Wednesday, July 19, 2017

Antibiotics - Incentives Meet Reality

There are many important developments occurring on the antibiotics front. Progress in regulation, especially by the FDA, continues. Push incentives are gaining even more steam. GARDP recently announced an agreement to pursue a novel therapy for Neisseria gonorrhea infection. But I am staying focused like a laser on the issue of pull incentives because I consider this our greatest and most urgent challenge.

Recent data suggests that recently approved antibiotics are not earning anything like the kind of revenues that new products in other domains such as neuroscience (multiple sclerosis, Alzheimer’s) or oncology currently garner. $80 million per year seems good for these new antibiotics. According to the Boston Consulting Group's report for the GUARD initiative, for recent antibiotic launches, the net present value projected over 10 years is estimated at minus $500 to minus $100 million.  This compares to minus $450 million to plus $8.2 billion for recently launched oncology products. Obviously, for antibiotics, this makes no commercial sense. 

DRIVE AB, an effort funded by the Innovative Medicines Initiative – an effort jointly funded by the European Commission and the European pharmaceutical industry, just published a commentary in Lancet Infectious Diseases (subscription required – why??!! – sorry) where they provide a hint as to what will be appearing in their final report.  The final report is expected sometime around September this year. The commentary, published a week ago, is in the form of an open letter to the G20, whose meeting recently ended. They suggest a market entry award that is fully or partially “de-linked” (from marketing requirements) in the amount of $500 million to $2 billion paid out over 5 years would be a sufficient pull incentive.  The range exists because they would deduct any research and development funding the company had received for the product prior to launch.  There could also be deductions (or rewards) depending on the innovativeness of the new compound or how well it fits into current medical need priorities.  They promise that their full report will provide a rationale for this. I’m not sure that anything less than $1B will work under any circumstances – but that’s just me.

In their open letter, DRIVE AB asks the G20 to establish market entry reward trial programs or pilots to better understand how different models would work on implementation.  I’m at a loss to see how one could set up a “pilot.”  I think you would have to fully fund several different programs to see which one would attract the most or best candidates or which one would best motivate the industry to remain in or restart antibiotic research. But we await Drive AB’s final report here.

The G20’s response on pull incentives (page 8)? - 
Concurrently, in collaboration with relevant experts including from the OECD and the WHO, we will further examine practical market incentive options.

It seems like the G20 will fall back on the “we need more studies” response that was enshrined in the plan recently released by the European Commission (see my last blog). I guess that was predictable.

But here is the problem. Given the persistent market failure as documented by sluggish sales of new antibiotics that are active against resistant pathogens, pharmaceutical companies that are still active in antibiotic research are surely having second thoughts. We may see more departures. Investors, seeing this market failure, are going to become more reticent again after a recent resurgence of interest fueled by optimism regarding both push and pull incentives. 

We need to act now.  Not in ten years.  Lets not wait for another global pandemic such as the one we experienced with MRSA. Please. I ask all of you to write your representatives in government.  In Europe – this means your parliamentarians, your executives, your health authorities, and anyone else you can imagine. In the US – talk to your representatives, your senators, Tom Price at HHS. Let’s get the Infectious Diseases Society even more active than they already are. Let’s start publishing our own open letters that speak to the urgency of this issue.

We need to start drowning our governments with our sense of urgency here before we fall further into the abyss.

Saturday, July 1, 2017

Antibiotics - Europe Leads with a Mixed Message

The European Commission just released a plan for fighting antimicrobial drug resistance. I expected a great deal from Europe given their leadership on the regulatory front and in antimicrobial stewardship efforts.  They have also funded DRIVE-AB that has been studying pull incentives among other approaches to stemming drug resistance. I am guessing that this plan originates partly from DRIVE-ABs efforts.

There is much to like in the plan and I encourage everyone to read it.  Its less than 30 pages and has big print! 

The EU has a great deal to say on infection control and antimicrobial stewardship – all good.

To support the development of novel vaccines, therapeutics and diagnostics, the Commission will,

·      support research into the development of new antimicrobials and alternative products for humans and animals as well as the repurposing of old antimicrobials or the development of new combination therapies;
·      support SMEs (small and medium enterprises) in their R&D efforts towards innovative and/or alternative therapeutic approaches for the treatment or prevention of bacterial infections, together with the EMA;
·      facilitate sharing of antimicrobial research data among relevant stakeholders to guide future antimicrobial medicinal product discovery and development;
·      support the establishment of a European-wide sustainable clinical research network, which should speed up clinical studies on medicinal products, lower their costs, and improve coordination of clinical research;
·      support research and innovation to promote the use of digital technologies supporting the development of new therapeutics and alternatives.

I am most enthusiastic about the funding of R&D for new antimicrobials and the proposed clinical trials network.

In the section on incentives, the Commission proposes to,

analyse EU regulatory tools and incentives – in particular orphan and paediatric legislation– to use them for novel antimicrobials and innovative alternative medicinal products (e.g. vaccines, antibacterial, antifungal, antiviral agents) that currently do not generate sufficientreturns on investment;

Providing key new antimicrobials an orphan drug designation may (or may not) help provide the economic incentive that is needed.  See my previous blog on this.

But, I must admit that I am deeply disappointed with the EU’s treatment of pull incentives.

The Commission will support research into the development of new economic models, exploring and analyzing incentives to boost the development of new therapeutics, alternatives, vaccines and diagnostics.

If we have any more research on models I’m going to explode! DRIVE-AB just finished their research.  The Office of Health Economics has released a number of reports as has the London School of Economics.  This is a way of saying that Europe, as a unified group of nations, is unwilling to commit the resources required to provide the incentives that have already been recommended by others. I suppose it is also possible that the Commission was unable to choose among the various different models for incentives that have already been thoroughly researched and discussed.  This report therefore throws the responsibility for any action on pull incentives back to the various national authorities in Europe.  And it provides those national authorities with an excuse to further delay.  Rome, Nero anyone?

On pull incentives that we so desperately need to fill our lackluster antibacterial pipeline we now have a dearth of leadership.  The US has retreated to Neverland.  Europe is stuck in more bureaucracy. Until there is an outcry by citizens and legislators both in the US and Europe, this is where we will remain.  Are we going to wait for even more widespread more serious drug resistance problem to arise? Will we need an even larger epidemic than those we have already suffered? What will it take to get governments to act?

On the more optimistic side, my spies in Washington tell me that there is an understanding among legislators that something needs to be done. There are apparently two problems that stand in our way.  The first is the political concern around controlling drug prices. How can we propose a pull incentive and claim that it will reduce drug prices? The second is, apparently, that there is disagreement among various stakeholders (read pharmaceutical companies) as to the size of the incentive they think will be required (read – the amount of money they would like). Come on, guys!  Lets get real!

I know that there are a large number of very smart people working on this. But the clock is ticking . . . . Stay tuned.