RE: today's Ebola MCM working group

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

1. 2014-07-23 18:25 Jean Hu-Primmer open
   Dear Gary, Great call -- thanks for facilitating the discussions. I wanted to circle back with you and make sure I understand what FDA's current action item is with respect the outcome of our discussions. We are prepared to draft a document that is more generic with respect to regulatory considerations for Ebola therapeutics, and will also include some product-specific thoughts/recommendations. However, before we send that to you, we need to make sure that we invoke the PHEMCE MOU and have all participants of the WG sign the attached non-disclosure agreement so that we can share non-public information for the purpose of this WG's deliberations. Please see the attached document which is the PHEMCE MOU NDA "blessed" by ESC/EEC (if you need the actual MOU signed by all PHEMCE partners, please let me know). <<! ICC Form - 2014 PHEMCE MOU.PDF>> Also before we start the any discussion which will include non-public information, we need to state the following per the MOU SOP: "This discussion may include trade secret or confidential commercial information protected from disclosure to the public under the Freedom of Information Act, the Trade Secrets Act, the Federal Food, Drug, and Cosmetic Act, or FDA regulations. Each participant must have signed an individual PHEMCE Confidentiality Commitment to participate today, and information provided may only be shared with employees or contractors who sign a PHEMCE Confidentiality Commitment. Please identify yourself if you have not yet signed this agreement and we will provide one to allow for your continued participation today. Participants should not further disclose or otherwise make public the information that is shared." Finally, am happy to be the liaison for our FDA group, and appreciate that you go through me for all of your needs and concerns. One recommendation that our FDA group would like me to convey to you is that we strongly believe that NIAID/IRF should be included in the Ebola/Marburg MCM WG - specifically Lisa Hensley and/or her staff as they are engaged in much of the early research and even have boots on the ground in Africa and are in a position to share data that are critical to our deliberations. Thanks, Jean Casco, Tony (NIH/NIAID) [C]
2. 2014-07-23 20:46 Jean Hu-Primmer open
   FYI....see email below RE the non-disclosure agreement. To extent that we can provide any comments on the "frontrunner" MCMs indicated by our HHS partners including what data gaps need to be filled before we would consider use for US troops/CDC EIS officers and other US citizens in affected areas, that would be great. I understand that those MCMs are: 1. MappBio's ZMab 2. Toyama's T-705 3. Biocryst's BCX4430 4. Unither Virology's UV4 (which is listed in clinicaltrials.gov for a dengue therapeutic study) Any thoughts on these specific therapeutics would be great to include. Gary has already sent an email to the lead POCs of each agency/institution that says we cannot share our document until we have everyone who is participating in the WG sign off on the MOU's NDA. Rosemary - I passed on your suggestion of looping NIAID/IRF into the discussions; I hope they will comply. Thanks all for your participation and help in today's discussions!! Jean
3. 2014-07-24 07:51 Julian O Rear open
   Eric's document is not relevant here as there weren't any good candidate drugs for MERS-CoV so we were starting from square 1. I've attached my thoughts on the proposed candidates. Most of the information is in the public domain (links to references included). Jules O'Rear, Ph.D. Lead Clinical Virologist FDA\OMPT\CDER\OND\OAP\Division of Antiviral Products
4. 2014-07-24 09:09 Jean Hu-Primmer open
   FYI - Please take a look at the document Jules put together. I also asked them to include Tekmira after receiving this document. Please let me know if you know of anywhere we can get more information on the gaps Jules discussed - as well as if you have any questions which we should consider. Thanks!! Jean
5. 2014-07-24 10:07 Jean Hu-Primmer
   I will circulate your thoughts within the Division, as well as the excel spreadsheet -- see if they have any ideas. I will also ask Gary to consider convalescent IVIG since this Friday's conversation will be CBER-related and polyclonals are in their shop. I understand that because the field "hospital" conditions are very austere, there is a concern about the feasibility for any IV treatment with concerns of ancillary supply availabilitiy and potential for needlesticks etc.... was that raised during the WHO call? Thanks, Jean From: Olinger, Gene (NIH/NIAID) [C] [mailto J@nih.gov] Sent: Thursday, July 24, 2014 9:55 AM To: Hu-Primmer, Jean; Hensley, Lisa E (NIH); Honko, Anna N (NIH) Subject: RE: today's Ebola MCM working group Here are a few comments to consider: With unlimited funds, we would take as many "shots on goal" as possible, however, my experience is that there is limited funding and we will have prioritize. Anna made a wonderful comment the other day about rushing to use something that has potential too soon and killing it because of the rush! It is something we should all consider. Dr. Kobinger has demonstrated neutralization with two of the mabs in the cocktail and binding with all three mabs to the current isolate (unpublished, personal communication). The biggest issue past funding and time, will be scale up of the process to produce large lots of the drug (estimate 1-3 months). They are planning dose sparing studies in Sept. which could alter production and offer 2X, 5X or 10X production/doses numbers. That study could be expedited. BCX4430 has published data against Marburg and Ebola for guinea pigs but only Marburg virus for NHPs. Maybe there is unpublished data, but I expect (given my experience) there was less efficacy observed for EBOV versus MARV. It is also encouraging to see that the noted issues with toxicity, immune suppression, and high risk potential in phase I is listed for this product. I did see where NIH NIAID provided additional support for this product a few weeks ago. The recommendation for UV4 makes no sense as written. If UV4 is going to be listed, there really should be many other compounds listed that have demonstrated efficacy against Ebola in vitro, rodents, and in some cases NHPs. The work Lisa and Peter did with various drugs with efficacy should be considered. In addition, while at RIID we screened all of the approved drugs and there are many drugs that could be repurposed/given off-label with efficacy in mice (they are working on NHP studies; short list attached but many others). Most of the drugs I mention here are approved and could be given off label. We are also still missing vaccination. Both Dr. Sullivan's and the VSV platform should be considered as there are preclinical and clinical data available. The WHO has plans with the University of Geneva to use VSV (a cGMP lot) for those exposed and mabs for those that develop symptoms. Anna and I were on the telcon for Lisa the last few days with WHO. Would love to share some of the discussions. There was a lot of discussion on convalescent serum and how quickly a process could be developed to pursue that approach. Gene
6. 2014-07-24 11:39 unattributed open
   Honestly, at this point, cleaning the area is difficult. So there are many logistical/clinical issues. Injections, needles, etc. are an issue but IV is commonly done with Lassa cases (is how they administer ribavirin). Limited physical contact is preferred. In other conversations, oral administration is likely not ideal either as cases arrive late in disease and may not tolerate doses by oral route. Lisa or Anna may want to comment on this topic as this is a hotly debated area. May even want some of the clinicians who have been there or there to comment as I am sure there are local differences. Gene
7. 2014-07-25 10:13 Jean Hu-Primmer open
   Hotly debated here at FDA too -- this is part of the reason why DAVP does not want to comment on the already approved drugs for re-purposing because most are oral and they say that oral is not the way to go because as you say -- cases arrive late and will not tolerate oral doses. And we know that MSF is using IV therapies (ie |V rehydration)... Already approved drugs don't mean anything if we are changing route of administration of doses (because the some of the therapeutic windows are too narrow for EBOV).... If we change the dose or route the existing human safety information is questionable (may not be applicable).

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