David's New Book

Saturday, June 30, 2018

REVAMP - Its Here!!


And its called REVAMP (re-valuing antimicrobial products).  This bill, proposed in the US House of Representatives by Rep John Shimkus, R-Ind. and Rep Tony Cardenas, D-Calif. represents the most important advance in pull incentives since we began discussing them.  AND – its my preferred incentive – a transferable exclusivity voucher.  They express it differently – they call it an exclusivity conveyance but it adds up to the same thing. If a company gets an antibiotic approved and that new product addresses a priority medical need as determined by the CDC priority list, the company would receive up to 12 months additional exclusivity on that product. BUT – that additional exclusivity must be conveyed (transferred) to another product or products. It looks like the exclusivity could also be “conveyed” to other parties – “the holder of a conveyed exclusivity extension period may sell, exchange, convey, or hold for use, such period.” 

This incentive is extremely effective because it could be worth billions of dollars.  And, because it is transferrable between companies, it provides an incentive for investment in start-ups and biotech since large pharma will have a strong incentive to license any product that meets the CDC and HHS criteria.

There are a few conditions for the award –

§  Ensure availability of product for susceptibility device manufacturers
§  Identify, track and publicly report product resistance data and trends
§  Develop written guidelines and procedures for products appropriate use, which includes appropriate promotion practices, education, surveillance, monitoring and stewardship.
§  Develop education and communications strategies for health care professions about appropriate use
§  Submit a stewardship activity assessment to agency every two years 
§  Contribute five percent of the total value of consideration received from the conveyance to the Foundation for the National Institute of Health for early stage antimicrobial research.

The justification for the conveyance of exclusivity to products other than antibiotics is simple.  Many other therapies depend on our ability to treat infections.  Without this, the treatment of cancer, autoimmune disease including arthritis, and simple routine surgeries become much higher risk. The risk of wounds of war also would take us back to civil war days without effective antibiotics. 

The bill is limited to 10 such awards. After the fifth year post-enactment or the fifth award, whichever should come first, the GAO is to evaluate the effectiveness of the program for developing priority antimicrobials, and shall examine the indications, usage, development of resistance and overall societal value of the priority products that have received this award. 

It is impossible to judge how much this blog and your efforts contributed to this decision.  But I notice that the blog has received a large number of views from Washington and Arlington over the last several weeks.  That is very unusual and I suspect that congressional staffers are paying attention. 

Now, we must push our representatives in congress to vote for this bill! Please, once again, contact your representatives and express your strong support for this bill!  



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Friday, June 15, 2018

Gottlieb and FDA to the Rescue



This week, Scott Gottieb, our FDA Commissioner, stated that he was examining, along with the Center for Medicare and Medicaid Services (CMS), a possible pull incentive for antibiotics. Specifically, he said, “It is my belief that a licensing model might offer an effective 'pull incentive' that attempts to create a predictable market for antimicrobial drugs that would meet a narrow set of critical, public health criteria.” The idea of licensing instead of paying per dose (as is done currently) would be to license the ability to use the drug for a period of time for a fixed fee. In this case, CMS would pay the license fee. This is one of several models for pull incentives that have been discussed at DRIVE-AB and in other forums. It is not my favorite. But this is remarkable in that someone at this level in this administration is even proposing any pull incentive at all. Of course, because this is CMS, the license would theoretically only cover Medicare and Medicaid recipients. So those of you not covered would still have to get say colistin for your resistant infections (LOL!).



Over 10 years ago, I worked with Dr. Gottlieb on a task force convened by the Manhattan Institute. We worked on using biomarkers and other methods to allow for regulatory approval of needed new medications prior to the time pivotal clinical data might be available. I tried to introduce such a mechanism for antibacterials and antifungals, but the absence of biomarkers for these infections made this a challenge. Our task force may have contributed to FDAs thinking about oncology and perhaps antivirals, however. My work with Dr. Gottlieb convinced me that he shared the frustrations of those working in the antibacterial area that regulatory requirements at the time were too stringent or too uncertain to sustain investment in research. Now that he is FDA’s Commissioner, I’m sure he remembers those discussions and I’m sure he has been following all of our debates around resistance, regulatory pathways and monetary incentives.



On the same front, FDA just released its Draft Guidance for the development of antibacterial and antifungal drugs for limited populations of patients with serious or life threatening conditions or LPAD. While this is a step forward in that it formalizes the existence of such a pathway, the requirements for approval have not changed beyond what has been previously stated by the FDA in their unmet needs guidance and elsewhere.



Nevertheless, Gottlieb’s statement and the LPAD draft guidance are potentially important steps in the fight against antibiotic resistance. To make these steps come to fruition, we need action. We need a clear and above all feasible regulatory pathway forward for studying infections in small populations of patients. We also need significant pull incentives now to fix the broken antibiotic marketplace.





Monday, June 11, 2018

REVIVE: open access to knowledge and resources for the antimicrobial R&D community

GUEST BLOGGERLaura Piddock - Head of Scientific Affairs, Global Research and Development Partnership (GARDP).


webinar June 13!!!


The sulphonamide drugs were first used in patients in the 1930s; this was closely followed by the development of penicillin and the ‘golden age’ of antibiotic discovery. Today, it is a very different situation with few new treatments but increasing numbers of difficult to treat drug-resistant infections. The void in discovery and development of antimicrobial drugs over the last 20 years leaves us facing a future where once treatable infections are becoming life-threatening. 

The discovery void has also created a vacuum in the experience and knowledge of researchers working on antimicrobial research and development (R&D). As an optimist, one of the exciting things I see in my role as Head of Scientific Affairs at GARDP, and Professor of Microbiology at the University of Birmingham, is the promising projects in small to medium sized biotechnology companies and academic research groups who are working to fill the gap in new antimicrobials. One of the things that attracted me to join GARDP is applying my clinical microbiology and research experience to discovery, R&D of new treatments for multi-drug resistant infections. Through GARDP’s Antimicrobial Memory Recovery and Exploratory Programme (AMREP), we aim to recover the knowledge, data, and assets of forgotten, abandoned, or withdrawn antibiotics, and to identify new treatments.

A key element of AMREP is the creation of REVIVE – an online space where researchers can share knowledge and connect with each other. I’ve been lucky enough in my career to be surrounded by, or at least have relatively, easy access to experts I can call upon for advice and support. Ironically, while technology can better connect us today, working in a research field with a steadily decreasing number of experts, can leave researchers new to antimicrobial R&D isolated. 

That’s why we’ve invited seasoned, internationally recognised experts to be part of REVIVE’s ‘match-making’ facility – supporting exchange between early career researchers and those now refocusing their research to address the AMR crisis, whether they be clinical and non-clinical researchers, with world-class experts in antimicrobial R&D. The aim is to improve, accelerate, and streamline antimicrobial drug discovery, R&D by connecting researchers directly with retired and established antimicrobial researchers and developers. 

We’re also connecting people through our webinar series – the first of which is on Wednesday 13 June. I’m delighted David Shlaes is able to join us live to share his extensive knowledge and experience on clinical development for non-developers and focus on traditional development (tiers A and B). This is the first in a series of three webinars with the following sessions discussing development of antibacterial drugs targeting specific pathogens and development of antibacterial drug enhancer combinations. If you’re not able to join us live, all our webinars will be available for you to watch free of charge on REVIVE

In addition to webinars, we’ve co-organized sessions with CARB-X at the recent ECCMID and ASM Microbe conferences. We’re also making these available on REVIVE as not everyone has the time or funding to attend these conferences. Moreover, we’re hoping to recreate part of the ‘attending conference experience’ by organizing follow-up live Q&A webinars for some of these presentations. 

As a researcher in an established academic institution, I am fortunate to have access to most scientific and medical publications. However, this is not the case for the many working in antibiotic R&D – but access to these is critical to keep our knowledge current and challenge our own thinking. With this in mind, the focus of building REVIVE’s resource library is to signpost you to free, open-access resources on antimicrobial drug discovery and development. 

GARDP’s vision through REVIVE is to give the antimicrobial R&D community a space to interact and learn from each other. We want to work with the community and grow REVIVE into a resource that meets your needs. I encourage you to explore REVIVE and send us your feedback.

I look forward to you joining us on 13 June for our webinar.







Wednesday, June 6, 2018

Urgent - Time to Act!

For those of you who have not been following this story closely, the market entry rewards we have been discussing that are intended to fix the broken antibiotics market are not currently part of the Pandemic and All-Hazards Preparedness Reauthorization Act.  This legislation was our best hope of getting something in the budget. I have it on good authority that we should write the following congressional representatives in this regard. 

Rep. Doris Matsui (D-CA) megan.herber@mail.house.gov
Rep. Anna Eshoo (D-CA) rachel.fybel@mail.house.gov
Rep. Brett Guthrie (R-KY) sophie.trainor@mail.house.gov
Rep. Chris Collins (R-NY) charlotte.pineda@mail.house.gov
Rep. Marsha Blackburn (R-TN) meghan.stringer@mail.house.gov

Some talking points for you are included below. 

The antibiotic market is broken. The problem, from the private market view, will not be addressed anytime soon.  

In the meantime, antibiotic resistance is not going away.  The CDC estimates that we lose 23,000 American lives every year and $20 billion in excess costs to the problem of resistance.  Most experts, myself included, believe this is a vast underestimate. The O’Neill commission in the UK estimates that globally we lose 700,000 lives a year today to resistance.  They noted that if current trends continue, we will see over 10 million deaths and one hundred trillion dollars in lost GDP globally by 2050.  Ultimately, we will end up in a world where simple surgery, cancer chemotherapy, wounds of war and routine medical treatment will become dangerous because of the lack of antibiotics available to treat common but resistant infections.

At the same time, investment in antibiotic research and development is at an all time low. Between 2000 and 2010 all but a few large pharmaceutical companies had jettisoned their antibiotic research efforts. In recent years, Astrazeneca, Sanofi, and J&J all followed suit. The Medicines Company and Allergan disinvested within the last year and more companies are likely to follow soon. This is mainly due to lack of market incentive to pursue antibiotic research. Private investors have heard this message and consequently private funding of biotech is in danger as well. 

Even though public funding of antibiotic research has increased, there is no way to bring any resulting products to market without the participation of the private markets. 

To solve this impasse, government must act. The GAIN act did not work because extending exclusivity on a non-profitable product is not an incentive. Some sort of market entry reward is required to fix the broken antibiotic marketplace and re-incentivize private investment in antibiotic research. Most experts estimate the cost of this to the US would be something like $20 billion over ten years.  The consequence of not acting is too horrible to contemplate. 

I am happy to discuss this with you or your staff at any time.  Other experts you can contact include Kevin Outterson, John Rex and David Shlaes. 





Friday, June 1, 2018

Allergan Bails!

NEW FLASH!



I hate being right when it comes to pharmaceutical companies abandoning antibiotic R&D.  But Allergan just announced that they are putting their infectious diseases unit up for sale as I predicted might happen back last November. They seem to be concerned about their falling stock price according to the Reuters report. But finding a buyer at the right price in the current market atmosphere is not going to be easy.  The most logical customer would be Pfizer since they own the rest of world rights to Allergan’s North American antibiotics Teflaro and Avycaz. But rumors suggest that Pfizer is not happy with the antibiotics market either. 

Once again we will have antibiotic developers retiring, unemployed or working in other therapeutic areas. Once again, the world of potential investors in antibiotics will be shivering in their closets. 

Until governments take concrete steps to shore up the failing antibiotics marketplace, we will continue to see companies abandon the area.  We may see biotechs fail simply because they are unable to garner the private investment they need or have no buyers for the products in development. 

With every incident such as this one, we take another step closer to that post-antibiotic era that we all dread so much.