Retrovirus Positive CFS Patients Show Enhanced Response to Ampligen(R), an Experiment

George

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My bolds here but I thought this was pretty cool

http://www.marketwatch.com/story/hemispherx-biopharma-to-present-new-retrovirus-xmrv-data-at-1st-international-workshop-on-xmrv-and-chronic-fatigue-syndrome-cfs-2010-09-08?reflink=MW_news_stmp


Sept. 8, 2010, 10:23 a.m. EDT Recommend Post:
Hemispherx Biopharma to Present New Retrovirus (XMRV) Data at 1st International Workshop on XMRV and Chronic Fatigue Syndrome (CFS)
Retrovirus Positive CFS Patients Show Enhanced Response to Ampligen(R), an Experimental Therapeutic, Relative to XMRV Negative Group

BETHESDA, Md., Sep 8, 2010 (GlobeNewswire via COMTEX) -- Hemispherx Biopharma, Inc. /quotes/comstock/14*!heb/quotes/nls/heb (HEB 0.55, +0.00, +0.22%) will present new clinical data on the possible inter-relationships of XMRV positivity/chronic fatigue syndrome/Ampligen(R) responsiveness at the 1st International Workshop on XMRV being held at the National Institutes of Health in Bethesda, MD, on September 7 and 8, 2010.

CFS is a severe disorder consisting of profound fatigue and a variety of other debilitating symptoms that affects up to 4 million Americans. Recently, DNA was identified from a human gamma retrovirus (XMRV) in 67% of CFS subjects. Evidence also suggested that approximately 50% of the CFS subjects mounted a specific antibody response against XMRV (Science 326, 585-589 (2009)). The objective of this study was to compare demographic parameters and health/performance status of XMRV antibody positive vs. negative CFS subjects enrolled in a Phase III clinical trial evaluating the safety and efficacy of a toll-like receptor 3 agonist, rintatolimod (PolyI:polyC12U, Ampligen(R)). The response to Ampligen(R) with regard to the primary endpoint, treadmill exercise tolerance testing (ETT), in this population was also evaluated.

Two-hundred-eight (208) evaluable subjects, who met the original (1988) and revised (1994) Centers for Disease Control criteria for CFS, participated in this randomized, placebo-controlled, double-blinded, multicenter study. Only severely debilitated patients with a Karnofsky Performance Scale between 40-60 were selected for this study. The primary endpoint was exercise treadmill duration. Subjects received Ampligen(R) (200-400 mg) or an equivalent volume of placebo (saline) twice weekly by intravenous infusion for 40 weeks. Baseline (or earliest available specimen) serum samples from all 208 subjects were analyzed for antibodies directed against XMRV.

The XMRV antibody positive cohort had a greater relative percentage of subjects showing a >25% increase in ETT with Ampligen(R) treatment compared to placebo than the XMRV antibody negative cohort. The results also suggest that the XMRV antibody negative subjects with CFS have a lower activity level and a reduced ability to complete normal daily activities at baseline. If validated as a relevant basis for targeting the XMRV positive CFS patient sub-population, the observed response advantage of the XMRV may translate into needing a smaller sample size for future research using a placebo-controlled parallel design to obtain 80% power (α=0.05): 216 XMRV antibody positive subjects vs. 330 XMRV antibody negative subjects. Additional studies to further evaluate XMRV in this CFS population are currently underway.

About Hemispherx Biopharma

Hemispherx Biopharma, Inc. is an advanced specialty pharmaceutical company engaged in the clinical development of new drug entities for treatment of seriously debilitating disorders. Hemispherx's flagship products include Alferon N Injection(TM) (FDA approved for a category of sexually transmitted diseases) and the experimental therapeutics Ampligen(R) and Alferon LDO(TM). Ampligen(R) represents experimental nucleic acids being developed for globally important debilitating diseases and disorders of the immune system. Hemispherx's platform technology includes agents for potential treatment of various severely debilitating and life threatening diseases. Hemispherx has an extensive number of patents comprising its core intellectual property estate and a fully commercialized product (Alferon N Injection(TM)). The Company wholly owns and exclusively operates a GMP certified manufacturing facility in the United States. For more information, please visit www.hemispherx.net

Information contained in this news release, other than historical information, should be considered forward-looking and is subject to various risk factors and uncertainties. For instance, the strategies and operations of Hemispherx involve risk of competition, changing market conditions, change in laws and regulations affecting these industries and numerous other factors discussed in this release and in the Company's filings with the Securities and Exchange Commission. Any specifically referenced investigational drugs and associated technologies of the Company (including Ampligen(R) and Alferon(R) LDO) are experimental in nature and as such are not designated safe and effective by a regulatory authority for general use and are legally available only through clinical trials with the referenced disorders. The forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements. The planning, completion, results or submission of clinical trials do not imply that any study product will ever be approved commercially for the studied or other treatment indications.

This news release was distributed by GlobeNewswire, www.globenewswire.com

SOURCE: Hemispherx Biopharma, Inc.

CONTACT: Hemispherx Biopharma, Inc.
Company/Investor Contact:
Dianne Will
518-398-6222
ir@hemispherx.net
 

dannybex

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"The XMRV antibody positive cohort had a greater relative percentage of subjects showing a >25% increase in ETT with Ampligen(R) treatment compared to placebo than the XMRV antibody negative cohort. The results also suggest that the XMRV antibody negative subjects with CFS have a lower activity level and a reduced ability to complete normal daily activities at baseline."

XMRV-negatives had a LOWER activity level, etc.? Isn't that the exact opposite of what we've been hearing?
 

Nina

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XMRV-negatives had a LOWER activity level, etc.? Isn't that the exact opposite of what we've been hearing?
I was asking myself that very question.

Also, only about 50% showed antibody response? I thought we were assuming the AB test would show a positivity rate of >67%?
 

gu3vara

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Could mean those infected severely don't even have an antibody response to the virus, just a thought. It's possible that people who got the virus really early in life don't even have a immune system that consider the pathogen as an invader.

I think we cannot say they are XMRV negative for sure yet.
 

Daffodil

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During the Science paper study, there were some in whom they found XMRV but no antibodies. However, detection methods are superior now so I don't know if this still holds.

I wonder if this will make the FDA finally approve Ampligen.
 

pine108kell

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I actually find this disturbing. There are hints that those that are XMRV- (and it looks like there will be plenty) will be left in the dark ages--and maybe these are the sickest.
 

Esther12

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I actually find this disturbing. There are hints that those that are XMRV- (and it looks like there will be plenty) will be left in the dark ages--and maybe these are the sickest.
If XMRV works out I think it will be good news for everyone, and lead to more honest resarch being done into CFS generally, including those who are negative.
 

Impish

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Just because they are XMRV -ve doesn't mean that they are MuLV -ve necessarily. It could be that whatever detection they used for this didn't pick up the MuLV CFS patients.
 

dannybex

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I was asking myself that very question.

Also, only about 50% showed antibody response? I thought we were assuming the AB test would show a positivity rate of >67%?
But keep in mind, that study was quite small, only 101 patients. Seems to me Dr. Lombardi said (around March or April?) that about 50% of the test results had come back positive (from patients who had paid for testing).

I have no idea, but am thinking that Hemispherx screwed up somehow w/their press release.

???
 

dannybex

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If XMRV works out I think it will be good news for everyone, and lead to more honest resarch being done into CFS generally, including those who are negative.
I think so too. People have recovered or are at least getting better, even if it's very rare. Dr. Klimas has mentioned patients of hers who have completely recovered. Hopefully Cort can interview her about that in the future.
 

calzy

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I think so too. People have recovered or are at least getting better, even if it's very rare. Dr. Klimas has mentioned patients of hers who have completely recovered. Hopefully Cort can interview her about that in the future.
Gotten better how?

you mean in the past or currently?
 

dannybex

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Klimas: "remission...and complete resolution..."

Gotten better how?

you mean in the past or currently?
She was quoted in an interview from 2008:

"Q: Doctor, do you believe in remission of the illness?

Dr. Klimas: Absolutely! And complete resolution! It happens, but not often enough to make promises. I get the best hugs on airplanes and other public places when I bump into patients now healthy and happy."

http://www.prohealth.com/library/showarticle.cfm?libid=13462

p.s. The "how" is going to be different for each patient. Depends on their triggers, their environment, genetics, etc.....
 

BEG

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The more we learn, the less we know . . . Please just fix my brain so I can understand the science that is unfolding.
 

Hope123

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You know, I'm very suspicious of anything coming out from Hemispherix; I'd like to see the details also.

What does more than 25% increase in exercise tolerance testing mean? Is it duration on the treadmill with no payback? Increased V02 max? Does 25% translate to anything meaningful? It sounds good but say your v02 max was 10 and it increased to 12.5.................this is still way below normal and I am not sure if this would translate to anything a person would notice.

Also, Hemispherix never mentions adverse effects. If there are no adverse effects, it would benefit them to write something like "there were no serious side effects noticed" or "only mild side effects occurred." The equation patients/ doctors have to balance when deciding on treatment is not just whether a treatment is potentially beneficial but also whether a treatment could potentially make someone worse.
 
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I was very confused when I read the Hemispherix report but after reading several more times I think I understood what they were trying to say. The patients that are XMRV+ were able to increase their exercise capacity while the XMRV- were less able to exercise. They were showing the drug was more effective in XMRV+ patients.
 

Francelle

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A couple of things strike me about this study!

It must have been started VERY soon after the Science article was published in early Oct 2009 – which is about 48 weeks ago. The subjects in this cohort were taking the Ampligen or placebo for 40 weeks – which means to me, if I am reading this correctly, as well as taking into account the compilation of results, that it was a speedily set up study!

How can they do it so fast? Usually with IRB’s and all the other protection of study participant rigmaroles, it takes months to set up a good study – leave alone get the study cohort!

The other thing they talk about is XMRV antibody positive/negative subjects but back 40 + weeks ago how well defined was XMRV antibody testing – or were they already sophisticated for lab usage?

I may be wrong on all this though!!
 

garcia

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Interesting points by francelle.

People seem to be interpreting this result as saying if you are XMRV positive you are more likely to respond to ampligen. However that is not my interpretation.

My interpretation is that people who were producing antibodies are presumably healthier than those unable to mount an antibody response. This interpretation also fits in with:
"The results also suggest that the XMRV antibody negative subjects with CFS have a lower activity level and a reduced ability to complete normal daily activities at baseline."
Do we seriously believe that having XMRV makes you more likely to have a higher activity level and an increased ability to complete normal daily activities? Of course not. The only logical explanation therefore is that the antibodies are a proxy for how sick you are (assuming most of the CFS patients in the cohort have xmrv).

Take home message: Antibodies are a reflection of how well your immune system is working, therefore how sick you are (the sickest may not produce antibodies). People who are sicker may respond less well to ampligen than those who are less sick (within a given time-frame).
 

JohnnyD

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Francelle,

This was not a new trial, this was a blood re-sampling of HEB's Phase III trial, completed in 2006 I believe.