Talk:Rintatolimod

Trials

There seems to be some disagreement between sources... [1] suggests that phase III clinical trials have been completed. while another part of their website [2] suggests they are currently enrolling, in agreement with the government clinical trials website, [3]. If anyone could shed some light on this, it would be welcome. Thedreamdied 17:47, 27 January 2007 (UTC)

The first link probably refers to the Phase III trial started in June 1997 (see e.g. http://www.cfids-me.org/cfscc/amptestimony.html). The other two links seem to refer to a different (new) study. FWIW... AvB ÷ talk 16:13, 28 January 2007 (UTC)

Yes, you are right. Thank you. Thedreamdied 18:04, 28 January 2007 (UTC

The entire Ampligen entry is incorrect and needs to be rewritten by a specialist —The preceding unsigned comment was added by Zanzibarlo (talk • contribs).

I agree. Which is why I have rewritten/reworked this entire wiki page and had the content reviewed and vetted by scientific experts in an attempt to improve the accuracy and quality of the information, including correcting broken and obsolete references. BluebirdHill5 (talk) 16:32, 4 April 2017 (UTC) Hemispherx Biopharma, Inc.

At what point does one concede that this company has been a huge fraud for many many years? It is now the end of the second quarter of 2007 and still no indication of when an NDA will be filed. Instead, we hear about a small flu trial in Australia. I will not even try to change web site but I think that the fact that this company is fraudulant, in my opinion, should be much more strongly emphasized. What if it is the Year 2010 and we still have no NDA submission?

The company is not a fraud and has experienced most of the main challenges that venture capital biotechs have encountered with FDA - that is, FDA is not well set up to work with these small, single product companies. A large corporation is already receiving income from old patents, a start-up company does not have that advantage, and the Phase III can be cumbersome and expensive. More to the point, the entire endeavor seems to be more focused on whether FDA will or will not "allow" the company to make money off of the drug - and not what we can learn from the drug right now. That is a generic problem, not specific to Hemispherx nor to those who would like to receive Ampligen and cannot get it because it requires proximity to a distribution site (you have to travel to twice-weekly infusions)- or because they don't have $20,000+ a year to spend on it. There is also ongoing debate as to whether the vaguely defined disease syndrome "CFS" should be the focus of the drug, or the specific biomarkers: 37kDa Rnase-L, HHV-6, CEBV, low natural killer cell count. When the biomarkers are used the rate of success is much higher than when questionnaires and treadmill tests are the sole determinants of who enters the study, and how well the study succeeds. Unfortunately, the Phase III was already well on its way before this became clear. Speaking for patients, we hope that FDA and Hemispherx can come to terms with the variations between patients in different sites, because those who did improve, and improved dramatically, have no substitute for the drug. ---- Alicesfriend

Dr. Schweitzer lost access to the drug in February, 2008, because the principal investigator at the practice where she received the drug died, and FDA required the submission of a new request for permission for an open-label study. The re-submission was rejected, and there is no site within a two hour radius to receive the drug. After having gone from a Karnovsky 30 (basically bedridden and requiring a wheelchair) to a Karnovsky 70 (needing daily assistance but able to walk, read, write, and drive), she is now sliding backwards into invalidism. ---- Alicesfriend —Preceding unsigned comment added by Alicesfriend (talk • contribs) 03:39, 18 September 2008 (UTC)

Expert Help

I feel that the entire 'Mechanism of Action' section is a bit confusing/weak and probably misleading/wrong. Perhaps you could help out? Thedreamdied 22:09, 29 January 2007 (UTC)

The entire Ampligen entry is incorrect and needs to be rewritten by a specialist. —The preceding unsigned comment was added by Zanzibarlo (talk • contribs).

OK i put in some mechanism stuff. I can put in the references, reviews i guess i will have to pick some. I am thinking some one can tell me more, how does this work, BC it says RNase L is elevated in CFS, that is causing the problems. Ampligen stimulates RNase L production, how does that help is it desensoritization or does any one know? I am curious now thx RetroS1mone talk 05:29, 9 January 2009 (UTC)

If you have access to full text try this review PMID 9243369. These are researchers that have published most on the subject in CFS. The problem as I know it is that excess low molecular weight 37 Kd RNase L (higher 37-Kilodalton/83-Kilodalton RNase L Isoform Ratio) found in CFS patients up-regulates the pathway. After Ampligen treatment the 37 Kd RNase L levels have been reported to be reduced. From there my knowledge is fragmentary. Ward20 (talk) 20:04, 9 January 2009 (UTC)

With the assistance of experts on Ampligen, I am attempting to provide helpful edits to this page in the section below called proposed changes. I will propose sections at a time until the page is updated in its entirety. BluebirdHill5 (talk) 14:48, 5 April 2017 (UTC) Hemispherx Biopharma, Inc.

With regard to User:Zanzibarlo and User:Zarzine

Blanking the article is unhelpful: and suggesting that "The entire Ampligen entry is incorrect and needs to be rewritten by a specialist" with the explanation "It was for the greater part incorrect, misleading and biased" is unhelpful - where is it incorrect, where is it misleading, and why is it biased? Feel free to correct any errors you see, with valid sources. Thedreamdied 23:12, 9 February 2007 (UTC)

With regard to User:Thedreamdied

Your contribution contains big mistakes (e.g. Ampligen phase III trial for CFS was completed in 2004, Bioclones' marketing rights are being challenged by Hemispherx Biopharma, Ampligen raw materials are no longer manufactured by Ribotech) and lacks relevant indispensable elements (e.g. the results of the phase II and phase III trials for Ampligen for CFS, relevant Ampligen patents)while containing a lot of irrelevant material (patent to infuse tobacco ). The serious side-effects you refer to lack correct evidence. The link you offer is a testimony of one person who cannot even prove that her problems were caused by Ampligen... I consider you lack the necessary competences and knowledge to write a serious article about Ampligen. It's a hopeless task to correct all the mistakes and the set-up of this entry, so someone should start from scratch.Wamper 11:12, 12 February 2007 (UTC)

Firstly, I agree that there may be some mistakes in the article - information on Ampligen is not readily available, it seems, and I will make the corrections you have outlined.

Secondly, you may class information as 'indispensable' but that does not neccessarily make it so - the article is not intended to be a list of every result for every clinical trial.

On the subject of the serious side effects in the section 'Impact', you are on reflection probably right. The evidence probably fails verifiability, and I will remove it.

However, to suggest that I 'lack the necessary competences and knowledge to write a serious article about Ampligen' somewhat misses the point of wikipedia - it is compiled by people who are not necessarily experts on what is written. Instead of being overly critical and unhelpful, it would be more useful if you were to constructively help in improving the article, making corrections where you feel they are necessary and adding relevant information.

Incidentally, I didnt add the bit about infusing ampligen with tobacco. Thedreamdied 13:21, 12 February 2007 (UTC)

Well, as I don't feel called upon to contribute, let me suggest you to compare the Wikipedia Ampligen entry with the information in the following fairly dependable research report http://www.boenningandscattergood.com/research/CI/HEB%20%282006.12.1%29.pdf and in the Sec filings of Hemispherx Biopharma http://www.sec.gov/cgi-bin/browse-edgar?action=getcompany&CIK=0000946644&owner=include As Ampligen is an experimental drug, I would wait for an EMEA European Public Assessment Report (EPAR) http://www.emea.eu.int/htms/human/epar/eparintro.htm or FDA equivalent Wamper 14:18, 12 February 2007 (UTC)

With regard to contributing

I have nevertheless tried to correct some errors and have added a number of useful references. The original entry was a blot on Wikipedia.Wamper 10:34, 13 February 2007 (UTC)

On the contrary, the original entry was, although relatively new, already a good Wikipedia article and shaping up to be a great one when you and your clones came along. The article had been built up from scratch almost singlehandedly by the editor whose work you are still putting down and obstructing by undue use of the Wikipedia AfD process. The same editor had just been put down personally, harassed, edit-warred and generally suffered from attacks by a string of single-use accounts. What makes matters worse is the possibility that User:Thedreamdied is probably a CFS patient, hampered in editing here by an intractible illness and looking forward to become a Hemispherx client if the drug is approved. As you may have noticed, all this has led to your and all of the other accounts being marked as possible sock puppets of the first abusive user. Currently you are not an editor in good standing. I could say more but I'll spend the time I intended to edit the article on bringing your recent edits up to Wikipedia standards.

Nevertheless, it is good to see you doing what many thousands of dedicated editors have been doing all along: making Wikipedia great by improving articles. I hope this means that you are discovering what makes Wikipedia tick and intend to do some real editing here. If so, you are most welcome. Please remember to make sure your edits adhere to WP:NPOV and other rules, and only (re-)introduce disputed edits after a consensus has been reached on the talk page. If you think an article, sentence or word introduces bias, all you have to do is discuss on the talk page and where necessary use our WP:DR process, e.g. bringing in uninvolved editors to make sure the consensus process is working and the rules are being followed. AvB ÷ talk 12:38, 13 February 2007 (UTC)

PS You have already demonstrated that you can initiate an AfD. Do you think you, as the nominator, are up to closing the AfD in keeping with the relevant rules and procedures? The result of the AfD is, obviously, a Speedy Keep. I'll also try to find an uninvolved editor with a mop but it would be simply excellent if you took up the chore. AvB ÷ talk 12:51, 13 February 2007 (UTC)

I have given it the try, please check it out, as I'm not sure it is OK.Wamper 13:23, 13 February 2007 (UTC)

Thanks, looking at it now. AvB ÷ talk 13:31, 13 February 2007 (UTC)

Citations

For all citations, a separate entry in the References section is required. I added one citation with a template as footnote, but maybe you prefer to stick with embedded citations, in which case the references need to be added separately another time. Tikiwont 10:32, 14 February 2007 (UTC)

Please review WP:CITE for information on how to include inline citations in articles. The 'references' section is for inline citations. If you want to add extra titles that are not cited by the article text, they would go in a 'further reading' section. Dr. Cash 00:41, 27 February 2007 (UTC)

Asensio etc

I'm not sure its really that relevant to the article to have so much about it. Perhaps a 'Hemispherx Biopharma' article could be created, with an explanation of their controversial history? Thedreamdied 14:46, 14 February 2007 (UTC)

I think the fortunes of Ampligen are likely to be closely tied up with ALL the obstacles it has met on its way. So we should not forget one. But feel free to cut down the Asensio story if you think it is too wordy.Wamper 10:44, 15 February 2007 (UTC)

Likewise, the fortunes of Hemispherx are likely to be closely tied up with the fortunes of Ampligen. Normally I would say that a separate company article is a good idea, but I'm not so sure in this case. The story of Ampligen is the story of Hemispherx. For now I've created two Hemispherx redirect pages. AvB ÷ talk 11:31, 15 February 2007 (UTC)

Perhaps, but Hemispherx have other drugs, some of which i put on wikipedia, such as Alferon LDO, which are now ignored by the redirect to this article. Thedreamdied 14:24, 15 February 2007 (UTC)

Generally, if the articles on the separate products would be small, we tend to write a single article on both the company and its products, redirecting the drug names to the main article. But you're right, I thought they only had Ampligen and Ampligen-derived Oragen. Since Alferon is clearly unrelated to Ampligen, it may indeed be useful to start a separate HEB article. I think we have sufficient content regarding the drugs themselves to warrant separate articles. AvB ÷ talk 14:50, 15 February 2007 (UTC)

Ampligen and HIV

According to here, Ampligen is mainly for CFS as well as HIV, which is barely mentioned in the article. AMP 720 is listed here, and there seems to be quite a lot of info available generally. Thedreamdied 15:39, 14 February 2007 (UTC)

Neutral point of view

This article seems to be the subject of competing points of view, particularly in the "Controversy" section. If there are any knowledgeable, yet uninvolved, editors that could help check this article for adherence to Wikipedia's neutral point of view policy, that would be helpful. -- Ed (Edgar181) 16:56, 29 June 2009 (UTC)

It seems ok to me. I did right it, of course, but it seems to present information reasonably fairly. Thedreamdied (talk) 11:39, 2 July 2009 (UTC)

It's hardly neutral

"In June 2009, The Street alleged..." "The Street also alleged"

references to an individual Asensio is biased representing him as a reputable person whereas, he has been barred "from association with any NASD member in any capacity" ref: http://en.wikipedia.org/wiki/Manuel_P._Asensio "Asensio & Company has issued a research report on Hemispherx that contains a Strong Sell and Short Sell rating." ref: http://www.aegis.com/NEWS/PR/1999/PR990509.html

So there's no neutrality this entire section is being hijacked by persons of opposing views and could be rewritten with an unbiased taint and accurate references pertinent to "AMPLIGEN" —Preceding unsigned comment added by 97.101.138.235 (talk) 23:54, 10 July 2009 (UTC)

It is hijacked?? Anon hijacks and does BLP and accuses someone they are not reputable. That is personal attack, BLP problem. Do you want, the article should say "The Street proved" or what is it?? I do not understand, i do not like BLP problem and I agree on Thedreamdied, it is neutral. I remove the tag. RetroS1mone talk 03:48, 14 August 2009 (UTC)

Marketing?

Ward20 changed the lead from 'refused to approve' to 'refused marketing approval', but that doesn't seem to be what the source says. It just says they refused to approve it for treatment of CFS. --sciencewatcher (talk) 22:55, 12 February 2010 (UTC)

Sorry, evidently my edit summary was poor, I should probably have explained it better on the talk page. Adam Feuerstein's article[4] was a little sloppy in his first sentence in that he didn't mention specifically that the FDA's refusal was for Ampligen's New Drug Application (NDA). The philadelphia bizjournals source I added clarifies the refusal was for the NDA.[5] The NDA is concerned with marketing approval of the drug, not experimental usage. The Ampligen NDA was filed in 2007. (See page three, last paragraph of Feuerstein's article[6] and the Press Release - NDA filing of Ampligen for CFS for verification. A different FDA approval process called Investigational New Drug (IND) (the step before NDA marketing approval) is concerned with experimental usage of Ampligen. There are no statements the IND usage for Ampligen is affected, and the sources state that the FDA wants Hemispherx to do more clinical studies, which would be regulated under IND approval. Ampligen never had retail marketing approval, only experimental studies approval (including open label), and the FDA decision doesn't change the status quo. Ward20 (talk) 00:16, 13 February 2010 (UTC)

I've tweaked it a bit. I removed the marketing bit because it's more than just marketing - it is for sale to the public. Saying they were refused marketing implies incorrectly that they just aren't allowed to advertise it. And because we already mention the NDA application in the previous sentence, I just added the rejection to the same sentence. I also added the reason (lack of proven efficacy), as that is important. --sciencewatcher (talk) 16:15, 13 February 2010 (UTC)

Changes look good. I added "to market and sell Ampligen" to further address your concerns. Ward20 (talk) 19:11, 13 February 2010 (UTC)

LOL. I just noticed you already made the same changes to the Chronic fatigue syndrome treatment article so I guess we are on the same page. Ward20 (talk) 19:18, 13 February 2010 (UTC)

Proposed deletion

Google scholar gives 1350 hits for Ampligen in (and 80 for Rintatolimod) excluding patents and refs. This seems plenty to establish that this is actually a notable substance, whether or not the current refs are any good. JMiall₰ 16:27, 15 April 2015 (UTC)

External links modified

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Proposed Article Changes

Intro: These proposed changes has been rewritten/reworked and the content reviewed and vetted by scientific experts in an attempt to improve the accuracy and quality of the information, including correcting broken and obsolete references. As noted in various sections of this talk page, this page is in need of expert help, the page contains statements that are not really useful about rintatolimod, and some information that is incorrect and/or biased.

I propose the following changes. The current text proposed for deletion has been italicized. My comments are in CAPS. The new text is in regular font. If the proposed edits are approved, I will/can re-post the approved information in the wiki page and cite the references. Once this first section is reviewed, I have additional content to add I believe will be equally beneficial to this wiki page. I believe this new language is informative and provides useful information where the current page is a bit of a mess.

Introduction:

1ST AND 2ND PARAGRAPHS OF CURRENT TEXT TO BE DELETED: Rintatolimod, sold under the tradename Ampligen, is a medication intended for treatment of chronic fatigue syndrome.[1] However, there is only low-quality evidence that it can improve the ability to exercise.[1]- Reason for deletion: the second sentence if factually incorrect. If you read the article referenced, it clearly does not come to this conclusion and does not state this.

It is an immunomodulatory double stranded RNA drug synthesized in the 1970s and manufactured by Hemispherx Biopharma.[2]

Although Ampligen was cleared for use in Canada in 1997,[3] and obtained orphan drug status for treatment of CFS in the European Union in 2000,[4] it is so far without FDA approval, and therefore classed as experimental in the United States. In 2007, Hemispherx filed a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) to market and sell rintatolimod for the treatment of CFS,[5] but this was rejected in December 2009, because the FDA concluded that the two RCTs "did not provide credible evidence of efficacy"[6][7] and "because of clinical, statistical, clinical pharmacology, nonclinical, product quality, and facilities inspection deficiencies."[8] The FDA requested Hemispherx conduct at least one additional controlled trial to demonstrate efficacy in treating CFS. In August 2012, Hemispherx submitted further analyses of the original clinical trial data, but did not submit additional trials for review. Four months later, a committee of the FDA voted 8-5 against approval for rintatolimod, again citing insufficient data.[8]

THE CURRENT TEXT ABOVE IS TO BE REPLACED WITH THE FOLLOWING:

Rintatolimod (brand name Ampligen®) is a mismatched double stranded RNA (dsRNA). Rintatolimod activates Toll-Like Receptor 3 (TLR3), which results in transitory modulation of the cellular expression of hundreds of genes providing initial innate immune responses. Innate immunity provides initial resistance against invading viral pathogens and the later adaptive immune responses responsible for long term immunity. Among the genes responding to rintatolimod are the interferons (IFN) known to provide broad antiviral and growth inhibitory properties (Ref). Rintatolimod activates IFN induced proteins that require dsRNA for activity (e.g.- 2ʹ-5ʹ adenylate synthetase, protein kinase R). Rintatolimod’s gene inducing activity is limited to activation of TLR3 (restricted TLR3 agonist), which minimizes systemic inflammatory cytokine responses (see mechanism of action below).

The branded product, Ampligen®, is owned and manufactured by Hemispherx Biopharma, Inc.[2](Ref)The properties of clinical grade rintatolimod and a molecular model of the activated rintatolimod:TLR3 dimer complex are summarized in Table 4.[1] Intellectual property for rintatolimod includes new form and substance patents in the US and Europe.[2]

BluebirdHill5 (talk) 20:57, 4 April 2017 (UTC) Hemispherx Biopharma, Inc. BluebirdHill5 (talk) 19:02, 16 June 2017 (UTC)

Hi BluebirdHill5, and thank you for your suggestions. I am not convinced that the information about lack of FDA approval should be removed from the lead. Therefore, I am declining this edit request. Nor do I agree that the second sentence in the existing paragraph should be removed: perhaps "low quality" is an imprecise term, so I replaced it with "low strength", which is exactly the term the article cited uses to describe the evidence on Rintatolimod's effectiveness. Altamel (talk) 03:03, 26 June 2017 (UTC)

References

User:BluebirdHill5 thanks for bringing this to talk. I agree this does not appear to be an improvement thus support it not being implemented. Doc James (talk · contribs · email) 17:43, 26 June 2017 (UTC)

Argentina approval

This drug has been approved in Argentina for chronic fatigue syndrome (might just be severe Chronic fatigue syndrome). I added it on the CFS page but it got reverted due to the sources used and I can't find better ones. Perhaps someone here can find better, either way posting here to make you aware of content that may be worth adding. I believe overall the evidence isn't great for that particular use. Limited sources below.

• Nasdaq news
• FDA letter (a download)
• book p310

Amousey (talk) 15:04, 27 May 2020 (UTC)

Mention of Argentina is back in the lead, with source used Globe News Wire, which posts the manufacturer’s statement of status in Canada (special use program) and approval in Argentina, as of 2016, Amousey. I hope that source suffices. I can look for more sources, perhaps an Argentine newspaper article? - - Prairieplant (talk) 22:55, 17 May 2021 (UTC)

I added a second source re Argentina. - - Prairieplant (talk) 00:05, 18 May 2021 (UTC)

Thanks User:Prairieplant - I have only just seen this. Further sources below, including for Turkey and the EU, largely thanks to pandemic drug articles. PMC7104317: "Rintatolimod is the only drug to have completed successful advanced placebo-controlled clinical trials (Phase II/III) for ME/CFS and is approved for severe ME/CFS in Argentina." PMC8277229: "Currently approved for ME-CFS only in Argentina, the drug is given by twice weekly infusions. The Food and Drug Administration (FDA) permits these treatments on a compassionate use basis in the United States. However, the drug is available in only two locations: Incline Village, Nevada or Charlotte, South Carolina." PMC7930332:

Needs updating

I just updated url and formatted sources in the lead section, and marked a few dead links. I added copy re Canada and Argentina. I updated the official web site for Hemispherx in the lead as well. Lots of the refs are used only in the lead, which is not best form for Wikipedia. The lead is meant to highlight the article’s contents, so the refs ought to be somewhere in the article as well. I might copy a section of the lead into a new section on Status across the world. I am not usually editing articles on drugs, and do not know if there are special rules, like for the articles on diseases.

Lots of references in the main body of the article are dead links today, but I have no more time just now to hunt for updated links. I can share that FDA has its own search page for archived links. Follow the link in the article, get the FDA page saying “we cannot find this”, go their archive page and insert the old url in search bar, click to search archive and see what you get. If you get a usable url, then keep the old url in the ref and add the new one as archive-url and add the archive-date, provided on the FDA page.

Sources provided on this page here might improve this article. I had no idea that Ampligen was still in use, and was quite pleased to find this article. I hope it can get updated further and cleaned up a bit. - - Prairieplant (talk) 23:10, 17 May 2021 (UTC)

The ref name fda1 was apparently used more than once in the article and needs clearing up. It generates an error message. - - Prairieplant (talk) 00:07, 18 May 2021 (UTC)