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

Impact of PASTEUR: 9.9m lives saved, ROI of 125:1

Impact of PASTEUR: 9.9m lives saved, ROI of 125:1 Dear All (and with thanks to Kevin Outterson for being lead author on this newsletter), (wonkish alert on this one … refresh your coffee and dig in!) The Center for Global Development have released a blog post and a paper estimating the potential impact of the PASTEUR Act.

Five FDA RFPs! Antifungal animal models, MIC breakpoints, and more!

Dear All, I just today learned that FDA have posted their FY 2023 funding opportunities. All the details are on this webpage and I’m just going to reproduce the text below my signature for your reference. I’ll also add a few details in italics. Lots of good opportunities here! –jr John H. Rex, MD |

WAAW! Must-Read Article, A Quiz, A Video, A Call to Action

Notes: Newsflash … BARDA have opened their long-running BAA-18-100-SOL-00003 to include support for antifungal agents. Search for “antifungal” in the posted .pdf to find the text. The first deadline for proposals is 15 Dec 2022 and further deadlines will doubtless follow: as shown on page 9, this BAA has offered 4 deadlines/year since 2018!  Dear All, In

Fireside Chat with AMR Action Fund CIO Martin Heidecker

Dear All, Ahead of World Antimicrobial Awareness Week, I sat down with AMR Action Fund Chief Investment Officer Martin Heidecker for a Fireside Chat. It was a fabulous conversation that covered everything from how the Fund’s investment process works to what it’s looking for in portfolio companies to broader investment trends in the AMR space.  As

Scroll to Top