Free at last of one fearfull diseases and devastating weapons (Smallpox)

[Snowy Owl]

I would like to express my Gratitude to our Mod Anne from France

Antimicrobial Agents and Chemotherapy, May 2008, p. 1721-1727, Vol. 52, No. 5

0066-4804/08/$08.00+0 doi:10.1128/AAC.01303-07

Copyright ? 2008, American Society for Microbiology. All Rights Reserved.​

Single-Dose Safety and Pharmacokinetics of ST-246, a Novel Orthopoxvirus Egress Inhibitor​

Robert Jordan,1 Deborah Tien,1, Tove' C. Bolken,1 Kevin F. Jones,1 Shanthakumar R. Tyavanagimatt,1 Josef Strasser,2 Annie Frimm,3 Michael L. Corrado,3 Phoebe G. Strome,3 and Dennis E. Hruby1*
SIGA Technologies, Corvallis, Oregon,1 TransTech Pharma, Inc., High Point, North Carolina,2 INC Research, Raleigh, North Carolina3

Received 9 October 2007/ Returned for modification 24 January 2008/ Accepted 23 February 2008​

ST-246 is a novel, potent orthopoxvirus egress inhibitor that is being developed to treat pathogenic orthopoxvirus infections of humans.

This phase I, double-blind, randomized, placebo-controlled single ascending dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of ST-246 in healthy human volunteers.

ST-246 was administered in single oral doses of 500, 1,000, and 2,000 mg to fasting healthy volunteers and 1,000 mg to nonfasting healthy volunteers.

ST-246 was generally well tolerated with no serious adverse events, and no subject was withdrawn from the study due to ST-246.

The most commonly reported drug-related adverse event was neutropenia, which was found, upon further analysis, not to be treatment related.

ST-246 was readily absorbed following oral administration with mean times to maximum concentration from 2 h to 3 h.

Absorption was greater in nonfasting volunteers than in fasting volunteers.

Administration of ST-246 resulted in exposure levels predicted to be sufficient for inhibiting orthopoxvirus replication compared to exposure levels in nonhuman primates in which ST-246 protected animals from lethal orthopoxvirus infection.

* Corresponding author. Mailing address: SIGA Technologies, Inc., 4575 SW Research Way, Corvallis, OR 97330. Phone: (541) 753-2000. Fax: (541) 753-9999. E-mail: dhruby@sgph.com
Published ahead of print on 3 March 2008.

Present address: Baxter Healthcare Corp., Thousand Oaks, CA.

http://aac.asm.org/cgi/content/abstract/52/5/1721

For full text cf to http://aac.asm.org/cgi/content/full/52/5/1721

Abstract can be found at http://aac.asm.org/cgi/content/abstract/52/5/1721

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons

Re: Free at last of one fearfull diseases and devastating weapons

any relevance for influenza ?

(orthomoxyvirus)

 

[Giuseppe]

Re: Free at last of one fearfull diseases and devastating weapons

Re: Free at last of one fearfull diseases and devastating weapons

any relevance for influenza ?

(orthomoxyvirus)

Poxvirus are DNA viruses and Orthomyxovirus are RNA viruses.
Smallpox viruses are large viruses and several agents seem to reduce their activity.
For example, DNA viruses such as Herpesvirus are inhibited by Acyclovir but no same result can be obtained if used against seasonal flu.

 

[Snowy Owl]

Re: Free at last of one fearfull diseases and devastating weapons

Re: Free at last of one fearfull diseases and devastating weapons

Smallpox, labs sequences and potentially being in the hands of people not recommandable is now getting out of a very major concerns about WMD.

This is a major news and a very good one.

Snowy

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

so ... the relevance to influenza could be that some funding from
smallpox will be transferred to influenza

(or vice versa ?)

 

[tropical]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

so ... the relevance to influenza could be that some funding from
smallpox will be transferred to influenza

(or vice versa ?)

The relevance of posted threads of other illness is gained from the existing FT forum item box place:

Emerging & Other Health Threats (12 Viewing)
Sub-Forums:

Seasonal Flu 2007 - 2008,

Maps & Charts,

Pregnant and Nursing Mothers,

Childhood Diseases,

Elderly Disease Issues,

Current Threats,

By Region,

Adenovirus 14,

Alcoholism,

Cancer,

Chagas Disease,

Chandipura Virus,

Cholera,

C. dificile,

Dengue,

Diarrhea,

Ebola,

Encephalitis,

Food Safety,

HIV/AIDS,

Kala Azar/Leishmaniasis,

Malaria,

Meningitis,

MRSA,

Nipah Virus,

Norovirus/Norwalk,

Polio,

Other respiratory diseases,

Rift Valley Fever,

SARS,

Tuberculosis,

Tularemia,

Typhoid,

West Nile Virus,

World Hunger,

Yellow Fever

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

...which however is subject to discussion as the article itself.

OK, I conclude that this study doesn't increase the hope for
panflu treatment.

 

[mixin]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

I don't understand the difference between this one and what we currently have in stock?

In the exercise: Dark Winter, it took at least 4 weeks to make more vaccine; would this one be produced quicker? If that's the case, let's hope the next 2 phases are as successful as the first.

I found Dark Winter to be very unsettling. I can see the quandary our govt might be in when it comes to how much money should be spent on a viral pandemic. As we are currently seeing, disasters come in many forms.

Repeatedly, hospitals are overwhelmed and the grid goes down.

 

[mixin]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

Biosecurity Briefing

Acambis Wins USG Contract for Smallpox Vaccine
By Kunal Rambhia, April 25, 2008

On April 23, 2008, Reuters reported that British vaccine developer Acambis won a $425 million, 10-year contract to supply the United States government with 9 million doses of the ACAM2000 smallpox vaccine each year for delivery to the Strategic National Stockpile (SNS). The contract may be increased to $660 million if the U.S. Centers for Disease Control and Prevention (CDC) opts to increase the order to 39 million doses in the fifth year.1

According to the article, the contract values ?each dose at an average of $3.96 over the course of the contract.? In the past, CDC purchased 195 million doses of the vaccine for the SNS from Acambis at $1.95 per dose, before it was approved by the Food and Drug Administration (FDA) last August. On April 25, The Telegraph reported that manufacturing of the vaccine under the new contract is required to take place in the U.S.2

http://www.upmc-biosecurity.org/web...mallpox/2008-04-25-acambisusgsmallpoxvac.html

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

uhh, $425M !!! That's more than they spent on prepandemic (flu-) vaccine !


Is it available for privates ? Do we have to add smallpox-vax to
our preps ? What says the government ? Do they encourage/
require private prepping for smallpox attacks ?

Is it only for USA ? I haven't heard about other countries to
file contracts for smallpox vaccine. Are there WHO-statements ?

 

[Snowy Owl]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

Thw usual vaccine is not needed anymore with this new medication,

As for Fku-treatment gs, I still believe that the peptides has more potential than we anticipated, that was told to me on phone by Mike Perdue in Geneva.

Mingus would be able to explain it better than me, but he is mobilised in his woek and his family.

Snowy

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

the $428M would be spent invain ?
Can/will they cancel it ?

what peptides ?

 

[Giuseppe]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

While new compounds discovery is welcomed, one might use a bit of caution while stating about amazing properties of this drug. Smallpox virus is extint, and coltures only survives in labs. Vaccines are the best gun in our arsenal and were succesflully used in the past to achieve pox eradication.
However, same tools serving to drug discovery purpose may be useful in more precious compounds scanning for other viral illness treatment that pose an impending threat to worldwide population.
In addition, as the antimicrobial history is teaching us, resistant agents evolve everytime a drug is used against them.
Perhaps, the story of the neglected NA inhibitor peramivir may also be of interest as non-public health concerns' influence drugs development and approval for clinical use.

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

you mean: Snowy can't be trusted and he uses exaggerating
headlines to mislead us ? ;-)

(like most others do)

 

[Giuseppe]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

I'm not at all. I say only that there are distinct opinions about this news. US and other countries are in full right to spend their resource as they like, with the aim to protect citizens from the threats they think could happen.
I hope only that same techonology used to discover the compound for poxviruses will be also useful for further viral inhibitors scanning.

 

[Snowy Owl]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

Gs, on top of this when the US order the vaccines it was the sole thing that had reliable effects.

The Smallpox problems has stated by Ironorehopper is the fact that it exist in labs only and as you know sometimes bad people try to get these bad strain and trying to make the devastating weapons.

I do not know the terms of the contract made by US and I will search from Pasteur the timeframe of production of the new medication, but if I was a gov deciders I would have done the same as US and would now consider this new option.

One thing is sure now, in the medium term the smallpox threat as a wepaon has reduced and remember that was a scary threat for quite awhile.

Snowy

 

[mixin]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

Perhaps, the story of the neglected NA inhibitor peramivir may also be of interest as non-public health concerns' influence drugs development and approval for clinical use.

I think it was wise of BioCryst to do another Phase ll study. Hopefully, the results will enable them to go on to Phase lll. If the 300mg dose can be proven safe, it would be much better to have one 300mg injection in pandemic times than to have to get 2 of 150mg. They also want to try doses higher than 300mg in this trial.

http://www.biospace.com/news_story.aspx?NewsEntityId=83699

 

[Giuseppe]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

I think it was wise of BioCryst to do another Phase ll study. Hopefully, the results will enable them to go on to Phase lll. If the 300mg dose can be proven safe, it would be much better to have one 300mg injection in pandemic times than to have to get 2 of 150mg. They also want to try doses higher than 300mg in this trial.

http://www.biospace.com/news_story.aspx?NewsEntityId=83699

I would only remind that peramivir was for a while an 'orphan' drug. One may search into the web for more detailed information about initial trails and subsequent withdrawal and more other interesting things pertaining in general for new drugs R&D (other than NA inhibitors, in effect).

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

Snowy, that contract was from 25.Apr.2008, at that time they should have
known/anticipating something about this ST-246

Received 9 October 2007/ Returned for modification 24 January 2008/ Accepted 23 February 2008



> Free at last of one fearfull diseases and devastating weapons (Smallpox)
I have doubts.Else they won't spend $428M

> remember that was a scary threat for quite awhile.
I don't remember. Not in Europe.

 

[gsgs]

Re: Free at last of one fearfull diseases and devastating weapons (Smallpox)

OK, I searched a bit and found:

---------------------------------------------
Combined HHS and DHS Biodefense preparedness spending:
FY 2001 -- $294 million [HHS budget]
FY 2002 -- $3 billion [HHS budget]
FY 2003 -- $4.4 billion [combined HHS and DHS budgets for Biodefense]
FY 2004 -- $5.2 billion [combined HHS/DHS - incl. BioShield proposal]
---------------------------------------------

compare this with the panflu budget ("half of mankind could die")
of $7 billion for 2006-2008 (3 years).

Now, what do you think they consider the bigger threat ?

Of, course, this is all minute when you compare it with what they spent for
protection from Iraq's non-existing WMDs ...



does it make sense ?