ANTIBIOTIC MARKETS AND SPLU - GUEST BLOGGER – LEW BARRETT

Logo of the . (Photo credit: Wikipedia)

The Neonatal Intensive Care Unit. (Photo credit: Wikipedia)

Lew Barrett is an old friend and colleague of mine from Wyeth.  He was the VP of US Infectious Diseases Marketing when I was there and as such we worked together closely for a number of years. Lew then assumed the role of VP US Marketing and Global Business Manager Infectious Diseases at Wyeth. Lew was, in large part, responsible for the surge in Pip-tazo sales to over $1B.  I asked Lew to help us understand the market implications for the Special Population, Limited Use (SPLU) proposal of the Infectious Diseases Society of America.

I thank David Shlaes for the invitation to share my thoughts regarding the commercial viability of anti-infective drug development in light of recent discussions and pronouncements at FDA and in Congress.  Lots of acronyms, Bills and ideas have been submitted recently in the U.S. to stimulate drug development and approvals: GAIN, SPLUs FAST and TREAT just to name a few. 

Most recently, the concept of SPLU approvals has been discussed.   The hope is that trial design, numbers of patients and time might be reduced.  The approved uses: narrow and limited.  One wonders however how small is small and how fast is fast.  In a paper recently published in Clinical Infectious Diseases [Vol. 54, No. 5, 1 March 2012, Linezolid was compared with vancomycin for the treatment of MRSA nosocomial pneumonia.  The study took over 5 years to complete.  1225 patients were randomized to study 448 MRSA pneumonia patients.  Finding resistant pathogens in clinical studies is tough!  Can I say rapid bedside diagnostics?

So assuming a SPLU’s come to pass what are they worth?  Professional forecasters beware, I am conducting a rough and dirty analysis, but directionally I think it makes sense.

Data Sources:  1.  Decision Resources has published several syndicated studies over the last year.  Their data provides us useful epidemiology insights.  Thanks to several colleagues for help with this information.  2.  T.E.S.T. (Tigecycline Evaluation and Surveillance Trial) http://testsurveillance.com/ is a global multi-center surveillance study designed to assess the in vitro activity of tigecycline and comparators against a range of important pathogens.  Thanks to IHMA and the TEST team for fact checking my analysis.  I used Decision Resources to provide patient numbers, T.E.S.T. to identify % MDR.

My example:

SPLU drug approved for MDR Acinetobacter in the U.S.¹

Infection	Number of US Patients infected with Acinetobacter
HealthCare Assoc. pneumonia	18,500
Nosocomial pneumonia	11,900
Ventilator-Assoc. pneumonia	13,900
UTI	36,500
Blood stream infection	12,000
Complicated skin+Surgical Site infection	202,200
Total Acinetobacter patients	295,000

295,000 Acinetobacter spp. patients.  How many fit the SPLU definition?  Using T.E.S.T.², I calculated the number of MDR Acinetobacter.  My definition:  any isolate resistant to at least 3 classes of antibiotics.  I used:  3G/4G cephalosporins, carbapenems, fluoroquinolones, beta-lactam/beta-lactamase inhibitors and aminoglycosides.  Unfortunately neither colistin nor tigecycline is evaluated.  Colistin because it was not tested, tigecycline because TEST is a Pfizer study and tigecycline is not indicated for nor has any breakpoints for Acinetobacter .  This is a limitation of the analysis. 

I limited Acinetobacter to strains isolated from the urine/bladder, lung, complicated skin/surgical sites, and blood in an attempt to mimic the Decision Resources data.

35% of U.S. Acinetobacter were resistant to at least 3-classes of antibiotics.  

SPLU defined Acinetobacter patients:  103,000 (295,000x32%).

Assuming 100% market share of 103,000 patients for our new drug (not happening):

$100/day x 14 days = $1,400 course of therapy:  $144MM

$350/day x 14 days = $4,900 course of therapy:  $505MM

$700/day x 14 days = $9,800 course of therapy:  $1.0BWhat share of patients is likely?  The limited indication itself, stewardship programs, ID restrictions will all reduce share.  Colistin, tigecycline, combinations of agents and other new drugs (I hope) will also reduce share.  I leave it to each reader to decide what is appropriate, however a generous 50% market share reduces the annual revenue stream to between $72 and $500 million dollars. 

What about a more prevalent pathogen you may ask.  By comparison, 524,000 Pseudomonas aeruginosa infected patients were reported by Decision Resources.  The MDR rate, per T.E.S.T. is 10%.  So we are talking about even fewer MDR P aeruginosa patients, 54,000.    

What about spillover sales or off-label sales.  My personal belief is that price, stewardship programs, formulary restrictions, the label itself and external oversight will limit extraneous use.  Oversight from payors on the hospital side and the government on industry’s side, especially for a new regulatory approval process, is likely.   HHS, OIG, and federal and state attorneys general have been scrutinizing manufacturer’s commercial activities.  One only has to look at fines assessed against Forest, Pfizer, most recently J&J,  and others for marketing activities to verify my point.  J&J’s fines for marketing activities are in the final stages of negotiation. 

Lastly, what happens when an SPLU approval is broadened based on required post-approval studies?  If no new agents are approved to treat the original MDR problem, I suspect that formularies will keep the clamps on use, regardless of any price changes by the manufacturer.  So if the use is going to be constrained I suspect that the price will remain high.  

In summary, SPLU approvals appear intriguing. I believe that SPLU qualifying antibiotics will need oncology-like pricing to be attractive to any sponsor; small pharma, VCs or big-Pharma. If combined with extensions to exclusivity and/or tax credits even more so.  But, SPLU approvals may be more attractive to small or start-up companies versus big pharma.  Big Pharma still has the issue of resource allocation across various projects; a faster, limited approval may not meet the threshold for investment in the big pharma portfolios.

1.    Decision Resources:  Hospital Treated Infections, November 2011.

2.    T.E.S.T.  Tigecycline Evaluation and Surveillance Trial.  Data run 16March2012.

Lewis Barrett, President & Owner

LLBarrett Biopharmaceutical Consulting, LLC

LLBarrett3@Verizon.Net

LinkedIn:  http://www.linkedin.com/pub/lew-barrett/10/b68/833

LL Barrett Biopharmaceutical Consulting provides strategic consultation to the global life sciences field with a particular focus on brand strategy (positioning, differentiation, global branding and access); lifecycle strategy, business development, and strategic communications. Mr. Barrett has a breadth and depth of experience in the anti-infective, hospital and biopharma fields.

The Infectious Diseases Society Steps Up!

Image via Wikipedia

Yesterday was a big day for news on the antibiotics front.  The Infectious Diseases Society of America (IDSA) presented testimony to support reauthorization of the Prescription Drug User Fee Act (PDUFA) whereby certain incentives for antibiotic R&D would be included.  Their testimony and press release are provided here by links.

To me, by far, the most important aspect of their testimony and the subject of the press release is FDA reform.  They clearly point out, in no uncertain terms, that the lack of feasible trial designs to meet FDA requirements is undermining our ability to bring forward new and needed antibiotics.  The entire quote from this section of the IDSA testimony is shown below.

One solution proposed by IDSA is a good one, but one that, in my view, will still have very limited applicability to expanding our antibiotic pipeline.  They propose a pathway they call “Special Population, Limited Use (SPLU).”  This hearkens back to Mark Goldberger’s 2002 call for trials showing high quality but low quantity. In fact, this idea has been discussed both within and outside the FDA for at least the last decade.  It would involve invoking subparts E and/or H of the FDA regulations to allow exactly this – approval of drugs targeting limited populations with high medical need.  In the case of antibiotics, this would be those patients with serious infections caused by pathogens resistant to either all approved antibiotics or all but two last line agents such as say tigecycline and colistin - where we don’t know that either will work in such infections anyway.  These antibiotics would be restricted to very limited use only in those targeted populations.  A high price could assure that there would not be much off-label use. 

The advantage of the IDSA initiative is that it gets the FDA talking seriously about this approach – something they have failed to do since Mark Goldberger.  Another very positive aspect is that it may provide a pathway for some new antibiotics.  I can only think of two possible candidates for this approach today.  One is the Pseudomonas-specific antibacterial peptide from Polyphor.  A second would be if some company ever decided to develop a combination of a monobactam plus a beta-lactamase inhibitor similar to avibactam that could be used to treat infections with most metallo-beta-lactamase producing organisms including NDM-1.

Even for these examples – the devil will be in the details. 

Here is what Janet Woodcock said – “A company might be able to test a product on 400 patients rather than 8,000 to get it on the market. But it could only be used for a very limited group of patients with life-threatening antibiotic-resistant infections for which other medications are not available, not widely for off-label uses.”  But of course no antibiotic is ever studied in 8000 patients to begin with (or almost never) and enrolling 400 patients with serious infections with MBL-producing strains will be next to impossible in any kind of reasonable time frame.  Other questions include that of the indication.  Can one enroll patients with infections at any site including the urinary tract?  Will UTI patients be excluded?  Is it OK to lump skin and soft tissue infections with pneumonia as might be required to study patients with Acinetobacter infection?  Is mortality the endpoint or is it cure (I believe mortality will be very challenging and highly confounded as an endpoint).

For other antibiotics with broader spectrum or targeting more general populations will this “new” pathway allow for more rapid entry to market?  I’m not sure.  For example, is it much faster to develop it for these rare infections and get an early approval, begin to accrue revenues and then study the drug for a broader indicaton?  In that case, you would start out at a very high price then lose both your pricing advantage and the SPLU designation after approval for a more traditional indication like UTI or intra-abdominal infection for example. I am not convinced that the timelines fit here and that this makes any sense - hence my belief that SPLU will benefit a very small number of drugs.

 Another aspect yet to be determined is the NPV for the companies for an SPLU drug.  Clearly the price could be high, but will the number of patients treated provide a return on investment under these circumstances?  I would need the help of a marketing person to sort this out and I will seek such help and provide a follow-up to this blog soon.  At the end of the day – large pharma may be willing to forgo profits for an SPLU antibiotic.

In conclusion – this is an important initiative by the IDSA. I am skeptical that the FDA will be able to make even this key initiative feasible on planet earth. I believe that if the FDA can make this approach feasible, it will only benefit a very few new antibiotics – but that would still be a very positive step. Finally, I think the jury is out on return on investment – but this may be less important to large pharma in this case. 

Related articles

• Approving Antibiotics - IDSA Submits Proposal (medicalnewstoday.com)

Antibiotics, FDA and PDUFA

Image via Wikipedia

The Prescription Drug User Fee Act (fondly known as PDUFA) is apparently up for renewal by our do-nothing congress.  This act, created in 1992, was designed to provide FDA funding from sponsors to accelerate the review process for drug approval applications by allowing the FDA to hire additional personnel and to acquire other necessary resources. The Infectious Diseases Society of America has led a charge that now includes 50 other societies to support the passage of PDUFA while insuring that incentives are provided for anti-infective therapeutic and diagnostic R&D.  But their letter is so tepid and vague as to be unclear as to their goals for congress other than including consideration of antibiotic and diagnostic R&D in reauthorization of PDUFA.  Our top 10 goals should be regulatory reform at the FDA such that the FDA is prohibited from requiring clinically or logistically infeasible designs in draft guidance documents.  The guidances for virtually every indication that have emerged since 2003 fit this description and include the following indications – acute otitis media, acute bacterial sinusitis, acute bacterial exacerbations of COPD, community acquired bacteria pneumonia (CABP), hospital acquired and ventilator associated pneumonia, and, most recently, complicated urinary tract infection.  The guidance for acute bacterial skin and skin structure infection trials requires designs that are feasible but with endpoints that are clinically irrelevant.  The CABP guidance is both infeasible and irrelevant. In the case of the so called mild, self limited infections like AOM, ABS and ABECOPD – no one has even discussed these with FDA as far as I know and there are certainly no new antibiotics being studied in these indications. The CABP guidance is now in its fifth year of discussion and we still don’t have a feasible way forward. Hospital acquired pneumonia is our area of greatest medical need and that guidance is completely infeasible.

The FDA has taken to issuing draft guidance documents and then waiting for the world to explode with critical commentary before getting around to the real business of feasibility.  This re-evaluation then takes years to complete.   This has got to stop. 

I am now thoroughly convinced that the FDA’s perseveration around non-inferiority trial design has nothing at all to do with science – either regulatory (whatever that is) or otherwise.  It is entirely based on politics.  They fear another Ketek scandal and investigations by folks like Grassley and Markey. Tom Fleming is probably still on the advisory committee because of his links to these congressmen.

So – I would ask the IDSA to send a different letter.  It should ask congress to withhold PDUFA authorization until the anti-infectives group at the FDA is reformed such that they would be required to have draft guidance documents reviewed for feasibility before release by people who know what they are doing in this regard.  This requirement would clearly let most of the folks on the FDA staff and even the AIDAC out of the picture.  An independent group would be necessary for such vetting.

Such regulatory reform is THE ONLY way forward.  No incentives in the world will help our pipeline if there is no regulatory way to approval for new antibiotics.

Related articles

• PDUFA critical for innovation and patients (thehill.com)

Groundhog Day - Urinary Tract Infection at the FDA

Cover via Amazon

Image via Wikipedia

Its Groundhog Day at the FDA!  Urinary tract infections and intraabdominal infections are key indications allowing entry into the therapy of Gram-negative infections – our area of highest medical need currently and for the foreseeable future. In spite of multiple conversations and blogs exhorting the agency not to release guidance documents for complicated urinary tract infection and complicated intraabdomninal infection before their ideas can be vetted for their feasibility in the real world, the FDA has done just that.  Yesterday, their new Draft Guidance - Complicated Urinary Tract Infections: Developing Drugs for Treatment - was published.  Once again, it is detailed and comes with a detailed appendix to calculate a required non-inferiority margin of – guess what – 10%.  

But lets take things one at a time.  As is often the case, there are some good things in this guidance.  These include the willingness of the FDA to discuss superiority designs that seem reasonable for those patients with “unmet need” – that is those suffering from infections caused by multiply-resistant or pan-resistant pathogens where the new therapy offers the possibility of cure.  They offer several design suggestions and note that they are open to discussion on other approaches.  Yaayyy!!!

Another positive aspect of the guidance is the recognition that IV therapy for the duration of total dosing (usually 10-14 days) will be impossible.  They allow for the continuation of therapy as an oral drug other than the investigational drug or its comparator for a period of time. This will be essential for the study of IV drugs for which no oral formulation is available.   They do want an evaluation for clinical and microbiological response at the end of IV therapy as well as clear criteria for the switch to oral therapy – OK.

They also encourage sponsors to study shorter durations of therapy – consistent with current clinical practice.  Bravo.

The inclusion and exclusion criteria they suggest seem reasonable except for one key item.  And now the fun starts.  They preclude any previous antibiotic therapy for the 48 hours preceding entry into the trial with a drug that has activity in the treatment of urinary tract infection. In the face of a positive urine culture at the time of entry, or perhaps better, a positive urine culture with an organism resistant to the antibiotic used previously. This stance will rule out the entry of the vast majority of patients with cUTI both in the US and the rest of the developed world.  Once again, one might question the ethics of withholding therapy for a patient with pyelonephritis who is suffering from pain, fever and possibly has bacteremia while they wait for all the procedures required to get them enrolled into a trial so they can start therapy. This issue was raised during the discussion of community acquired pneumonia at the last FDA advisory committee meeting – but apparently, the agency has been unable to extrapolate that message to UTI.

The other major issue with the guidance, once again, is the magical NI margin of 10%.  It is amazing that no matter how extensive the treatment effect is for a given infection, we always end up with a margin of 10%. In its extensive appendix, which must have taken a team of people many months to assemble at the FDA, the agency goes through their justification for a 10% margin.   Here we’re back to the preantibiotic era publications.  These involved very small numbers of patients where, frequently, the organism was called the colon bacillus.  We presume that is E. coli – but who knows? Their review suggests that an average of 26% had spontaneous resolution of symptoms and microbiological clearance without specific therapy.  They then go through a number of recent trials for cUTI demonstrating a 73% average clinical plus microbiological success rate.  I get that that results in a 47% treatment effect.  Next, they look at clinical and microbiological success at End of Treatment – or on day 5 of therapy.  In the FDA’s view – not an unreasonable one really – an assessment at the end of IV therapy is required if you are going to switch to an oral antibiotic different from the investigational drug or comparator as would be the case for an IV drug with no oral formulation available. That gets you down to a 69% clinical and microbiological response rate – for a treatment effect that is still 43%.  But then, once again, the FDA performs its discounting magic. Based on taking the lower bound of the 95% confidence interval and via other discounting measures, the 43% suddenly becomes 23%. That gets us to a justified NI margin of 10%.  Isn’t that convenient? My view of this is that it would be easy to justify a 15-20% NI based on the data they presented. 

The FDA then goes on to provide trial size calculations for us.  Based on 90% for each of two trials, and assuming an 80% microbiological evaluable rate, they calculate that 495 patients are required per arm for an astounding 1000 patients per trial.  A total of two trials are required giving us 2000 patients enrolled. 

These two provisions, the proscription against any prior antibiotic and the 10% NI margin on the microbiologically evaluable population once again render the design totally infeasible and possibly even unethical. I have personally studied two IV drugs that had no oral formulation in cUTI.  The most recent was Novexel’s, now Astra-Zeneca’s ceftazidime-avibactam.  In our phase II trial in cUTI, we allowed a single dose of an active antibiotic within 48 hours of enrollment. Our microbiological evaluable rate was 45%. These numbers gives me 1604 patients per trial or 3200 patients for two trials.

I can tell you that running a trial in cUTI with an IV only drug and requiring 5 days of IV therapy is an unbelievable challenge and won’t happen here in the US.  In our most recent such phase II trial, we went to Guatemala, India, Jordan and Lebanon to enroll patients.

So – FDA – can we start over?  I hope you are not actually requiring companies to comply with this guidance.  If you are – good luck to those folks!

Antibiotic Breakpoints, FDA, CLSI, EUCAST etc.

One of the most important issues in the development and marketing of a new antibiotic is the breakpoint that is ultimately assigned by the regulatory authorities.  For the uninitiated out there, this is the way clinical laboratories determine whether a given bacterial pathogen identified in some clinical specimen (urine, blood, sputum, etc) is actually susceptible to an antibiotic or not.  This determines whether the antibiotic is likely to work for a given patient’s specific infection.  It also determines, for each pathogen, how many such infections will be “covered” by the new antibiotic and therefore how useful it might be for physicians and their patients suffering from infections caused by that pathogen.  It makes no sense, for example, to study an antibiotic for infections where only 50% of those infected are likely to be covered unless no other antibiotic covers the infection at all.

So – how does this work?  Each pathogen is assigned a breakpoint corresponding to susceptible or resistant (and sometimes intermediate) for a given susceptibility testing method – and there are a few out there.  Mainly it is a zone of inhibition of growth of the bacteria around a disk placed on an agar plate.  It may also be inhibition of growth in panels containing wells where the antibiotic is diluted stepwise. The level at which the cutoffs for inhibition zones or for concentrations that inhibit growth correspond to susceptible are determined by the regulatory authorities – the FDA for the US and EMA for Europe - mainly.  How do they do this?

For the most part, the regulatory authorities rely on the susceptibility of organisms studied in the clinical trials provided by the sponsor.  For example, if you determine that all the staph strains in the world are inhibited by your antibiotic at a concentration of 10 micrograms per ml, if your clinical trial only enrolls patients whose staph strains are all inhibited at 1 ug per ml, your susceptibility breakpoint will be 1 ug/ml assuming that these patients were actually cured in your trial. That means, even though your antibiotic may actually work against strains with much greater levels of resistance, no one will use it to treat such strains since they will be labeled by the microbiology laboratory as resistant based on the cutoffs assigned by the regulatory authorities.

Of course, because we know so much about how antibiotics work based on animal models and based on modeling of how the antibiotic works in people, we can frequently predict with great accuracy that we can actually predict that patients with pathogens requiring 10 ug/ml of antibiotic to inhibit growth would actually be cured in clinical trials.  But – if you haven’t shown this, it is very hard to get the regulators to agree that this is a reasonable cutoff.

This is a terribly important point since it might mean the difference between being able to market your drug to 50% of patients with a given infection or 90%. But it amazes me that we really pay so little attention to this in the early days of developing a new antibiotic.  We need to consider how to get patients likely to have organisms with higher levels of resistance into trials (both for the comparator and for the new drug) to justify higher breakpoints.  But the regulatory authorities need to pay more attention to our predictive powers using pharmacometrics to help establish higher breakpoints than might be justified by the patients re3cruited into our trials.  Although both Europe and the US pay lip service to this concept, it is practiced more in the breach than the observance.

Complicating the picture further are the roles played by the Clinical Laboratory Standards Institute in the US and EUCAST in Europe.  EUCAST analyzes all the relevant information and makes a determination of both a breakpoint to be used in epidemiological reporting – to survey for emerging resistance – and a separate breakpoint for clinical therapy.  The EUCAST breakpoints become the breakpoints for the EMA in Europe.  In the US, the situation is more complicated – or maybe less so depending on your point of view.  The Clinical Laboratory Standards Institute (CLSI) determines breakpoints for susceptibility, but these have, in a way, little meaning since the only breakpoints the manufacturers can use are those provided by the FDA. If a given hospital or laboratory wants to alter their breakpoints, for those antibiotics and pathogens where the FDA and CLSI disagree, they must do so on their own responsibility.  But as long as the device allows for this to happen, the individual hospitals or laboratories can initiate this change.

Finally, when I asked one of the testing device manufacturers whether they had any skin in this game, the response was, “no.”  They will sell their devices and kits regardless of FDA, CLSI, EUCAST and EMA pronouncements on breakpoints or even regardless of whether a new antibiotic is approved or not or whether the new antibiotic is used or not.

I will follow this up with more details on specific EUCAST, FDA and CLSI viewpoints in future blogs. In the meantime – I hope you are all as confused as I am. 

Speaking of Antibiotic Task Forces

In my last blog I reviewed a number of committees and taskforces on antibiotics and antibiotic resistance in which I have participated in one way or another.  But one that I left out is the Antimicrobial Availability Taskforce (AATF) of the Infectious Diseases Society of America (IDSA).  The IDSA (and its sister societies) is probably the most prestigious and well-respected group in the world when it comes to infectious diseases.  A number of years ago, they began to take a keen interest in the declining antibiotic pipeline, its potentially catastrophic implications for patients and physicians and the role of the US as a society and our regulatory agency, the FDA, in this emerging public health threat.  In response to this, the IDSA put together this task force which included a number of experts from a variety of different disciplines from antibiotic discovery scientists to practicing clinicians to clinical trial and regulatory experts. They asked me to participate as well.  At the time, I was becoming frustrated with the Forum on Emerging Infections of the Institute of Medicine (IOM) because I felt that in spite of all our work and our various publications, we were not able to push requisite changes at any level.  IDSA is able to lobby congress while the IOM cannot. I immediately left the Forum of the IOM and joined the IDSA effort.  The immediate result of this effort was the now well-known white paper, Bad Bugs, No Drugs that was released in 2004.  I am very proud of this paper and the Society for bringing this issue into the public eye with greater force than anyone previously.

With this white paper, the IDSA embarked on a campaign to bring about the changes necessary to improve our pipeline.  They carefully update their pipeline assessment and note their progress every year.  Since 2004, they have worked hard on all relevant fronts in this battle.  They push for antimicrobial stewardship in every health care setting, they have an initiative on limiting unnecessary use of antibiotics in agriculture, they provide information on resistance in the US, and they have initiated a campaign they call 10 x 20.  The 10x20 campaign challenges the world to come up with 10 new antibiotics active against resistant bacteria by 2020.  (I actually believe that we will achieve this goal, although probably not in the US unless something drastically changes at FDA). 

The AATF of the IDSA has really focused on two key areas to achieve their goal.  One is regulatory reform at the FDA and the other is incentives for industry through legislative efforts. And I believe they have been effective on both fronts.  The FDA is slowly beginning to see that releasing guidance documents requiring infeasible designs only takes us backwards.  The IDSA has been essential in getting the FDA as far as they have come – but we are still a long way from where we need to be.  They have accomplished this through a series of public workshops with FDA and with many meetings both in person and over the telephone.  They have also been instrumental in participating and leading the Foundation for the National Institute of Health Biomarkers Consortium effort to help the FDA at least define feasible endpoints for their new trial designs. Once again – the question is why are we stuck with these endpoints anyway and why can’t we define feasible non-inferiority margins for infectious disease indications.

On the incentives side, I think the IDSA can take much credit for the GAIN act that is shuffling through congress.  The problem is that I don’t think the GAIN act will actually incentivize the companies that we need to target with incentives.  And, personally, I am now questioning whether the markets in emerging economies will not provide enough of an incentive without government intervention.  Nevertheless, that the IDSA has come as far as they have is an accomplishment that we all have to recognize with gratitude.

So, even though I don’t always (infrequently?) agree with the specific directions the IDSA takes, and even though I remain frustrated with the amount of time this is all taking, the IDSA deserves many kudos and much recognition for what they are doing.  My advice to the IDSA on the regulatory front – where I think they can make the most impact – is – get aggressive!  No more Mr/Ms nice guy!

Another Taskforce Bites the Dust!

Cover via Amazon

Cover via Amazon

I don’t know how I missed this, but the Transatlantic Taskforce on Antimicrobial Resistance published its long-awaited report in September last year.  I was disappointed but not surprised.  I have been involved in a number of such efforts going back to the mid-1980s.  Back then a number of us engaged in research on antimicrobial resistance began to suscpect that there was an active bias against funding such research within NIH.  We carried out an investigation of the previous 25 years or so of funding and found that the record of NIH funding for such research was absolutely appalling.  We suggested as a key step forward that the NIH establish a new study section peopled with experts capable of reviewing grant applications in this area.  In 2006, 20 years after our original suggestion, they did just that.  And that was the most successful such effort in which I have participated.

In the early 1990s, the US government established an interagency taskforce on antimicrobial resistance.  I was a member of the first group of advisors for this taskforce.  At the time, I was very concerned about the US research agenda.  Virtually all of the recommendations from our section were ignored.

In 1994, the ASM convened a similar taskforce in which I also participated.  This report called for more funding for surveillance and for more research to better understand the role of antibiotics used in farming and aquaculture.  While some of the recommendations were followed to one extent or another, basic research on antimicrobial resistance in the US still had to await the formation of the new study section for the NIH in 2006.

For seven years I participated in the Forum on Emerging Infections at the national Academy of Science led by Josh Lederberg following his landmark book on emerging infections.  During those years, I tried to focus on the impending disaster in our antibiotic pipeline.  1999 saw the first of the large pharmaceutical companies to abandon the area of antibiotic R&D and the continuing consolidation with the industry was also taking its toll.  My own focus became more and more the regulatory environment in the US.  In 2001, an entire chapter in the Forum’s report on Biological Threats and Terrorism was devoted to this topic. And where are we with US regulation for antibiotics and biothreats today?

The report from the transatlantic taskforce is disappointing but for a different reason.  It’s recommendations regarding strategies for improving the pipeline aside from the discussion on incentives are so weak as to be inconsequential.  With a report like this, we are going nowhere. The key recommendations from improving the pipeline are as follows:

Incentives to stimulate the development of new antibacterial drugs in human medicine	Policymakers should strongly consider the establishment of significant incentives to stimulate antibacterial drug development
Research to support the development of new antibacterials	Increase communication between US and EU research agencies to identify common scientific challenges that may represent opportunities for collaboration
Publicise funding opportunities to EU, US research communities
Regulatory approaches for antibacterial products	FDA and EMA intend to discuss ways to facilitate the use of the same clinical development programme to satisfy regulatory submissions to both Agencies
Establish regular meetings between FDA and EMA to discuss common issues in antibacterial drug development and regulation
Exchange information on possible approaches to drug development for bacterial diseases where limited drugs are available

For the FDA and EMA to exchange information and establish regular meetings – come one!  What outcomes are desired from these exchanges that will impact our pipeline?

I’m sorry – but I guess my expectations for this taskforce, as low as they were, were still too high.