Talk:Ampligen

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Contents 1 Trials 2 Expert Help 3 With regard to User:Zanzibarlo and User:Zarzine 4 With regard to User:Thedreamdied 5 With regard to contributing 6 Citations 7 Asensio etc 8 Ampligen and HIV 9 Ampligen Disease Targets - Mentioned by HEB over the Years

[edit] 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).

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?

[edit] 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).

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] 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)

[edit] Ampligen Disease Targets - Mentioned by HEB over the Years

HEB Proposed Ampligen Uses Per Company Press Releases, Interviews and Patent Applications

1. Bioterrorism Rapid Response Tool (June 2006) 2. Myocarditis 3. HIV/AIDS 4. HHV-6 5. CFS/ME 6. Small Pox 7. SARS 8. Avian Flu - when combined with the neuraminidase inhibitors Oseltamivir, (brand name Tamiflu) and with Zanamivir (Relenza) (June 2007) 9. Hepatitis B 10. Hepatitis C 11. West Nile Virus 12. Common Flu (Carter Quote March 2006) (As a vaccine adjunct) 13. Monkey Lung Inflammation (June 2006) 14. Renal Cell Carcinoma 15. Malignant Melanoma 16. Ebola 17. Gulf War Syndrome (January 1997) 18. Equine Encephalitis Virus (October 2003) 19. Dengue Fever virus (October 2003) 20. Japanese Encephalitis Virus (October 2003) 21. Coxsackie Virus 22. Multiple Sclerosis (Carter 1995) 23. With DOGS [not the animals] - Vaccine Technology Platform (VACCINE ENHANCE) – [This is a “refinement/enhancement” of proposed Use Number 1] 24. Lung Cancer (1987 – via Tobacco) 25. Emphysema (1987 – via Tobacco) 26. Chronic Obstructive Pulmonary Disease (1987 – via Tobacco) 27. Vascular Disease (1987 – via Tobacco) 28. Tobacco Mosaic Virus infection (1987 on the Tobacco itself) 29. Kidney Cancer (1998) 30. Alzheimer's Disease (1999 – Patent No. 5958718) 31. Arthritis (1995 - United States Patent 5683986) 32. Tuberculosis (Ampligen with AZT – 1996 presentation) 33. Septic shock subsequent to trauma, burns, surgery, transfusion, radiation therapy or chemotherapy (US Patent 5763417 - Year 1995). Diseases Identified in 1995 Patent Application to be treated via topical cream or condom coating 34. Herpes Simplex 35. Herpes Zoster 36. Cytomegalovirus or CMV (sometimes classified as a herpes-type virus) 37. Localized skin cancer with and without vital etiology 38. Susceptible sexually transmitted viral conditions and venereal infections including Chlamydia 39. Venereal infections in which the causative viral agent is primary or secondary to another venereal infection itself insensitive or less than adequately controlled by mismatched dsRNA which secondary infection is being treated by another therapeutic modality (such as a concurrent gonorrheal infection for which the patient is receiving tetracycline therapy).

ALL CAN BE VERIFIED BY WEB SEARCHES.

HEB NDA PUBLIC SERVICE FILING GUIDANCE (Part 1)

HEB NDA Filing Guidance – 2004 http://sec.edgar-online.com/2004/03/22/0000891092-04-001352/Section9.asp Assuming the results are positive, we expect to finalize the data of our double-blind, placebo controlled AMP516 ME/CFC Phase III clinical trial and submit an NDA by year end 2004.

HEB NDA Filing Guidance 2005 –Early 2006 http://sec.edgar-online.com/2006/01/03/0000946644-06-000001/Section4.asp The single shortfall of our 2005 objectives was the delay in the filing of our NDA for Ampligen(R) for the treatment of CFS. Our targeted filing by 2005 year-end was based on an anticipated grant of FDA permission to submit a rolling or staged NDA application, which would allow us to file the safety and clinical sections of the NDA application in advance of the manufacturing section. Even though FDA permission to submit a rolling or staged NDA application has yet to be received, since we are scheduled to complete our manufacturing certifications late in the 2nd quarter of 2006, we should, in any event, file our NDA for Ampligen(R) for the treatment of CFS no later than the first part of the 3rd quarter of 2006.

HEB NDA Guidance November 7, 2006 http://www.pharmalive.com/News/Index.cfm?articleid=389255

The year-over-year increase in loss of $1,164,000, primarily reflected a combination of factors including 1) an increase of $215,000 in manufacturing costs, especially in connection with a production ramp-up and the preparation of an NDA filing for the Company's experimental drug Ampligen(R) to treat Chronic Fatigue Syndrome, with that filing expected by the end of this calendar year or the first quarter of calendar 2007

HEB 10-Q November 7, 2006 http://biz.yahoo.com/e/061107/heb10-q.html We continue our efforts with respect to preparing a New Drug Application ("NDA") for submission to the Food and Drug Administration ("FDA") for using Ampligen(R) to treat patients afflicted with Chronic Fatigue Syndrome ("CFS"). The preparation of the NDA is a time consuming and laborious process….. We have experienced technical teams assigned to preparing each of these three segments. When completed these three technical documents will be consolidated into the common technical document for submitting to the FDA. While the results of our AMP 516 Phase III clinical study is the basis for filing the NDA we must also include the safety data collected on all patients that ever received Ampligen(R) (some 800 patients from clinical trials for CFS, HIV, Hepatitis, cancer, etc.) All of this is time consuming as our clinical monitors and research assistants must visit and audit the records of clinical investigators involved in our Ampligen clinical studies conducted over the last 15 years.

Note: On November 6, 2007, Dr. Carter was awarded a pay raise retroactive to January 1, 2006.

CONFERENCE CALL November 15, 2006

HEB filing to be INITIATED by December 31, 2006.

HEB Investor E-mail Re: BOENNING & SCATTERGOOD.INC Initial Coverage (12/4/2006) - We anticipate an NDA filing no latter than the first quarter of 2007. (Spelling error in press release.)

http://www.boenningandscattergood.com/news/news_view.asp?ID=31 Note: Web site says NDA filing will be SOON!

HEB NDA PUBLIC SERVICE FILING GUIDANCE (Part 2)

Roth Conference in Dana Point – February 22, 2007 – Dr. Carter Presentation The filing of the NDA will be completed by the end of the first quarter of 2007. Acceptance of the NDA filing is expected by the end of the second quarter of 2007.

March 19, 2007 10-K Filing

http://www.sec.gov/Archives/edgar/data/946644/000114420407013492/v068807_10k.htm The NDA is being filed electronically to facilitate the ease of review by the FDA. We cannot yet provide guidance as to the tentative date at which the compilation and filing of the NDA will be complete, as significant factors are outside our control including, without limitation, the ability and willingness of the independent clinical investigators to complete the requisite reports at an acceptable regulatory standard, the ability to collect overseas generated data, and the ability of Hollister-Stier facilities to interface with our own New Brunswick staff/facilities to meet the manufacturing regulatory standards. However, the overall process is proceeding. We started the NDA registration process on December 29, 2006 with the filing of one of the three major required sections. The timing of the FDA review process of the NDA is subject to the control of the FDA and could result in one of the following events; 1) approval to market Ampligen® for use in treating ME/CFS patients, 2) require more research, development, and clinical work, 3) approval to market as well as conduct more testing, or 4) reject our NDA application. Given these variables, we are unable to project when material net cash inflows are expected to commence from the sale of Ampligen®.

PHILADELPHIA BUSINESS JOURNAL - March 30, 2007 by John George, Staff Writer

Hemispherx BioPharma Inc. is finalizing its new drug application for Ampligen, an experimental treatment for chronic fatigue syndrome that has spent more than 30 years in clinical studies.

Dr. William Carter, the Center City biotechnology company's chairman and CEO, said he expects the application will be completed in early April.

HEB CONFERENCE CALL – May 1, 2007

Dr. Carter says that HEB is working with the FDA to answer questions regarding the filing. He states the filing is complex and cannot give a timetable as to when the NDA will be filed.

HEB NDA PUBLIC SERVICE FILING GUIDANCE (Part 3)

SEC 10-Q Filing – May 10, 2007

http://www.sec.gov/Archives/edgar/data/946644/000114420407023929/v074337_10q.htm

We started the NDA process on December 29, 2006 with the filing of one of the three major required sections. Subsequently, we have filed various other portions of the application with the FDA for comment and suggestions. As is customary, the FDA reviewers have asked for various clarifications in certain areas and additional information in various other areas including preclinical sections, chemistry/manufacturing sections and medical sections. Our staff and two retained Clinical Research Organizations (CROs) have been actively working to respond to the various queries, including conducting additional clinical exams and lab testing. While this process may delay the finalization and completion of the NDA, we feel that in the long run it may accelerate an effective review process. The application is also being expanded in certain sections such that it may be simultaneously suitable for filing in certain other countries. Finally, as a result of the lengthy regulatory history of Ampligen®, certain early non-CFS studies (such as those in HIV/AIDS, hepatitis and thermal injury) are requiring extensive reprogramming of archival data for inclusion in the application to meet current FDA requirements. In contrast, the CFS medical reports are substantially complete and the company plans to submit the CFS medical reports at the same time that the archived studies have been reprogrammed.

The NDA is being filed electronically to facilitate the ease of review by the FDA. We cannot yet provide guidance as to the tentative date at which the compilation and filing of the NDA will be complete, as significant factors are outside our control including, without limitation, the ability and willingness of the independent clinical investigators to complete the requisite reports at an acceptable regulatory standard and the ability to collect overseas generated data.

May 14, 2007 Monte Carlo, Monaco Presentation (Slide Show)

HEB targets the fourth quarter of 2007 to announce "completion of responses and semi-final responses concerning on-going FDA review of the NDA program."

SEC 10-Q Filing – August 9, 2007

http://www.sec.gov/Archives/edgar/data/946644/000114420407041455/v083541_10q.htm

We have filed certain sections of our Ampligen® NDA with the FDA for review and comment. As expected, the FDA reviewers have requested clarification in some areas and additional information in certain pre-clinical, chemistry, manufacturing and medical sections. We have engaged the services of additional Clinical Research Organizations (CROs) to assist in the responding to the various inquiries as well as conducting additional clinical exams and lab work. We have also added additional research personnel to assist the CROs. These personnel have experience at major pharmaceutical companies, i.e., J&J, Merck and GlaxoSmithKline. As previously reported, this process is affecting the finalization and completion of the NDA. We believe that in the long run, it may accelerate the review process; however, we cannot offer guidance on when the NDA will be deemed complete or when the review will be completed.

October 10. 2007 through December 3, 2007

HEB filed an NDA on October 10, 2007. On December 3, 2007, the FDA deemed the NDA submitted by the company on October 10, 2007 to be incomplete. Specifically, eleven deficiencies were noted in the Clinical Section and three in the Pre-Clinical Section.

http://www.sec.gov/Archives/edgar/data/946644/000094664407000006/0000946644-07-000006.txt

HEB NDA PUBLIC SERVICE FILING GUIDANCE (Part 4)

December 10, 2007 Conference Call

Dr. Carter says that HEB will respond to all NDA questions, submit responses to the FDA and have a meeting by mid-February 2008. He says that the FDA comments include the following concerns:

• Data organization • Statistical analysis anomalies with the treadmill test trial end points • Potential cardiac affects of Ampligen • Missing data files regarding patients

Dr. Carter remarks that the firm, while transparent, should have hired a “Table of Contents” subconsultant.

December 12, 2007 – Bonelli Presentation

COO Bonelli claims that “amendments” to the NDA will be filed before the end of 2007 and that a meeting with the FDA will likely be scheduled in February 2008 to discuss the amendments to the application.

No announcement regarding any filing of “amendments” was made by the end of 2007. Meanwhile, the following bonuses were awarded to HEB management as announced 12/31/2007:

“The Board of Directors of Hemispherx Biopharma, Inc. (AMEX:HEB - News) announces that, on December 26, 2007, certain executives were awarded bonuses of 25% of base salaries for performance in relation to 2007 corporate goals and objectives. Bonuses were awarded to W.A. Carter, M.D., CEO and Chairman of the Board ($166,156), Anthony Bonelli, COO ($87,500), Robert Peterson, CFO ($64,791), Dr. David Strayer, Chief Medical Officer ($50,347) and Wayne Springate, V.P. of Manufacturing ($37,500).”

January 9, 2008 – Press Release

Hemispherx Biopharma, Inc. (AMEX:HEB - News) announced today that it has formally submitted to the United States Food & Drug Administration (``FDA) detailed responses to all of the 14 questions posed by the FDA concerning the Company's New Drug Application (``NDA) for Ampligen(r), an experimental therapeutic, to treat Chronic Fatigue Syndrome (``CFS). Hemispherx received the questions from the FDA on December 5, 2007, at which point the application was deemed by the FDA as ``not sufficiently complete to permit substantive review under 21 CFR 314.101(R). Consequently, the FDA's consideration of the NDA was postponed, pending receipt of the Company's answers to the questions.

Late February 2008

Note: HEB claims it met with the FDA on February 8, 2008 to discuss the NDA application. (Source: COO Bonelli at Disney Conference.)

HEB NDA PUBLIC SERVICE FILING GUIDANCE (Part 5)

Philadelphia, PA, March 6, 2008---Hemispherx Biopharma, Inc. (AMEX, HEB) announced today that, following its submission of a clarifying amendment on January 9, 2008, to its NDA application and a subsequent face-to-face meeting with the Agency, the number of items necessary to accomplish a complete NDA for filing purposes has been reduced from an original fourteen (14) to five (5). Specifically, for NDA filing purposes, 9/14 of the original incomplete items noted in FDA letter received December 5, 2007 are no longer considered filing – related issues. The remaining open items are being promptly addressed by the Company thru a series of five (5) additional Amendments to its NDA as described below.

Specifically, the open items-requisite for a complete NDA filing status - may be grouped into one of two categories: Category (1) Administrative items (four) include: (a) transfers of additional clinical records (termed “CRF’s”), (b) transfer of several documents previously submitted to the FDA, (c) additional clinical data reconciliations (compiled from the CRF records) and (d) additional computer generated charts which summarize specific parts of the CRFs. Transfer of these records will thereby allow the Agency reviewers to evaluate independently the statistical efficacy /safety conclusions of the Company’s existing NDA. Category (2) (One item): a reformatting and enlarged analysis of the existing pharmacokinetics (“PK”) report to more closely align with current International Committee on Harmonization (“ICH”) guidelines.

Importantly, the company believes no further studies are required to achieve a complete NDA filing status for purposes of regulatory review of the entire document.

As part of the agreement reached with the Agency, the additional files/data may be submitted sequentially as separate NDA Amendments to the existing NDA to accelerate the review process. Submission of these Amendments to the FDA is expected to begin this week with all Amendments expected to be completed and filed shortly. A collaboration with Octagon Research Solutions, a major provider of electronic filings of regulatory documents, will facilitate and accelerate the overall filing process. These Amendments will add to the overall data base of the existing NDA (submitted October 10, 2007) and the company’s pre-submission of non-clinical information (submitted December 29, 2006), which was assigned the original NDA number.

While the company is optimistic as to the progress of the NDA filing, there are no assurances that the FDA will accept the amended NDA for review, and if accepted there are no assurances that the NDA will be approved.

April 9, 2008 Conference Call

Carter says he expects the remaining five NDA filing “deficiencies” to be addressed in the next several weeks and then expects that it will take the FDA about 8 weeks to determine if the NDA application is now acceptable for review. The new target date for the acceptance of the application would be the end of May 2008 or June 2008, doing the math. Carter takes questions regarding the delays and problems and states that many of the problems are the result of the FDA’s increased scrutiny in accepting trial data.