<![CDATA[John H. Rex, MD - Blog]]>Sat, 14 Apr 2018 11:27:21 -0400Weebly<![CDATA[Developing non-traditional antimicrobial therapies & preventatives: Events on 22 April (ECCMID, Madrid) and 14 June (Washington)]]>Wed, 11 Apr 2018 02:55:34 GMThttp://amr.solutions/blog/developing-non-traditional-antimicrobial-therapies-preventatives-events-on-22-april-eccmid-madrid-and-14-june-washingtonDear All:

As recently summarized by Pew Trusts' reviews of the antimicrobial pipeline, there is a lot of interest in non-traditional (alternative) antimicrobial agents but there has also been a lot of concern that they are harder to develop than more traditional agents. If you'll permit me to (briefly) coin the term Fleming Antibiotic to describe things like penicillin, I find it helpful to approach the challenge of non-traditional products by envisioning a continuum defined by these ideas:
  • Fleming antibiotic:
    • Qualitatively, is like a penicillin in that it has the spectrum for a defined syndrome and the speed required to be suitable as standalone therapy (SSSS, if you like acronyms)
    • By virtue of these properties, it is readily developed as monotherapy using standard non-inferiority trial designs.
  • Non-Fleming = non-traditional = everything else
    • This category captures anything not completely having the Spectrum-Syndrome-Speed-Standalone properties of a Fleming Antibiotic. 
    • This can include phage, antibodies, small molecules, large molecules, microbiome ... it doesn't matter. It's non-Fleming because of what it does (or, rather, what it does NOT do).
    • Most often used in combination with a base therapy and hence may have to be studied in a trial where it is possible to see superiority of the combination relative to the base therapy alone. Showing this type of superiority can be very challenging!

I'll admit to having long been fascinated by the potential for non-traditional products: the idea of, for example, a virulence factor inhibitor really appeals to me! But, and as was discussed in Czaplewski et al. "Alternatives to antibiotics—a pipeline portfolio review", LancetID, 2016), such products are often hard to develop because of issues such as the need to show superiority, the very narrow spectrum of some products, and/or product effects that are not well captured by the clinical endpoints used in our trials.

If this tension resonates with your work, you will be interested in knowing about two upcoming discussions of non-traditional products.

First, there is an interactive session on Sunday 22 Apr 2018 during ECCMID (Madrid, 9-11am, Hall G) entitled "Expediting antibacterial development: core lessons and key tools for a rocky road." In a session co-sponsored by CARB-X and GARDP, there will be talks by Marco Caveleri (EMA), Sumati Nambiar (FDA), and William Hope (PK-PD guru). I am the 4th speaker and will be covering the problem of non-traditional products. I am working closely with my co-speakers on this talk with the goal of presenting a good perspective on possible approaches. I'm also going to work with my co-speakers to make the slides from the symposium promptly available.

Second, the Duke-Margolis Health Policy Center has recently announced a 14 June 2018 workshop entitled "Understanding the Development Challenges Associated with Emerging Non-Traditional Antibiotics". Running from 8:30am-5:00pm on that day and supported by a cooperative agreement with FDA, "this public event will focus on the range of non-traditional pharmaceutical approaches being developed to combat bacterial infections. Speakers will address the importance of development in this area, the full spectrum of technologies currently under development, and the outstanding scientific challenges in assessing efficacy of these products in pre-clinical and clinical settings. Discussion will help to prioritize challenge areas in which additional considerations and research will need to be developed moving forward."

I hope to see you at one or both of these events! 

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Novo's REPAIR Fund: Application Template Out (15 May Deadline) + Sr. Associate Job Opening]]>Sun, 01 Apr 2018 17:29:53 GMThttp://amr.solutions/blog/novos-repair-fund-application-template-out-15-may-deadline-sr-associate-job-openingDear All:

The new Novo REPAIR impact fund ($165m over 5 years for antibacterials) is now open for applications -- see the template at this link. Applications are due 15 May.

Relatedly, Novo would like to hire a Senior Associate to help manage the fund. Primary qualifications are (1) scientific understanding of microbiology or a related field (PhD preferred) and (2) at least one year’s investment experience in either venture investing or corporate business development. The position is based in Copenhagen. Inquiries should be made to Hanne Veitland (HVeitland@SpencerStuart.com). 

While you're considering these opportunities, don't forget that...is one of these for you? I hope so! All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Calls for proposals: US CDC, UK-China, Wellcome Trust]]>Fri, 30 Mar 2018 21:16:11 GMThttp://amr.solutions/blog/calls-for-proposals-us-cdc-uk-china-wellcome-trustDear All: As we head into the Easter and Passover weekend, three new calls for proposals have emerged! Perhaps one of these is for you?
  • The US CDC has released a Broad Agency Announcement (FY2018-OADS-BAA) seeking proposals for projects across a range of areas (diagnostics, transmission, microbiome disruption, resistance genes in the environment, and stewardship). Initial proposals are due 16 April 2018.
  • Via Innovate UK, the UK Department of Health and Social Care (DHSC) and The Chinese Ministry of Science and Technology (MOST) have announced a competition in which collaborations between UK- and China-based partners can access £10 million (UK) and 60 million Renminbi (China). The topics of interest include Chinese medicines, new agents, improved used of existing agents, and diagnostics. The competition window is 3 April 2018 to 6 June 2018.
  • The Wellcome Trust is opening a Request for Proposals for an evaluation of the likelihood of successful development and implementation for vaccines against pathogens with high levels of antimicrobial resistance, including a survey of the product development landscape and market analysis. The evaluation will identify barriers to the development and implementation for these vaccines and provide recommendations on the development of these vaccines. See this link for more details. Proposals are due 16 April 2018.

For the first two, see below my signature for a bit more detail. All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

CDC's list of areas: 6 categories spanning 35 AMR-focused topics. Go to this link for the full announcement.
  • New diagnostic, sequencing, and metagenomic tools for AR detection and improved antibiotic use
  • International transmission, colonization, and prevention of AR pathogens
  • Domestic transmission, colonization, and prevention of AR pathogens and C. difficile infections
  • Develop human microbiome disruption indices relevant to AR
  • Resistant pathogens and genes in water systems and the environment and their contribution to human infections
  • Improving antibiotic stewardship

Innovate UK - DHSC - MOST areas of interest: Go to this link for the full announcement
  • explore opportunities from traditional Chinese medicine for the treatment or prevention of infectious bacterial diseases in humans or animals
  • advance the discovery of new agents to prevent or treat drug-resistant bacterial infection in humans or livestock. New agents could include small molecule drugs, vaccines, antibodies or other biological products
  • identify new agents that will increase the feed energy conversion in livestock. This should be done without use of antibiotics or hormones
  • use modelling and prospective and retrospective clinical studies to maximise the clinical utility of current antibiotics. Focus especially on those against drug-resistant Gram-negative bacteria. Projects must aim to improve the prognosis of patients with extensively drug-resistant infections
  • improve capabilities for the diagnosis, treatment selection and surveillance of bacterial infections and antibacterial resistance

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Leadership opportunities in AMR: PACCCARB, BARDA's new DRIVe initiative]]>Sat, 24 Mar 2018 04:00:00 GMThttp://amr.solutions/blog/leadership-opportunities-in-amr-pacccarb-bardas-new-drivee-initiativeDear All: If you are interested in public service, two very exciting groups of opportunities have recently emerged.

First, PACCARB (the US Presidential Advisory Council for the CARB initiative) is about to have its first rotation of voting members. Of the original fifteen voting members appointed just under 3 years ago, seven us (myself included) are due to rotate off later this year (the others will rotate off next year after serving for 4 years). Nominations to fill these seven voting positions are now being sought. Newly appointed voting members would serve either a three- or four-year term. If you are interested, check out the solicitation page here. Nominations must be received by 5:00p (Washington DC time) on 30 Apr 2018. I've very much enjoyed my time on PACCARB and would commend it to others who are interested in this type of service.

Second, BARDA is launching an exciting new research group. Called the Division for Research, Innovation and Ventures (DRIVe), the new group seeks to develop countermeasures to protect Americans from natural and intentional health security threats. Up to 20 new federal and contractor staff are being sought in the next 60 days to support the launch of this new initiative! Many more details, including contact information and a list of possible roles, can be found below my signature.

The amount of AMR-related activity is amazing! All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html


BARDA's DRIVe initiative (text adapted from an announcement email)
The Biomedical Advanced Research and Development Authority (BARDA) serves the nation by partnering with industry to make available medical countermeasures against wide range of major threats to our health security.  A component of the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services, BARDA has been successful in delivering new therapeutics, vaccines, diagnostics and devices against serious health threats including biological, chemical, radiological, nuclear agents, emerging infectious diseases and their sequelae. 
 
As a priority for the Assistant Secretary for Preparedness and Response, BARDA will be launching in June 2018 a new Division for Research, Innovation and Ventures (DRIVe) to accelerate the research, development, and availability of transformative countermeasures to protect Americans from natural and intentional health security threats. DRIVe will initially accelerate the development of innovative solutions in its first two target impact areas of sepsis and pre-exposure, pre-symptomatic diagnostics. DRIVe will expand in future years to tackle additional challenges.
 
DRIVe will also lead BARDA’s Medical Countermeasure Innovation Partnership (MCIP) established under 21st Century Cures. DRIVe will accelerate the development of innovative medical countermeasures not only through direct research and development, the traditional BARDA model, but also through the use of an independent 3rd party partner that leverages strategic venture capital practices and methods, akin to a corporate venture capital model. Together both of these models will stimulate innovation. 
 
BARDA might be looking for you! DRIVe is actively looking to recruit up to 20 new federal and contractor staff in the next 60 days in preparation for its launch during June 2018. Per BARDA, "If you are interested in being part of DRIVe, to accelerate new medical countermeasures to protect America and the world against the relentless national security threats posed by terrorists, rogue nation states and naturally emerging diseases we have a place for you on our team! We want to target the innovators, the thought leaders and those who have a vision for how medicine will be practiced in the future.  Someone who won’t take no for an answer or hide behind the belief that ‘this is too hard’."

Below are lists of the initial current positions now being recruited to support DRIVe. For more details, please contact:

    Tyler G. Merkeley 
    Health Scientist 
    Biomedical Advanced Research and Development Authority (BARDA) 
    Office of Assistant Secretary for Preparedness and Response (ASPR)
    U.S. Department of Health and Human Services (HHS)
    Email: DRIVe@HHS.gov
 

Sepsis Product Development SME (Subject Matter Expert)
Job City: Washington 
Job State: US - DC 
http://chk.tbe.taleo.net/chk05/ats/careers/requisition.jsp?org=TUNNELL&cws=4&rid=8930
 
Senior Financial and Business Development SME (Subject Matter Expert) [VC Experience 15-20 years]
Job City: Washington 
Job State: US - DC 
http://chk.tbe.taleo.net/chk05/ats/careers/requisition.jsp?org=TUNNELL&cws=4&rid=8932
 
Medical and Novel Healthcare Diagnostics SME (Subject Matter Expert)
Job City: Washington 
Job State: US - DC 
http://chk.tbe.taleo.net/chk05/ats/careers/requisition.jsp?org=TUNNELL&cws=4&rid=8931
 
Senior Research Scientist SME (Subject Matter Expert)
Job City: Washington 
Job State: US - DC 
http://chk.tbe.taleo.net/chk05/ats/careers/requisition.jsp?org=TUNNELL&cws=4&rid=8934

Sr. Analytical Consultant [Scientist Technology Support - 2 Positions] 
US-DC-Washington  
https://careers-aveshka.icims.com/jobs/1188/sr.-analytical-consultant/job
 
Business Consultant [Venture Capital Experience 6-8 years]
https://careers-aveshka.icims.com/jobs/intro
Job Locations US-DC-Washington
Link not yet available 
 
Executive Assistant for DRIVe
Job LocationsUS-DC-Washington
https://careers-aveshka.icims.com/jobs/1183/executive-assistant/job
 
Sr. Business Consultant with DARPA Experience
US-DC-Washington
https://careers-aveshka.icims.com/jobs/1185/sr.-business-consultant/job
 

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[EU Joint Action on AMR & Health-Care Associated Infections (EU-JAMRAI): Passing the DRIVE-AB torch?]]>Tue, 20 Mar 2018 13:31:07 GMThttp://amr.solutions/blog/eu-joint-action-on-amr-health-care-associated-infections-eu-jamrai-passing-the-drive-ab-torchDear All:

Recently announced is a new EU Joint Action on Antimicrobial Resistance (AMR) & Health-Care Associated Infections (HCAI). Its acronym is EU-JAMRAI and the website is https://eu-jamrai.eu/.

Joint actions are a common tool for coordinating implementation activities across Europe. EU-JAMRAI actually started in September 2017 and will run for three years but it is really launching itself now into the public eye with a website and newsletter. EU-JAMRAI has nine work packages (WPs, the full list is found below my signature).

Why does this matter? The bulk of EU-JAMRAI's activity will focus on ensuring that solid national action plans exist in EU member states. But of great interest to the R&D community, it appears that WP9 (led by France and Norway) will be looking at pull incentives for Europe. To my eye, this is a very exciting development: With DRIVE-AB having come to an end with release of its final report, there is definitely a need for the torch to pass to a new group that can carry this work forward.

So, check out their website and subscribe to their newsletter! The link to subscribe to the newsletter is in the middle of the JAMRAI homepage (look just above the picture of the pigs) and unfortunately is structured so that I can't put a copy of the signup link here.

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

The Work Packages of EU-JAMRAI
  • Four WPs focus on project coordination, dissemination/communication of results, and evaluation of progress (WPs 1, 2, 3, and 8).
  • Two of the WPs (4 & 5) focus on implementation of One Health national strategies and national action plans.
  • WP6 seeks to create and implement policies to prevent HCAI
  • WP7 will create a database of current guidelines for antibiotic stewardship in animals & man
  • WP9 work seeks to ensure that national processes for R&D are coordinated with the One Health Approach. This WP will also explore mechanisms to increase innovation, including exploration of Pull incentives.

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Wellcome Trust: RFP to develop a business plan for a sustainable clinical trial network]]>Tue, 06 Mar 2018 02:23:52 GMThttp://amr.solutions/blog/wellcome-trust-rfp-to-develop-a-business-plan-for-a-sustainable-clinical-trial-network​Dear All:

Just released today is an RFP (see text just below my signature) to develop a business plan for the design, funding, and implementation of a sustainable clinical trial network for developing new antibacterial agents. 

The core of this idea emerged in early 2016 based on debates about the potential value of a network focused on a specific infection (e.g., nosocomial pneumonia) in which a standing protocol randomized subjects to a well-accepted standard comparator (probably a carbapenem) or a rotating series of investigational agents. A group of us summarized the key elements of the idea in this 2016 paper in Clinical Infectious Diseases. Here's a visual illustration of the concept:
Figure legend from the CID paper: Shown are 3 years in the life of a network. To start the network, a target infection is chosen, a standard protocol is prepared, and a widely registered excellent standard comparator (control A) is selected. After a brief run-in period, test drugs are flexibly added and removed from the network. A constant control arm (control A) is envisioned, but alternative controls can also be used as needed to address issues such as blinding (control B paired with test 2). Multiple agents can be in the network simultaneously. It is also assumed that data on control agents can be shared across drugs.

The goal of the network is to reliably provide sponsors with a data from a properly powered and designed non-inferiority study that would serve as the basis for registration. When combined with implementation by the sponsor of a separate MDR/XDR study, you have the essence of a Tier B trial program.

The network study would be implemented in UDR (Usual Drug Resistance) settings in which a standard comparator such as a carbapenem would be acceptable. Sharing of controls and elimination of study startup delays for each new drug are estimated to reduce cost and time by ~40% for drugs using the network. Continuity for sites and investigators is provided by the ongoing nature of the network.

First discussed in early 2016, it is exciting to see Wellcome taking the next step towards making this concept a reality! Contact details are provided below should you or a colleague be interested in taking up this challenge. Expressions of interest are due by 12 March.

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Wellcome Trust RFP (Request for proposals)
We’re looking to commission an organisation or consortium with understanding of the development and operations of clinical trial networks.
 
This follows our report on the importance of clinical trial networks for antibiotic development, and how they should be developed.
 
The purpose of this commission is to develop a business plan for the design, funding and implementation of a sustainable clinical trial network for infectious diseases centred specifically on antibiotic development.
 
The network should be able to:
  • generate comparative data on new agents quickly and efficiently
  • evaluate more than one investigational agent at a time using a standardised master protocol for each infection.
 
Our aim is that the findings from this work will inform the development of a new clinical trials network, helping to reduce costs, get clinical trials up and running more quickly, and lead to shorter late-stage trials.
 
Supporting documents, including a detailed timeline can be found on our website.
 
For more information or to express your interest, please email CTNetwork@wellcome.ac.uk. The deadline for expressing interest is Monday 12 March, 23:59 GMT.

 

Upcoming meetings of interest to the AMR community:
]]>
<![CDATA[Novo's $165m REPAIR fund seeks to support projects from LO to Phase 1]]>Wed, 28 Feb 2018 05:00:00 GMThttp://amr.solutions/blog/novos-165m-repair-fund-seeks-to-support-projects-from-lo-to-phase-1Dear All:

Just announced today (press release, website), Novo Holdings has created a $165m impact fund that seeks to support novel therapies from Lead Optimization (LO) through Phase 1. The fund specifically targets "first-in-class therapies, covering small molecules, biologics, and new modalities." Similar to the focus of CARB-X, REPAIR (Replenishing and Enabling the Pipeline for Anti-Infective Resistance) will focus on priority pathogens from the CDC and WHO priority lists. 

The origin of the idea for this project appears to be from social impact goals of the Novo Nordisk Foundation: "The vision of the Foundation is to contribute significantly to research and development that improves the health and welfare of people. The Foundation donates about $300-600 million per year primarily for medical research."

A first round of investments dedicated to European companies will start in April 2018 (non-confidential presentations can be sent until 15 May 2018) and is expected to lead to investments by the end of 2018. A second round of investments focusing on United States companies will start in the fall 2018.

All told, the fund expects to invest USD 20-40 million per year over 3–5 years in about 20 projects in Europe and the United States. The overall goal is at least one new therapy reaching the market.

It's exciting to see this additional source of push funding! Although funds from REPAIR are presumably dilutive in nature (rather than the non-dilutive financing of CARB-X), the availability of funds from a group who understand the challenge and opportunity of antimicrobial resistance will be a powerful new force for progress. Thank you, Team Novo!

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[(Another!) FDA trial design workshop: Complex innovative designs]]>Sun, 25 Feb 2018 00:38:53 GMThttp://amr.solutions/blog/another-fda-trial-design-workshop-complex-innovative-designsDear All:

Adding to the 19 Mar 2018 (Designs for Rare Diseases) and 16 Apr 2018 (Inclusion/Exclusion criteria) workshops already announced (see list below), FDA has now announced a 20 Mar 2018 workshop on complex innovative designs (CID) in clinical drug trials. From the Federal Register notice, we are told that the workshop seeks to (1) facilitate discussion and information sharing about the use of CID in drug development and regulatory decision making and (2) obtain input from stakeholders about a CID pilot program. Ideas to be discussed include complex adaptive designs, use of external/historical control subjects, Bayesian designs, master protocols, clinical trial simulations, and the proposed CID pilot program.

Why is this relevant to those of us working on new approaches to antimicrobial resistance (AMR)? Although AMR does not appear in the titles of any of these workshops, some of the ideas could be (or could become) very relevant for the AMR community.

In particular, the mathematics of rare events make it hard to develop narrow-spectrum agents outside of a few special situations. As non-traditional alternative therapies are often narrow-spectrum (e.g., most monoclonal antibody approaches), we simply must find ways forward lest we never develop such products. 

We've had several public discussions on this problem (see this note for further details) and we're definitely not done with the conversation. As the ideas to be discussed in the upcoming workshops might help us with trial designs for narrow-spectrum products, I'm delighted to see them on the calendar! Also, the mention of a pilot program for complex innovative designs is new and of interest. 

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[TATFAR's 2018 meeting: Live streaming of 7 Mar opening session]]>Thu, 22 Feb 2018 20:48:59 GMThttp://amr.solutions/blog/tatfars-2018-meeting-live-streaming-of-7-mar-opening-sessionDear All: On 7-9 Mar 2018, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) will meet in Atlanta, GA to discuss:
  • Improving antibiotic use in humans and animals,
  • Preventing infections and their spread, and
  • Strengthening the drug pipeline.
The opening session (8.30-10.00a EST on 7 Mar) will be available for viewing via live-streaming

What is TATFAR? Created in 2009, TATFAR comprises AMR-focused government-level experts from Canada, the European Union (EU), Norway, and the United States. CDC maintains the secretariat for the group. TATFAR is currently working on implementation of a set of policy recommendations that span antibiotic use (human & veterinary), infection prevention, and strategies for improving the pipeline of new therapeutic options.

There's no public agenda for the full meeting, but I infer that the focus is on reviewing progress to date and the need for any updates to TATFAR's current policy recommendations. It's great to see our government partners maintaining steady effort on the important problem of antimicrobial-resistant infections!

Why does a meeting of TATFAR matter? As a lot of the needed change requires government-level action, having a knowledgeable and engaged government-based effort is critical for any progress. No, we don't yet have the drugs we need -- but we do have a lot of push incentives, a growing pipeline of both traditional and non-traditional products, and a supportive regulatory environment. No, we don't yet have pull incentives -- but the recent DRIVE-AB reports plus the prior work of the UK AMR Review and the Duke-Margolis project on incentives are driving substantive conversations on both sides of the Atlantic.

In short, the very existence of this group is one of many positive signs in this space. I hope you can make time to dial-in to get a feel for what our government-based colleagues are doing. My own view is that the overall trajectory gives hope that we may yet have the tools needed for ourselves, our children, and our grandchildren.

Many thanks to all who engaged with making this happen! All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[CARB-X Application Round #3 goes live!]]>Tue, 20 Feb 2018 16:35:04 GMThttp://amr.solutions/blog/carb-x-application-round-3-goes-liveDear All:

The wait is over -- CARB-X has today released a call for new applications! The call has an interesting 2-round structure and you'll need to study carefully both the press release and the supplemental details document to understand where your program would fit. Here's my summary:
  • Round 1:
    • Submission window for Expressions of Interest: 22-29 March 2018
    • Scope: Restricted to new classes of direct-acting small molecule and large molecule antibacterials that have potential to cover the top 6 Gram-negative pathogen groups from the WHO and CDC priority listsA. baumannii (carbapenem-R), P. aeruginosa (carbapenem-R), Enterobacteriaceae (carbapenem-R and/or 3rd-gen ceph-R), Salmonellae spp. (fluoroquinolone-R), N. gonorrhoeae (3rd-gen ceph-R, fluoroquinolone-R), and Shigella spp. (fluoroquinolone-R).
  • Round 2:
    • Submission window for Expressions of Interest: 1-8 June 2018
    • Scope: Both direct- and indirect-acting therapeutics as well as vaccines, diagnostics and devices that meet certain criteria.
    • In terms of therapeutics, both novel and known classes are acceptable.
The very tight focus of Round #1 feels right to me ... we really need to push hard at a global level on the creation of entirely novel classes of direct-acting agents. These will be rare but they are needed.

The scope of Round #2 is then broad and roughly comparable to the scope of prior CARB-X funding rounds.

With an announced portfolio of more than 20 projects and its search for both new accelerators and new staff, CARB-X continues to lead the charge against AMR. Exciting times! 

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Duke-Margolis & FDA: Workshop on stats & methods for rare diseases]]>Wed, 14 Feb 2018 18:43:21 GMThttp://amr.solutions/blog/duke-margolis-fda-workshop-on-stats-methods-for-rare-diseasesDear All:

Duke-Margolis and FDA have now announced a 19 Mar 2018 workshop entitled Utilizing Innovative Statistical Methods and Trial Designs in Rare Disease Drug Development (FR notice). Here's the teaser from the web: "Convened by the Duke-Robert J. Margolis, MD, Center for Health Policy at Duke University and supported by a cooperative agreement with FDA, this public event will bring the stakeholder community together to discuss the challenges that rare disease settings pose for treatment development and regulatory decision-making, as well as the promising study designs and analytical methods that can help overcome them. The day’s discussion will center around novel approaches to trial design and analysis to improve efficiency and interpretability of results in rare disease trials."

Note how neatly this fits with their previously announced 16 April 2018 1-day workshop on inclusion and exclusion criteria in clinical trials (corresponding FR notice): "The purpose of the public meeting is to bring the stakeholder community together to discuss a variety of topics related to eligibility criteria in clinical trials and their potential impact on patient access to investigational drugs, and how to facilitate the enrollment of a diverse patient population." 

This is great to see! While neither of these two is specifically focused on AMR-related issues, the applicability to our trial design issues should be obvious. Unfortunately, I am probably going to miss both workshops but I hope that at least a few of you will get there, especially for the 19 Mar workshop on statistical design. If you do go, I'd love to share what you learned with the newsletter community ... please let me know!

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[More jobs! CARB-X also has openings]]>Wed, 07 Feb 2018 18:35:17 GMThttp://amr.solutions/blog/more-jobs-carb-x-also-has-openingsDear All:

Building on my recent note about a search for the G20 secretariat lead, we now have CARB-X getting into job creation mode by posting 8 positions across 5 different job openings:
  • Accelerator Lead: coordinates the work of the growing accelerator network for all CARB-X-funded companies.
  • Support Team Lead (three positions): takes responsibility for managing the full range of support capabilities for 10-15 biotech and pharma companies in the Powered by CARB-X portfolio.
  • Director of Finance and Compliance: coordinates multiple partners and sub-grant recipients to ensure financial operations are in line with plans, plays a critical role in budget forecasting and planning processes, and more.
  • Project Manager: plays a critical role in the planning and execution of the funding cycles and coordination of pre-award and post-award activities.
  • Cycle Lead (two positions): takes full ownership of $20-50M funding Cycles from the preparatory stages through the three step application process, leading to the selection of a dozen or more additional companies for milestone-based awards.
As you hopefully already know, CARB-X began mid-2016 to award more than $455 million for research over a five-year period. I recently wrote about their search for new accelerators and it is good to see this continued expansion of their team. As one of the largest public-private research partnerships in the world. CARB-X is building an extraordinary pipeline of AMR-focused projects. If one of these opportunities intrigues, please check out the complete job postings online.

All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Two things: WHO's looking GLASS + FDA's advances with PDUFA VI]]>Tue, 06 Feb 2018 05:00:00 GMThttp://amr.solutions/blog/two-things-whos-looking-glass-fdas-advances-with-pdufa-viDear All: Two things today. Unrelated, but both relevant!

WHO's GLASS: WHO's Global Antimicrobial Resistance Surveillance System (GLASS) was created during October 2015 and seeks to obtain coordinated and consistent global estimates on resistance rates. In a major report released on 29 Jan 2018, GLASS now provides provides official national AMR data for the period 2016-17 from 40 countries based on testing of 507,746 isolates of Acinetobacter spp., Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, Salmonella spp., Shigella spp., Staphylococcus aureus, and Streptococcus pneumoniae. Participating countries span the globe:

​The good news
 is that GLASS exists and that countries are making progress on creating National Coordination Centres (NCCs), National Reference Laboratories (NRLs), and sentinel surveillance sites. Progress is (no surprise) somewhat uneven, but the real point is that progress is happening.

The bad news is that substantial rates of resistance are seen world-wide. There is no single best way to summarize this, but here is an example of a resistance rate summary that you can find in the report (x-axis is % non-susceptible). Note the nearly 25% rate of imipenem resistance!
Scary!

FDA & PDUFA VI: FDA posted a small business-focused analysis of PDUFA VI back in November 2017 that I only recently learned about. As a reminder, the Prescription Drug User Fee Act (PDUFA) has been an evolving legislative series by which FDA collects fees that it then uses to make the drug review process more efficient while not compromising drug safety. There are many changes in PDUFA VI (please see the full summary here), but these are notable to my eye:
  • Early Consultation on the Use of New Surrogate Endpoints: Early consultation between the FDA and sponsors can now occur when the sponsor intends to use a biomarker as a new surrogate endpoint that has never been previously used as the primary basis for product approval in the proposed context of use.
  • Advancing Development of Drugs for Rare Diseases:  CDER’s Rare Disease Program staff will provide their expertise on approaches to studying and reviewing such drugs, continue to foster collaborations in the development of tools and data to support rare disease drug development, and facilitate interactions to increase awareness of FDA programs and engagement of patients in the decision-making process.
  • Advancing the Use of Complex Innovative Trial Designs and Model Informed Drug Development: FDA will conduct activities to facilitate the development and application of exposure-based, biological, and statistical models derived from preclinical and clinical data sources.
I hope you'll quickly see why these are relevant to antimicobial agents: we've mused on surrogate endpoints (but time courses for major infections are so quick that it's generally better to just get a real endpoint), we've discussed at length the problem of rare species (see materials from the 13 April 2017 AMDAC plus my blog on same), and we debated the question of alternative trial designs during the 18-19 July 2016 workshop discussion of hypothetical Drug X-1.

And, this sheds some light on the recently announced Duke-Margolis 1-day workshop on inclusion and exclusion criteria in clinical trials on 16 April 2018 as part of a cooperative agreement with FDA (corresponding FR notice) which will "discuss a variety of topics related to eligibility criteria in clinical trials and their potential impact on patient access to investigational drugs, and how to facilitate the enrollment of a diverse patient population."

It all makes your head spin! Although we don't know the pace with which all this will happen, it certainly reminds me of Picabia's comment that "Our heads are round so our thoughts can change direction." 

Buckle up! --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:
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<![CDATA[Secretariat Lead of the G20's Global AMR R&D Hub: Could this be you?]]>Mon, 05 Feb 2018 01:34:07 GMThttp://amr.solutions/blog/secretariat-lead-of-the-g20s-global-amr-rd-hub-could-this-be-youDear All:

As you may know, the G20 are establishing an AMR R&D Hub that will encourage and promote coordinated global action on AMR. The hub will be based in the Berlin office of the German Center for Infection Research (DZIF) and Germany will finance it for the first three years. There is now a public call to recruit the leader of this hub. Here is the key text from the the online job description (emphasis is mine):

In their Declaration from July 7 and 8, 2017 the G20 Leaders “call for a new international R&D Collaboration Hub to maximize the impact of existing and new antimicrobial basic and clinical research initiatives as well as product development”. This Global AMR R&D Hub shall promote high-level coordination and alignment of the existing public and private funding and leverage further investments for AMR R&D initiatives on a national and/or international level. The Global AMR R&D Hub shall become a central platform to provide guidance for governments and non-governmental funders on R&D funding priorities in the field. The scope of the Global AMR R&D Hub is embedded in a comprehensive One Health Approach, comprising human and animal health as well as environmental aspects. Initially, the activities of the Global AMR R&D Hub shall focus on enabling the development of urgently needed products for the prevention, treatment and diagnosis of bacterial infections in humans.

For the implementation of the Global AMR R&D Hub a secretariat with up to five employees (including the position announced below) will be established within the German Center for Infection Research (DZIF) in Berlin, Germany. We are currently searching for one Secretariat Lead (Senior Level).


Could this be you or somebody you know? Please be sure to share this interesting and important job opportunity! All best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>
<![CDATA[Potpourri: QIDP Q&A, BEAM Alliance paper and meeting, Duke-Margolis workshop on inclusion/exclusion criteria]]>Mon, 29 Jan 2018 22:35:41 GMThttp://amr.solutions/blog/potpourri-qidp-qa-beam-alliance-paper-and-meeting-duke-margolis-workshop-on-inclusionexclusion-criteriaDear All: And then there are days when the floodgates open and things just appear! The amount of stuff afoot is amazing...

QIDP Q&A: FDA has released a draft Q&A guidance document on QIDP. Dated January 2018 (and posted as of 30 Jan 2018 via this FR notice, this guidance covers such topics as required information, whether QIDP is limited to just things that treat or whether things that treat, diagnose, or prevent qualify (yes, all are OK), and more. 

The BEAM Alliance has been busy! First (and somehow I missed this), BEAM (Biotech companies in Europe combating AntiMicrobial Resistance) released a well-written multi-company authored position paper back in Nov 2017 on the need for AMR-related incentives to consider the needs of SMEs. This paper sits nicely alongside the materials I reviewed in my recent "Push! Pull! Push! Pull! Davos Highlights" newsletter. To further support their efforts to build the European biotech ecosystem, BEAM is organizing a 1-day AMR-focused meeting in Berlin on 2 Mar 2018. Good work, Team BEAM!

Duke-Margolis is hosting a 1-day workshop on inclusion and exclusion criteria in clinical trials on 16 April 2018 as part of a cooperative agreement with FDA (corresponding FR notice): "The purpose of the public meeting is to bring the stakeholder community together to discuss a variety of topics related to eligibility criteria in clinical trials and their potential impact on patient access to investigational drugs, and how to facilitate the enrollment of a diverse patient population." This looks to me to be very general in nature -- there is nothing in the material online that speaks specifically to AMR. Nonetheless, I am sharing it given some of the debates we've had about inclusion & exclusion (especially, for example, prior antibiotics). If you any of you happen to attend, please drop me a note should there be material of relevance for the community.

And that's all for today! Best wishes, --jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: http://amr.solutions/blog-index.html

Upcoming meetings of interest to the AMR community:]]>