Released by FDA: 7/7/00.  Posted by FDA:  7/17/00

William A. Carter, M.D. 
Chief Executive Officer 
Hemispherx Biopharma, Inc. 
One Penn Center 
1617 JFK Boulevard 
Philadelphia, PA 19103

RE:   AMPLIGEN (POLY I:POLY C12U) 
         MACMIS #8800

Dear Dr. Carter:

This letter concerns materials disseminated by Hemispherx Biopharma, Inc. (Hernispherx) for its product, Ampligen, which is an unapproved new drug and the subject of an Investigational New Drug Application (IND) with the Food and Drug Administration (FDA).  The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed these materials as part of its routine monitoring and surveillance program.  From its review, DDMAC has concluded that Hemispherx is promoting Ampligen as safe and effective prior to approval, in violation of the Federal Food, Drug, and Cosmetic Act (Act) and its implementing regulations.

BACKGROUND 
Ampligen is an investigational new drug manufactured by Hemispherx Biopharma, Inc. The generic name of Ampligen is poly I:poly C12U.  Hemispherx has indicated that it intends to develop Ampligen for the treatment of individuals with human immunodeficiency virus (HIV) and Chronic Fatigue Syndrome (CFS).

We previously issued an untitled letter, dated October 15, 1998, to Hemisphcrx for promoting Ampligen as safe or effective while the product was under investigation.  In our letter, we informed you that your activities were in violation of the Act and applicable regulations.  In your response, dated October 29, 1998, you assured us that Hcmispherx would discontinue or revise all materials concerning Ampligen to conform with the Act and regulations.

However, notwithstanding your assurances, you continue to promote Ampligen as safe and effective prior to approval in your press releases and on your Internet website. Such activities constitute promotion of an investigational new drug as safe or effective in violation of the Act and its implementing regulations.  In addition, your promotional materials are false or misleading in that they fail to disclose facts that are material in light of representations made about Ampligen.

PRESS RELEASES 
Hemispherx promotes Ampligen as safe and effective in several press releases.  In addition, Hemispherx fails to reveal facts that are material in light of representations made about Ampligen.

Safety 
In press releases, Hemispherx promotes Ampligen as “generally well tolerated” or “well tolerated” but fails to disclose risk information associated with the use of Ampligen.  For example, in your press release dated February 17, 2000, entitled “Hemispherx Files for HlV Emergency Treatment IND and Phase II/III Trials,” you state, “To date, Ampligen has been studied in 126 patients and has been consistently well tolerated in its trials.”  However, toxicities that have been reported in dose-escalating studies of Ampligen in HIV-infected patients include, but are not limited to, flushing, chills, fever, chest tightness, nausea, malaise, shortness of breath, flu-like symptoms, leukopenia, neutropenia, and leukocytosis.

Effectiveness 
In your February 22, 2000 press release, you present that, “. ..Ampligen demonstrated synergistic activity with anti-retroviral therapy leading to potential enhanced suppression of replicating HIV virus....”  Similarly, in your press release of December 16, 1999, entitled  “Hemispherx Announces New Approach to HIV Multi-Drug Resistance,” you state, “...multiple HlV genetic mutations that made the 14 anti-HIV drugs approved by the Food and Drug Administration (FDA) ineffective did not diminish the pronounced anti-viral effectiveness of Ampligen.”  These statements make conclusions concerning the effectiveness of Ampligen, an investigational new drug, in violation of the Act and its implementing regulations.

INTERNET WEBSITE 
Although some of the materials referenced below were originally issued by third parties, this letter does not concern the third parties or their original communications.

Your website, www.hemispiherx.com, contained a direct link to transcripts of Dr. Mazien’s CFS Radio Program, which promote Ampligen as safe or effective.  For example, the linked transcript from Dr. Mazien’s CFS Radio Program from February 28, 1999, presents the following conversation between Dr. Mazien and Dr. Paul Cheney:

Further, your website is directly linked to a web page containing anecdotal reports of CFS patients who participated in clinical trials.  For example, on the “Other CSF Links” page on your website there is a link entitled, “The ‘Ampligen 511 Panel’ Patients Speak About Their Experiences with Ampligen at the AACFS Conference.”  The link goes directly to the patient testimonials that are located at www.cfids-me.org.  These patient testimonials promote Ampligen as safe or effective prior to approval.  The following statements are examples of patient testimonials:

Lastly, your website also contains press releases, including but not limited to those previously described, that promote Ampligen as safe or effective.

REQUESTED ACTIONS 
Hemispherx should immediately cease dissemination of materials or activities that contain these and similar claims, representations, and conclusions concerning the safety or effectiveness of Ampligen.  In addition, Hemispherx should respond in writing no later than July 21, 2000 describing its plan to comply.  Hemispherx should also include a list of materials being discontinued, as well as the date of discontinuation.

We note that the link from your website to Dr. Mazlen’s CFS Radio Program has been discontinued since March 10, 2000, however, the link to the patient testimonials is currently active.

Your response should be directed to the undersigned by fax at (301) 594-6771, or at the Food and Drug Administration, Division of Drug Marketing, Advertising and Communications, HFD-42, 17B-20, 5600 Fishers Lane, Rockville, MD 20857. DDMAC reminds Hemispherx that only written communications are considered official. 

In all future correspondence regarding this particular matter, please refer to MACMIS ID #8800.

Sincerely,

Ele-Ibarra-Pratt, RN., M.P.H.
Regulatory Review Officer 
Division of Drug Marketing, 
   Advertising, and Communications