – I am very excited by this announcement and I only hope this offers a truly new way forward for PhRMA, large and small, to do business with government.  I also hope that this will act as another incentive to bring companies back into the field of antibiotic R&D.  We desperately need them.

So, once again, BARDA – kudos and thanks!

Friday, May 10, 2013

Who Will Do This?

The National Institutes of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) in the US is now very aware of the crisis of antibiotic resistance and the lack of new antibiotics in the pipeline to address this public health threat.  This was not always the case.  As I wrote in my book, a number of us carried out a study back in the 1980s showing at least a 30-year neglect of antibiotics research at NIH.  Things did not turn around there until 2006.

NIH now offers grants to support early research going up through phase I development and beyond in many cases.  They also offer a variety of service resources such as manufacturing, toxicological testing, in vitro testing including simple bacterial screening and surveillance, animal efficacy studies and PK/PD studies through contract laboratories supported by NIAID. For these resources, which are offered free of charge to the investigator, you do not have to be an NIH investigator and it is not even clear that you have to be located in the US.  You do, I suppose, have to have something worth testing. For further information – check out this and related links -

Although this is more than laudable on the part of NIAID, there is a major problem here. Even though the NIAID says they support antibiotic research, a funding line of 6% (the payline for NIAID over the last year or so) means that they hardly fund any research at all.  Without the early basic research, we will never have products coming out of academia that might be eligible for the translational resources offered by NIAID.

On top of this, I am becoming extremely discouraged about the ability of our researchers to even enter the area of antibiotic discovery and preclinical development. I’ve spent some time over the last several months visiting academic centers and speaking with colleagues in academia on anti-infective research.  Although I am incredibly impressed with the level of motivation and the innovative approaches being taken in academia, I am equally impressed with the lack of real ability to understand what one can reasonably pursue and how to pursue it. There is also a lack of clinical understanding in many departments coupled with an absence of translational expertise that would allow projects to either move forward or be terminated (appropriately) early. In a situation where grant funding is extremely competitive like it is today, I fear for our ability to discover and develop needed new antibiotics in academia. 

When I think about those in academia today who actually have the skills necessary to discover new antibiotics and bring them forward, they are almost all that rare person who has left an industry career and gone into academia from there.  I can count these folks working on antibiotic discovery (that I know) on one hand.

But with the continuing demise of antibiotic discovery in pharmaceutical companies – both large and small – we desperately need this research to come from somewhere else.  Where?  Academia has to be part of the solution.  To this end, NIH must take a much more proactive role in getting our academic investigators appropriately trained in antibiotic discovery and development.  They have told me that they are doing this – but I personally see no evidence of it.

In addition, NIH must find a way to increase their funding for this research.  Of course, it makes no sense to fund investigators who are not capable of doing the work. So NIH must do both things.  They must fund training and work to assure that appropriately trained investigators get deserving projects funded.  This might mean that, for a change, antibiotics gets monies that might have otherwise been spent on HIV or HCV or vaccines or pathogenesis.  After all the years of NIH neglect, they certainly owe the American public, the world and antibiotics investigators this much.

Wednesday, May 1, 2013

Antimicrobial Resistance - the FDA Has Your Back!

I know you all will be excited to hear that the FDA has just added an informational release for consumers on “Fighting the Impact ofAntimicrobial Resistance.”  The best part of the piece is the photos of key FDA personalities.  The FDA explains how antibiotics transformed the health of Americans starting in 1940 (actually the revolution started with the sulfonamides in the mid-late 30s).  They then point out that some organisms have developed resistance to these important drugs.  They even point out that some organisms came already packaged with “intrinsic” resistance – presumably before the advent of antibiotics – but this is rather glossed over in this consumer info piece.

The message comes from both Ed Cox (above) of the office of antimicrobial products (human health) and David White (right) of the office for food and veterinary medicine.  Ed points out that the FDA is doing two main things to address antibiotic resistance. (1)  They are “facilitating” the development of new antibiotics with new recommendations providing for both practical and scientifically sound development pathways.  (2) They want to help assure the appropriate use of the agents we already have.  This is fascinating since all the guidance documents produced since 2006 with one exception specifically call for infeasible clinical trial designs for the development of new antibiotics. It is true that the FDA has been softening their approach within the last year and essentially are no longer following their own guidance documents – but all this is secret and behind closed doors.  Only those who actually speak to the FDA in confidence about specific products know that they no longer strictly follow their own guidance. But the message to consumers is a little misleading in that you get the impression that the FDA is a facilitator when for the last decade they have been quite the opposite. Europe has been leading the way here and it seems like the FDA is trying to follow – but its all still a secret.

On the veterinary side, David White (who should know better!), says that the FDA is approaching antibiotic use in animals using “voluntary” guidance.  That is, its OK for food producers in the US to continue to use low doses of antibiotics as food supplements to get their food animals to grow faster and therefore get to market faster.  They are encouraged to stop this practice in a voluntary way.  Right! That will work!  It is abundantly clear in study after study that antibiotic resistance is selected by these practices in food animals and that resistant organisms and the resistance genes they contain can be transmitted directly to humans or the resistance genes to human pathogens and that resistant human infections result from this process.  They do reassure us that most isolates from food-borne outbreaks are still susceptible to the first line drugs used to treat them – but what does that mean exactly?  I looked up the NARMS data for 2010 myself. There is extensive resistance to tetracycline, amoxicillin and augmentin but little resistance to Bactrim and ciprofloxacin among human, food and animal isolates of Salmonella. The FDA’s approach, in addition to “voluntary” guidance is to tell consumers to wash their food, their hands and their cooking surfaces and to cook the meat well – all good advice – but really!

On the basis of many years of evidence culminating with the superbug vancomycin-resistant Enterococcus (VRE), Europe banned the practice of using low dose antibiotics in food animals as growth promotants. Once again, the European regulators are leading the way while the FDA lags well behind.  Personally, I find it inexcusable that the FDA permits this practice to continue knowing the risk this poses to human health here in the US.  This is especially frustrating since the same FDA has obstructed new antibiotic development for years (although they have started to try and turn themselves around in the last year).

So – for you consumers out there – don’t worry – the FDA has your back!