Sweden to test an access-focused model for new antibiotics: Contracting for Availability

Dear All:

Sweden has been a steady supporter of work on incentives for antibiotics for over a decade – as a reminder, they hosted the 17 Sep 2009 workshop entitled “Innovative Incentives for Effective Antibacterials” that kick-started a conversation between the Swedish and US presidencies that, in turn, generated the momentum that propelled things like the New Drugs For Bad Bugs (ND4BB) project and its subprojects (DRIVE-AB, etc.), TATFAR, and much, much more. 

So, it should be no surprise that Sweden has been working away on how it might constructively engage with the need to reshape the market for new antibiotics. As a consequence of work that started in earnest in 2014, Sweden has initiated a pilot of a partially volume-delinked purchase project for antibiotics that will run through 2022.

And, let me emphasize that this is despite the fact that highly resistant pathogens are really, really rare in Sweden: the entire country of Sweden identified only 94 isolates of carbapenem-resistant Enterobacteriales (CRE) during 2007–13, with only 24 cases of symptomatic CRE infection during this time (Löfmark et al. 2015, link).

 
The details currently in the public domain for the pilot project are spread across several webpages. The easiest place to get started is by reading my translation of the 2-page Swedish FAQ (link). To see everything, follow these steps:

  • The webpage that gets you started is here. This webpage carries
    • A link to an English-language summary report of Sweden’s analyses (link)
    • A link to an FAQ page (link).
  • The FAQ page is in Swedish and provides yet a further link to a 2-page FAQ document in Swedish (link).
    • With a health warning that I do not speak Swedish!: An English-language version of the FAQ (link, same as above) that I created.


Based on details taken from those pages, here’s my summary of the project:

  1. Based on an assignment from the Swedish government and partly financed by Vinnova (Sweden’s innovation agency, link), Sweden wants to establish a Contract for Availability with manufacturers of recently approved drugs that (i) have limited sales and (ii) that cover the three WHO Critical Pathogens (carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae (Enterobacteriales) (for reference, here is a link to my summary of the various lists of priority pathogens).
  2. The heart of the project is that Sweden will offer to pay up to a guaranteed revenue per year to ensure that Sweden can access a certain quantity of each antibiotic within a specified delivery time frame.
  3. The amount to be paid is not yet public but has been estimated from a likely medical worst case need, based on current and projected need over the 2-year contract period.
  4. To compensate for administrative overhead and the requirement to ensure availability within a specified delivery time frame, the guaranteed minimum access payment is scaled up by a factor of 1.5 (150%).
  5. It appears that Sweden would establish a contract for any antibiotic that meets its requirements.
  6. The contracting process is consistent with the Swedish procurement act and will go public at the end of this month via the Swedish Visma TendSign system (link).
  7. The pilot project runs through 2022 and would be reviewed for impact at this point.


The 2-page FAQ document (see links above) provides this really helpful figure. The key concept is that Sweden is promising to pay at a national level the difference between actual regional sales and the guaranteed revenue. If more units are needed (inflection point of the red line shows this), the company’s income goes up:


This is indeed a very interesting variant! Let’s consider it relative to the UK pilot project: Sweden’s intent to contract for all relevant antibiotics is a notable difference from the UK pilot’s intent to run a subscription model for just two drugs (link). Further, the main goal with the Swedish model is not to stimulate R&D but for now simply to guarantee access.

As further context, it is useful to look at the Swedish and UK projects through a DRIVE-AB lens (http://drive-ab.eu/). From that perspective, both projects are versions of the Market Entry Reward (MER) type of Pull incentive recommended by DRIVE-AB. As a reminder, DRIVE-AB recommended two Push incentives (Grants, a Pipeline Coordinator) and two Pull incentives (MER and the Continuity Model). We’ve done well with both of the Push incentives; implementing some form of a MER has been seen as the key next step. If you need more detail on these incentives, see this deck from the final DRIVE-AB meeting or go to this link for even more from that meeting. 


Will this move the needle? Well, we’ll have to think further once more details become available. The idea of contracting for availability is certainly rational from the standpoint of any given country, and especially so for a country that has a low rate of resistance. But, the ability to implement this process relies on the existence of the antibiotic in the first place … if it is does not come to approval or the manufacturer goes out of business, there is nothing for which to contract.

This is, of course, the fire extinguisher problem in a nut shell … at some point, somebody has to pay for them whether they are used or not. You can’t just wish the antibiotic into existence on the afternoon of the day you realize you want it.

And today’s announcement that Tetraphase is being sold to AcelRx for $14.4m (link) is another validation of the urgency for action in this space. Tetraphases’s most recent SEC filing (31 Dec 2019) shows that they had raised just over $600m (link, go to page 74 and look at the line called Accumulated Deficit) … and now they’ve sold for pretty close to the value of cash on hand ($21m on 31 Dec 2019). Basically, everybody who invested has lost money. This is obviously unsustainable!


In summary, it is great to see this experiment go public! Although I would have of course loved to see the project also provide funds at the level needed to stimulate R&D, the mere existence of the pilot is more of a start on this problem than we are seeing from most other countries. The public health leadership of Sweden certainly understands the issue of incentives (they have contributed substantially to the work to date, see introductory comments) and I’m very glad to have them take this first step.
 
Hoping that everyone stays safe in this time of coronavirus (and the Johns Hopkins Covid-19 dashboard, link, is an excellent resource),

All best wishes, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://amr.solutions/blog/. All opinions are my own.

Current funding opportunities:

  • Open now through 16 Mar 2020: CC4CARB, NIAID’s call for applications to fund an innovative Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB). Go here for details.
  • Open now through 9 Apr 2020: NIAID Broad Agency Announcement (BAA) soliciting contract proposals for preclinical and clinical development of vaccines, therapeutic, and diagnostics for microbial pathogens. Go here for more.
  • Dates for the 2020 funding rounds for Novo REPAIR Impact Fund will be announced May 2020. Go here for current details.
  • 2020 funding rounds for CARB-X have not been announced.


Upcoming meetings of interest to the AMR community:

  • 25 Mar 2020 (online): NHS England is holding two webinars on its pilot procurement project. The webinars have the same content, the first is for suppliers (10a-noon UK) and the second is for interested stakeholders (1-3p UK). Go here for a prior newsletter on the project. Details on how to attend the webinars are not yet posted — for now, just mark your calendar.
  • 26 Mar 2020 (online, 17:00-18:30 CET): GARDP REVIVE webinar. Title: “Probability of target attainment analyses for dose selection in antimicrobial drug development,” Speaker: Shampa Das. Go here to register.
  • 30 Mar 2020 (everywhere): Deadline for applications for the Molecular Mycology pathogenesis course at Marine Biological Laboratory, Woods Hole. Now in its 24th year, the hands-on residential course runs 17 July to 2 Aug and gets rave reviews. Go here for more.
  • 9 Apr 2020 (everywhere): Final date for applications for NIAID/DMID call (link) for AMR-related vaccines, therapeutics, and diagnostics.
  • 17 Apr 2020 (online): Pre-ECCMID workshop entitled “Machine Learning for Clinical Microbiology”. Go here for details. 
  • 18-21 Apr 2020 (online): Annual ECCMID meeting (#30)
  • 28 Apr 2020 (online, 17:00-18:30 CEST): GARDP REVIVE webinar. Title: “Inhaled antimicrobials: Do we get the drug to the bug?” Speaker: Harm A. W. M. Tiddens. Go here to register.
  • 5 May 2020 (online, 09:00-10:30 CEST): GARDP REVIVE webinar. Title: “The challenges and opportunities for antimicrobial R&D in low- and middle-income countries – India case study.” Speaker: Anand Anandkumar. Go here to register.
  • 7 May 2020 (Silver Spring): FDA workshop entitled “Development Considerations of Antifungal Drugs to Address Unmet Medical Need.” Go here to register.
  • 8 May 2020 (Silver Spring): FDA workshop entitled “Developing Antifungal Drugs for the Treatment of Coccidiodomycosis (Valley Fever) Infection.” Go here to register.
  • 25-30 May 2020 (Rotterdam), Annual ESPID meeting (European Society for Pediatric ID, #38)
  • 18-22 Jun 2020 (Chicago), ASM Microbe 2020. Go here for details.
  • 27-28 Jun 2020 (Bryant University, Rhode Island): Drug Resistance Gordon Research Seminar entitled “Mechanisms and Approaches to Overcoming Drug Resistance in Cancer, Infectious Disease and Agriculture” for graduate students and postdoctoral scientists. Go here for details … this immediately precedes the GRC listed just next
  • 28 Jun-3 Jul 2020 (Bryant University, Rhode Island): Gordon Research Conference (GRC) entitled “Strategies to Disrupt Drug Resistance in Infectious Disease, Cancer and Agriculture.” Go here for details.
  • 17 Jul-2 Aug 2020 (Marine Biology Laboratory, Woods Hole, MA): Residential course entitled “Molecular Mycology: Current Approaches to Fungal Pathogenesis.” This 2-week intensive training program has run annually for many years and gets outstanding reviews. Go here for details.
  • 2-7 Aug 2020 (Il Ciocco, Tuscany, Italy): Gordon Research Conference (GRC) on Antibacterial Discovery and Development: “Now is the time to re-boot antibiotic R&D before it’s too little, too late.” Go here for details.
  • 24-25 Aug 2020 (Basel): BEAM-, Novo REPAIR-, CARB-X-, DZIF-, ND4BB-, ENABLE-supported (among a long list!) Conference on Novel Antimicrobials and AMR Diagnostics. Details are here.
  • September 2020. University of Sheffield (UK). Applications are being taken for a new 1-year (full-time) or 2-year (part-time) Masters of Science course in Antimicrobial Resistance. The program runs annually from September and covers microbiology, clinical practice and policy. The course webpage is here.
  • 1-4 Sep 2020 (Dublin): Annual ASM-ESCMID Conference on Antibiotic Development #5! Mark your calendar now and go here for details.
  • 9-10 Sep 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
  • 22-25 Sep 2020 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Save-the-date announcement is here, details to follow.
  • [REGISTRATION OPENS SOON] 17-25 Oct 2020 (Annecy, France): Interdisciplinary Course on Antibiotics and Resistance (ICARe). This is a soup-to-nuts residential course on antibiotics, antibiotic resistance, and antibiotic R&D. The course is very intense, very detailed, and gets rave reviews. The date is set for 2020 and the program will ultimately appear here. Registration is limited to 40 students and opens 15 Mar 2020.
  • 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
  • 3-7 Jun 2021 (Anaheim), ASM Microbe 2021. Go here for details.

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