Final FDA LPAD guidance: Same substance, useful clarifications

Dear All,

FDA have released the final version of their LPAD (Limited Population Pathway for Antibacterial and Antifungal Drugs, really should be LPPAAAD) guidance. You can get it here. I have generated a comparison with the Jul 2018 draft version that you can get here.

As a reminder, the central concept of the LPPAAAD pathway (OK, so I like the extra letters … sing it aloud to appreciate the melisma!) is that “FDA’s determination of safety and effectiveness take into account the severity, rarity, or prevalence of the infection a drug is intended to treat and the lack of alternative treatment in the limited population for which the drug is intended.”

Specifically, “FDA may approve a drug under the LPAD pathway based upon a conclusion of a positive benefit-risk balance in the limited population, even though insufficient data exist to conclude that there is a favorable benefit-risk profile in a broader population” because “drugs with risks that would be unacceptable for a broad population may be acceptable for patient populations with serious diseases that do not have other treatment options.”

The final LPAD guidance doesn’t offer anything really new (nor was that expected), but there are some useful clarifications:

  • A drug can have both LPAD and non-LPAD indications (Section III, definition of LPAD): “There may be cases when a drug is approved under the LPAD pathway for certain indications and may be approved under a non-LPAD pathway for other indications.  The labeling will make clear the indications approved under the LPAD pathway (see section VII., Conditions for Approval Under the LPAD Pathway).”
  • The use has to be in a limited population (Section III.A.2): “For example, an antibacterial drug that would have a role in the preventive armamentarium for only a select patient population (e.g., mechanically ventilated patients) with no other options may be an appropriate candidate for the LPAD pathway; in contrast, an antibacterial drug intended for broad population-level prevention of an infrequently or rarely occurring serious or life-threatening disease generally would not be an appropriate candidate for the LPAD pathway.”
  • LPAD isn’t for all drugs (Section V): “If an applicant submits a request for approval of an application under the LPAD pathway, but the drug instead can be approved under the traditional approval pathway or the accelerated approval pathway alone, FDA will approve the application, but not under the LPAD pathway.  For example, a drug for which the sponsor conducts a streamlined development program may be eligible for traditional approval if the clinical data support approval in a broader population.”


It’s great to have this final guidance on LPAD and I hope to see more use of it in the future. If you want to dig deeper into LPAD, follow these links:

  • Per discussions at this week’s antifungal R&D workshops, only two drugs have thus far used the LPAD pathway: Arikayce (link) and pretomanid (link).
  • See also this wonkish note (link) from FDA’s 12 Jul 2019 Public Meeting on the LPAD pathway in which I’ve further explored the history of LPAD.


All best wishes, –jr

PS: Superb article yesterday on CARB-X by Maryn McKenna in the Boston Globe Magazine — read it here! Thank you, Maryn, for working to tell the story so clearly for our non-technical colleagues!

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:

  • Novo REPAIR Impact Fund closed its most recent round on 31 Jul 2020. Go here for current details.
  • 2020 funding rounds for CARB-X have not been announced.
  • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes funders and projects by geography, stage, and more.


Upcoming meetings of interest to the AMR community:

  • 7 Aug 2020 (online, 3-7.30p BST): The Longitude Prize Sprint Workshop entitled “Navigating MedTech Regulation Pathways in Developed and Emerging Markets”. Register here for this deep-dive into regional variations in the rules for devices.
  • 17 Aug 2020 (online, 1-2.30p EST): ASM Microbe 2020, Industry & Science program. Go here for details.
  • 24-28 Aug 2020 (online, 9.45a-18.30p CEST daily): BEAM Alliance-sponsored AMR Conference. Go here for details.
  • 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.
  • 9-10 Sep 2020 (Washington, DC): US PACCARB public meeting. Go here for details.
  • 21-25 Oct 2019 (online meeting), IDWeek 2020. Go here for details.
  • 26-29 Oct 2020 (online meeting), Annual ESPID meeting (European Society for Pediatric ID, #38)
  • 27 Oct 2020 (online meeting), BARDA Industry Day, a discussion of U.S. Government medical countermeasure priorities. Mark your calendar now and watch this website for details.
  • 10-13 Apr 2021 (Vienna): Annual ECCMID meeting (#31)
  • 18-21 May 2021 (Albuquerque, New Mexico): Biannual meeting of the MSGERC (Mycoses Study Group Education and Research Consortium). Save-the-date announcement is here, details to follow.
  • 20-24 June 2021 (Toronto): International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-12). Go here for details.
  • 3-7 Jun 2021 (Anaheim), ASM Microbe 2021. Go here for details.
  • 27 Jun-2 Jul 2021 (Ventura, CA): Gordon Research Conference entitled “Antimicrobial Peptides”. Go here for details, go here for the linked 26-27 Jun Gordon Research Seminar that precedes it.
  • 5-21 Aug 2021 (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.
  • 8-11 Oct 2021 (Aberdeen, Scotland): 10th Trends in Medical Mycology. Go here for details.
  • 16-24 Oct 2021 (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. Registration is here and is limited to 40 students.
  • 6-11 Mar 2022 (Il Ciocco, Tuscany): Gordon Research Conference entitled “New Antibacterial Discovery and Development”. Go here for details, go here for the linked 5-6 Mar Gordon Research Seminar that precedes it.

Share

Share on twitter
Share on facebook
Share on linkedin
Share on email
Share on whatsapp
Share on reddit

Consultancy: Sustainability framework for off-patent antibiotics // The Third Man

Dear All, I have just learned that the AMR Industry Alliance has posted an RFP for a consultant to support the work of its Access Working Group with applications for the RFP due 24 September 2021. The consultancy project focuses on the root causes of (or lack thereof!) supply chain resilience for off-patent antibiotics, including stockouts, shortages

Outstanding discussions of Pull, the NHS Pilot, and Antibiotic value

Dear All, The BEAM Alliance, along with its partners (CARB-X, the Novo REPAIR Impact Fund, the IMI AMR Accelerator, and the European Biotechnology Magazine) converted their annual AMR conference into a virtual event held 24-26 Aug 2021. As usual, it was excellent! I know we’re all really, REALLY tired of virtual meetings but the 2h/day x 3 day themed format worked well:

WHO-FAO-OIE-UNEP survey on a multi-stakeholder AMR platform

Dear All (this newsletter experiments with an Executive Summary/Details format; let me know what you think),  (Executive Summary)  As a further support for implementation of recommendations from the UN Interagency Coordination Group on Antimicrobial Resistance (IACG AMR), the Tripartite Plus (WHO-FAO-OIE-UNEP) are seeking to create a Partnership Platform that will “engage institutions representing states, markets and

“Astonishing mismatch”: Market potential of AMR tools vs. patient needs

Dear All, We have today an excellent report from the Global AMR R&D Hub entitled “Estimating Global Patient Needs and Market Potential for Priority Health Technologies Addressing Antimicrobial Resistance.” Both the bottom line and the key message of the report are clearly stated in the Preface: “… we hope that by showing the astonishing mismatch

Scroll to Top