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Re: I could use some help from "old-timer" Tekmira folks regarding TKM-Ebola data... HCWs versus patients etcThanks, ego. I do now see from a couple of presentations on Tekmira's site that data has been discussed for the 3rd gen TKM-Ebola: See for example, the presentation given on May 21st: http://files.shareholder.com/downloads/ABEA-50QJTB/3343724105x0x756577/0d33620f-ba63-4edb-81e6-cd638e973389/MacLachlan_ASGCT_2014.pdf And I do believe I've seen some discussion of this on the board here... I don't see any mention of a delayed treatment test (as has been the case with Marburg), but I do see a test showing 100% efficacy w/ 0.5 mg/kg dose and 67% efficacy w/ 0.2 mg/kg dose (each given over 7 daily doses) It also presents Phase 1 clinical data, showing max tol. dose of 0.3 mg/kg, and plans to go forward in the MAD study with a max dose of 0.24 mg/kg. ~~~~~~~ A few things I want to note from the recent ZMapp study that saw 100% effectiveness when dosing was begun up to 5 days past infection. (And a big thank you to Cave In Temptor's post showing the data - http://www.investorvillage.com/smbd.asp?mb=11383&mn=20384&pt=msg&mid=14131189) As Cave In Temptor pointed out, the only treatment dosing regimen they used was 3 doses of 50 mg/kg 3 days apart. And they did so for NHPs given a huge viral dose (2512 PFU), which showed 100% survival in dosed starting as far as 3 days out. ...and for NHPs given a much less viral dose (628 PFU), which showed 100% survival starting as far as 5 days out. ~~~~~~~ (FYI: from the various studies I've seen of Tekmira's, a viral dose of 1000 PFU seems to be standard - and is what ZMapp gave in their 2012 studies. So Tekmira hasn't tested against the very high viral dose, nor the very low viral dose, that ZMapp recently tested against. In Tekmira's Marburg NHP studies, which showed 100% survival when NHPs were given treatment 3 days out, for all we know, it might have been the same with a much higher dose too; further, it might have seen 100% survival 5 days out if given a much lower dose (628 PFU) - we just don't know; and we don't yet know what TKM-ebola might show with delayed studies, although the Marburg results bode well, at least that's what others, like Geisbert, have said. Also, I can't quite tell if TKM-Marburg is using 3rd gen tech or not, at least at time of testing for the 3 days post injection. Anybody know if Tekmira was using 3rd gen LNP tech for that?) ~~~~~~~~ Something we DON'T know for ZMapp's recent study... They used a very high dosing regimen (3 - 50mg/kg doses 3 days apart) to achieve the 100% survival rate. But we don't know yet what a max tolerated dose would be in humans. (Does anyone know the dose given to patients in the current outbreak? I can't find that, but if anyone else can, that'd be great to know) As we have found out, the max tolerated dose in humans for TKM-Ebola is not the 0.5 mg/kg that was used in the NHPs that saw 100% efficacy, but rather 0.3 mg/kg. And as ego said, that may work out quite well in humans. But Tekmira needed to find out what the max tolerated dose was in safety trials. ~~~~~~~~ So that's something that still needs to happen for ZMapp - to find max tolerated dose. And it looks like that's the plan... to go through safety trials in humans before proceeding further with patients in W. Africa. I've seen that mentioned in the following two articles: http://www.latimes.com/science/la-sci-sn-ebola-drug-zmapp-saves-monkeys-20140829-story.html Robin Robinson, director of the federal agency that procures drugs and vaccines for public health emergencies, said through a spokeswoman that enough of the drug was expected to be available by the end of the year to conduct a Phase 1 clinical trial to test the safety of ZMapp. Other companies that can produce drugs in tobacco will be enlisted, said Dr. Robinson, whose agency, the Biomedical Advanced Research and Development Authority, is part of the Department of Health and Human Services. He said that there was debate about how quickly to deploy the drug in Africa but that officials thought it was important to test the safety in healthy volunteers first. ~~~~~~ And in this one: http://www.latimes.com/science/la-sci-sn-ebola-drug-zmapp-saves-monkeys-20140829-story.html "We hope that initial safety tests in humans will be undertaken soon, preferably within the next few months, to enable the compassionate use of ZMapp as soon as possible," they added. ~~~~~~ Also, in that just quoted from article, I appreciated what it said about what they were seeing in the monkeys both 3 days out and 5 days out, which goes along with what ego wrote in his post about health care workers being excellent candidates for receiving treatment, as they are both more cognizant of what symptoms might arise; plus, there also going to be @ or near a treatment center when they notice symptoms... This bodes well for being able to start treatment of health care workers around 3 days post infection: Most of the monkeys were evidently ill as early as three days after infection -- they had begun to eat and drink less and become feverish, and the virus was detectable in their blood. By day five, their symptoms were "more pronounced," said Kobinger. ~~~~~~ Linda |
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Msg # | Subject | Author | Recs | Date Posted |
20481 | Re: I could use some help from "old-timer" Tekmira folks regarding TKM-Ebola data... HCWs versus patients etc | latebloomer | 0 | 9/1/2014 3:33:14 PM |