AMR.Solutions

Updated FDA Q&A on Antibacterials for Unmet Medical Need

Dear All,

An updated version of FDA’s very helpful Q&A entitled “Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases – Questions and Answers” has just been released. Here are the links you need to get started:

  1. The new June 2025 guidance itself
  2. [key context] The 27 May 2022 newsletter that discussed both the prior FDA iterations of this guidance (May 2022, August 2017) as well as a pair of EMA guidance documents (a general guidance, a pediatric guidance) that were also released May 2022
  3. This 2024 paper by FDA staff: Ghosh M, Iarikov D, Qi X, Rubin D, Shurland S, Goodwin A, Wei X, Chilukuri D, McMaster O, Miller T, Kim P, & Sherwat A. Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs. Emerging Infectious Disease journal. 2024;30(11):2227; https://doi.org/10.3201/eid3011.231416.
    • This paper is notable for its detailed discussion of the path to approval for  sulbactam-durlobactam (XACDURO) for HABP-VABP for Acinetobacter baumannii via a non-inferiority trial that used a 20% non-inferiority margin. For an even deeper dive, the materials from the 17 April 2023 FDA AMDAC (Antimicrobial Drugs Advisory Committee) meeting are available online.
  4. And if you need a refresh on non-inferiority trials, see the 19 Sep 2020 newsletter entitled “In Praise of Non-Inferiority” and its associated YouTube video explainer.

To get your head in the game for this update, a bit of background refresh is helpful. First, re-read the background in the 27 May 2022 newsletter. Then, read the 2024 paper from FDA. Finally, brush up on non-inferiority with the 19 Sep 2020 newsletter.

With those steps taken, you are now ready for the 2025 update! To set the scene, we have this background from the Federal Register notice:

  • This guidance finalizes the draft guidance entitled “Antibacterial Therapies for Patients With an Unmet Medical Need for the Treatment of Serious Bacterial Diseases—Questions and Answers (Revision 1)” issued on May 24, 2022 (87 FR 31568).
  • FDA provided clarifying edits to the final guidance and included additional information after considering comments received on the draft guidance. 
  • Edits included deleting the nested noninferiority trials/superiority clinical trials section “because of difficulty in interpreting such trials”, updating the add-on superiority trial design section, and updating the discussion of studies that combine data from subjects with infections at different body sites. The difficulty with interpretation of nested trials is not further discussed, but there is a hint in the guidance itself that this relates in part to the problem of combining data across body sites (see also below).

Going into a bit more detail, my summary of changes is as follows:

  1. (Overall) There are no dramatic changes … the updates are a combination of clarification and simplification.
  2. These points have been added for emphasis:
    1. Advantage can be efficacy or safety: “Antibacterial drugs that offer an efficacy advantage over available treatments for serious bacterial infections may be eligible, as may antibacterial drugs that offer a safety advantage over existing treatments for serious bacterial infections…”
    2. The fundamental basis of approval is unchanged (and in particular, efficacy must still be demonstrated): Text in Q&A #11 on this point is unchanged but the much earlier Q&A #3 now emphasizes that “A sponsor … must still provide adequate data to demonstrate that the drug is safe and effective to meet the statutory standards for approval.”
  3. Statistical flexibility is possible:
    1. There is new text in the discussion of superiority design trials that builds on hint from the 2022 document about using a “less stringent type I error rate”: “A typical criterion for concluding that a superiority trial is positive (showed an effect) is a p value of <0.05 (two sided). A lower p value, for example, would often be expected for reliance on a single trial. For a serious bacterial disease with no available therapy or a rare disease where sample size might be limited, a somewhat higher p value—if prespecified and appropriately justified—might be acceptable.”
    2. As a further example, note the relatively large (20%) non-inferiority margin discussed in Ghosh 2024 (for reference, you can review Rex et al. 2017 for a discussion of typical margin sizes). In some settings, you can make an argument for this sort of stretch. 
  4. The potential role of add-on superiority is highlighted: “Substantial evidence of effectiveness of an investigational drug may also be demonstrated in an add-on placebo-controlled superiority trial design in which all subjects also receive standard or best available treatment.”
  5. The discussion of nested non-inferiority/superior designs is now gone and the discussion of combining data on infections at multiple body sites is very much simplified. The comment in the FR (above) makes it clear that using nested non-inferiority/superior has proven challenging. The comments on combining body sites also suggest complexity (for example, a prior comment about Bayesian modeling is now gone) and conversation with FDA is encouraged if you want to pursue this path.
  6. (minor) Text regarding use of the so-called animal rule has been deleted.
    1. The May 2022 version included Q&A #13 which said “When human clinical effectiveness trials can be conducted, drugs are not eligible for approval under the so-called animal rule…”
    2. I don’t know why this was deleted as I would expect it to still be true. 

All in all, a very helpful update! With thanks to our colleagues at FDA and with 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

  • The AMR Industry Alliance is again offering a Stewardship Prize of 10,000 CHF to recognize innovative approaches to combating AMR in low-to-moderate-income countries. This year’s prize focuses on utilizing diagnostics in stewardship efforts. Applications are due by 1 Sep 2025. Go here for details and to apply.
  • NNF (Novo Nordisk Foundation) have announced their “Challenge Programme 2026 – Unravelling the Pathways of Human Invasive Fungal Diseases. The call seeks applications from EU-centered consortia (global partners are possible) for research in 4 areas: (i) fungal virulence factors, (ii) host-pathogen interactions, (iii) mechanisms of anti-fungal resistance, and (iv) fungal disease markers. Applications are due by 8 Oct 2025. Go here for details. 
  • ENABLE-2 has continuously open calls for both its Hit-to-Lead program as well as its Hit Identification/Validation incubator. Applicants must be academics and non-profits in Europe due to restrictions from the funders. Applications are evaluated in cycles … see the website for details on current timing for reviews. 
  • CARB-X will have two calls during 2025 that span two areas: (i) Small molecules for Gram-negatives (the focus is on Pseudomonas aeruginosa) and (ii) Diagnostics for typhoid (the focus is diagnosis of acute infections in 60 minutes or less). See this 26 Feb 2025 newsletter for a discussion of the call and go here for the CARB-X webpage on the call. The first cycle is now closed (it ran16-30 April 2025); the 2nd round will be open 1-12 Dec 2025.
  • BARDA’s long-running BAA (Broad Agency Announcement) for medical countermeasures (MCMs) for chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza, and emerging infectious diseases is now BAA-23-100-SOL-00004 and offers support for both antibacterial and antifungal agents (as well as antivirals, antitoxins, diagnostics, and more). Note especially these Areas of Interest: Area 3.1 (MDR Bacteria and Biothreat Pathogens), Area 3.2 (MDR Fungal Infections), and Area 7.2 (Antibiotic Resistance Diagnostics for Priority Bacterial Pathogens). Although prior BAAs used a rolling cycle of 4 deadlines/year, the updated BAA released 26 Sep 2023 has a 5-year application period that ends 25 Sep 2028 and is open to applicants regardless of location: BARDA seeks the best science from anywhere in the world! See also this newsletter for further comments on the BAA and its areas of interest.
  • HERA Invest was launched August 2023 with €100 million to support innovative EU-based SMEs in the early and late phases of clinical trials. Part of the InvestEU program supporting sustainable investment, innovation, and job creation in Europe, HERA Invest is open for application to companies developing medical countermeasures that address one of the following cross-border health threats: (i) Pathogens with pandemic or epidemic potential, (ii) Chemical, biological, radiological and nuclear (CBRN) threats originating from accidental or deliberate release, and (iii) Antimicrobial resistance (AMR). Non-dilutive venture loans covering up to 50% of investment costs are available. A closing date is not posted insofar as I can see — applications are accepted on a rolling basis; go here for more details.
  • The AMR Action Fund is open on an ongoing basis to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
  • These things aren’t sources of funds but would help you develop funding applications
    • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
    • Antimicrobial Resistance Research and Innovation in Australia is an actively updated summary that covers Australia’s AMR research and patent landscape. It is provided via collaboration between The Lens (an ambitious project seeking to discover, analyse, and map global innovation knowledge) and CSIRO (Commonwealth Scientific and Industrial Research Organisation, an Australian Government agency responsible for scientific research). Lots to explore here!
    • Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-X, C-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).

John’s Top Recurring Meetings
Virtual meetings are easy to attend, but regular attendance at annual in-person events is the key to building your network and gaining deeper insight. My personal favorites for such in-person meetings are below. Of particular value for developers, the small meeting format of BEAM’s AMR Conference (March) and GAMRIC (September-October; formerly, the ESCMID-ASM conference series) creates excellent global networking. IDWeek (October) and ECCMID (April) are much larger meetings but also provide opportunities for networking with a substantial, focused audience via their Pipeline sessions. Hope to see you there!

  • 1-3 Oct 2025 GAMRIC, the Global AMR Innovators Conference (London, UK). Formerly the ESCMID-ASM Joint Conference on Drug Development for AMR, this meeting series is now in its 10th year and is being continued under the joint sponsorship of CARB-X, ESCMID, BEAM Alliance, GARDP, LifeArc, Boston University, and AMR.Solutions. The ongoing series will continue the successful format of prior meetings with a single-track meeting and substantial networking time (go here to see details of the outstanding 2024 meeting).
    • Registration is now open and the preliminary agenda can be found at that same link (https://www.gamric.org/). The meeting will be limited to approximately 300 attendees, so please be sure to register promptly to avoid disappointment! 
    • The abstract submission window (same link as registration) runs until 13 June.
    • Application for travel grants (same link as registration) are accepted through 2 June.
  • 19-22 Oct 2025 (Georgia, USA): IDWeek 2025, the annual meeting of the Infectious Diseases Society of America. Go here to register. For those who would like a substantial opportunity to present a product to a large audience (see also adjacent note about ESCMID), note the call for applications to present at an IDWeek Pipeline Session; go here to submit an application for your compound or diagnostic.
  • 3-4 Mar 2026 (Basel, Switzerland): The 10th AMR Conference. Sponsored by the BEAM Alliance, the 9th AMR Conference has just concluded and it’s again been an excellent meeting! Please mark your calendar for next year. You can’t register yet, but details will appear here! 
  • 17-21 April 2026 (Munich, Germany): ESCMID Global 2026, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. You can’t register yet, but you can go here for details on the outstanding 2025 meeting. For those who would like a substantial opportunity to present a product to a large audience (see also adjacent note about IDWeek), I know that the meeting schedule will again include Pipeline Monday; go here to see details from 2025.

  Upcoming meetings of interest to the AMR community:

  • [NEW] 22 July 202 (virtual, 9.30-11.00 CEST) Webinar entitled “Repurposing drugs to address the crisis of antimicrobial resistance”, organized by GARDP REVIVE. Go here to register. Recordings of prior REVIVE webinars are available for replay.
  • [NEW] 9 Sep 202 (virtual, 9.30-11.00 CEST) Webinar entitled “Overcoming challenges of tuberculosis drug discovery and development”, organized by GARDP REVIVE. Go here to register. Recordings of prior REVIVE webinars are available for replay.
  • 10-11 Sep 2025 (Ghent, BE): Organized by a group at Ghent University in collaboration with the ESCMID Study Group for Non-Traditional Antibacterial Therapy (ESGNTA), the Phage Protein Meeting is an interdisciplinary conference dedicated to advancing the field of phage proteins for infection control that seeks to bring together academic researchers and professionals working with phage proteins such as phage lysins, tail fibers, tailspikes, depolymerases, and tailocins. Note that the focus here is on phage proteins rather than phage themselves. Go here for details and to register.
  • 12 Sep 2025 (Ghent, BE): The 10-11 Sep 2025 meeting just above is followed in Ghent on 12 Sep by the 4th annual meeting of BSVoM (Belgian Society for Viruses of Microbes). This meeting is broader than therapeutics, providing an “interdisciplinary perspective on virus of microbes, ranging from basic research to industrial developments and clinical use.” Go here for details.
  • 10-13 Sep 2025 (Lisbon, Portugal): 6th ESCMID Conference on Vaccines. Go here for details.
  • 15-19 Sep 2025 (virtual): US CDC-sponsored the 9th Annual Fungal Disease Awareness Week (FDAW). Daily themed events include “Think Fungus” on 15 Sep, “Fungi are everywhere” on 16 Sep, and “Fungal diseases and drug resistance (19 Sep). Signup for the Mycotic Diseases Branch newsletter to stay updated.
  • 1-3 Oct 2025 GAMRIC, the Global AMR Innovators Conference (London, UK; formerly the ESCMID-ASM Joint Conference on Drug Development for AMR). See list of Top Recurring meetings, above..
  • 11-19 Oct 2025 (Annecy, France, residential in-person program): ICARe (Interdisciplinary Course on Antibiotics and Resistance) … and 2025 will be the 9th year for this program. Patrice Courvalin orchestrates content with the support of an all-star scientific committee and faculty. The resulting soup-to-nuts training covers all aspects of antimicrobials, is very intense, and routinely gets rave reviews! Seating is limited, so mark your calendars now if you are interested. Applications are being accepted from 20 Mar to 21 Jun 2025 — go here for more details.
  • 17-20 Sep 2025 (Porto, PT): 14th International Meeting on Microbial Epidemiological Markers (IMMEM XIV). Go here for details.
  • 9-13 Nov 2025 (Portland, OR, USA): ASM Conference on Biofilms. Go here for details and to register.
  • 18-24 Nov 2025 (global, multiple locations): World Antibiotic Awareness Week (WAAW) is convened annually on 18-24 Nov by WHO with national events (e.g., CDC’s US Antibiotic Awareness Week (USAAW); ECDC’s 18 Nov European Antibiotic Awareness Day) occurring around the globe. Details will follow as events become visible.
  • 19-22 Oct 2025 (Georgia, USA): IDWeek 2025. See list of Top Recurring meetings, above.
  • 29-31 Oct 2025 (Bengalaru, India): ASM Global Research Symposium on the One Health Approach to Antimicrobial Resistance (AMR), hosted in partnership with the Centre for Infectious Disease Research (CIDR) at the Indian Institute of Science (IISc). Go here for details and to register.
  • 28-30 Jan 2026 (Las Vegas, NV, USA): IDSA and ASM have announced a new US-based meeting series entitled IAMRI (Interdisciplinary Meeting on Antimicrobial Resistance and Innovation) and described as a “forum for collaboration and exploration around the latest advances in antimicrobial drug discovery and development.” You can’t register yet (further details anticipated June 2025) but you can go here to see general details about the new meeting.
  • 3-4 Mar 2026 (Basel, Switzerland): The 10th AMR Conference sponsored by the BEAM Alliance. See list of Top Recurring meetings, above.
  • 8-13 Mar 2026 (Renaissance Tuscany Il Ciocco, Italy): 2026 Gordon Research Conference (GRC) entitled “Antibacterials of Tomorrow to Combat the Global Threat of Antimicrobial Resistance.” A Gordon Research Seminar (GRS) will be held the weekend before (7-8 Mar) for young doctoral and post-doctoral researchers. Space for the GRS and the GRC is limited; for details and to apply, go here for the GRC and here for the GRS.
  • 17-21 April 2026 (Munich, Germany): ESCMID Global 2026, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. See Recurring Meetings list, above.
  • [NEW] 4-8 June 2026 (Washington, DC): ASM Microbe, the annual meeting of the American Society for Microbiology. The meeting format is evolving and next year will combine 3 meetings (ASM Health, ASM Applied and Environmental Microbiology, and ASM Mechanism Discovery) into one event. Go here for details.

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