Ampligen is Not AZT

In recent weeks, some ME/CFS advocates have been calling for NIH to conduct a clinical trial of Ampligen based on the reasoning that NIH conducted trials of AZT during the early years of the AIDS crisis. Unfortunately, this analogy does not hold up to scrutiny and should be abandoned as an argument in favor of Ampligen.

AZT was invented in 1964 by researcher Jerome Horwitz under an NIH grant to the Michigan Cancer Foundation. The compound was shelved after it failed early trials in mice. By 1984, when the hunt for an AIDS treatment was in full swing, AZT was the property of Burroughs Wellcome (now GlaxoSmithKline). Burroughs had done some research into AZT, and thought it might act upon HIV. However, Burroughs did not have the facilities needed to work with active HIV. At this same time, National Cancer Institute researcher Sam Broder and collaborators had developed a CD4+ cell line (the kind of immune cells vulnerable to HIV). Broder was begging pharmaceutical companies to send him compounds to test for effectiveness against HIV in that cell line. Burroughs sent a number of compounds to Broder for testing, including AZT.

In February 1985, Broder reported to Burroughs that AZT was very effective against HIV. NIH and Burroughs entered into a collaboration for the first Phase 1 trial of AZT in humans. Specifically, 19 AIDS patients were treated with the drug at the NIH Clinical Care Center in July 1985. Fifteen of those patients showed clinical improvement during the treatment. Although the drug had significant side effects, the phase 1 trial did establish that it was safe to give to humans (the objective of phase 1 trials). Conducting the remaining clinical trials of AZT was the responsibility of Burroughs. After a double-blind placebo controlled trial in 282 AIDS patients in 1986, the FDA approved AZT for use in 50,000 severely ill AIDS patients in March of 1987.

In contrast, Ampligen has been developed by Hemispherix Biopharma for more than 20 years, from inception through Phase 3 clinical trials. FDA has reviewed and denied approval to Ampligen twice (2009 and 2013). It strains credulity to claim that NIH should initiate an Ampligen study when the drug has been denied twice, particularly given that the FDA Advisory Committee voted 9 to 4 that there was not substantial evidence of efficacy. The situation is further complicated by the rumors that Hemispherix is in serious financial trouble (although its CEO was just given a $250,000 bonus). If NIH were to intervene now, that might look like another government bailout of a failing company and that hardly seems like a precedent NIH would want to set.

Coincidentally, Dr. Anthony Fauci (Director of the National Institute for Allergy and Infectious Diseases) described NIH’s involvement in drug development in an interview last week (the interview did not mention ME/CFS). Fauci said that NIH is usually involved in funding basic research and industry funds drug development and testing. Sometimes, industry conducts basic research and sometimes, NIH participates in early drug development as it did for AZT. But while each side might depart from its normal participation to a degree, he did not cite any examples where NIH first stepped in at the very end of a drug development process.

Is there any path forward for Ampligen at NIH? The CFIDS Association recently urged Hemispherix to initiate applications to NIH through the National Center for Accelerating Translational Science and the December 2012 RFA from the NIH Clinical Care Center. Whether Hemispherix will initiate such applications, and whether NIH will fund them, remains to be seen.

In the meantime, we look foolish (at best) if we claim that the Ampligen situation is just like AZT and that therefore NIH should conduct a clinical trial. The historical parallels just are not there.

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10 Responses to Ampligen is Not AZT

  1. Kati D says:

    hi Jennie, thanks for these explannations. My question to you (I know this is the million $ question) is how do we get out of the hole we’re in? how do we get attention and action from our governments, and this applies not only to the US governments but all around the world.

    I’d say this in not necessarily bout Ampligen, but it’s about us patients being taken seriously, we’ve been sick for decades and we are treated as second class citizens. How to get out of that hole? What will it take?

    • Jennie Spotila says:

      As you say, Kati, that’s the million dollar question. I think we could start by advocating for research and treatments more broadly relying on all the evidence of the seriousness of this disease. We should look for ways to amplify that message.

  2. Kati D says:

    A second comment loosely related to your post. Dr Peterson said in his recent address at Nova University that Ampligen is available in Canada. Well, maybe and no. There are no physicians willing to give it here.

  3. Angel Mac says:

    Well, the NIH/NCI has already had 30yrs to research and come up with a different drug which to date they have not. If HEB is not going to go any further, why doesn’t the NIH/NCI conduct the trial they want since Ampligen is the FIRST thing that has helped many people in all of these years… AZT was not the last drug and I’m sure Ampligen won’t be either,
    but we need the NIH/NCI to get off their butts and DO Something !!
    30yrs and 17 million people is too many for too long for them to
    play dumb and Do NOTHING Positive to Help !
    The parallel is that those were the 1st drugs that helped !
    Let the people have them…….

  4. Robert Miller says:

    These Government scientist say different, HIROAKI MITSUYA, M.D. KENT WEINHOLD, ROBERT YARCHOAN, M.D. DANI BOLOGNESI and SAMUEL BRODER, M.D. in this letter to the Editor.

    They state the Government did a much larger portion of the work using Government funding to develop and get approval for AZT. Burroughs made the money with little cash or time invested. Hemispherx has done the work for 20 years, the FDA Advisory Committee voted 8 to 5 in favor that Ampligen is safe to approve for the indication of CFS. For NIH to assist now for the benefit of patients is the right thing to do. To Collaborate with the sponsor is not new. HHS has not been invested in this illness for over 20 years, it’s time for them to step up. No one is saying that the Ampligen situation is just like the AZT situation, but they are similar. ME/CFS experts using Ampligen can measure patients immune systems to prove the drug works with minimal side effects. Call Klimas, Peterson or Lapp re: improved: NKC function, T-Cells, Cytokines and more. As far as the CEO taking a bonus, does that really have anything to do with treating patients with a drug that works. How much did the CEO of Burroughs get the year before they marketed AZT ???

    Robert Miller

    New York Times, September 28, 1989

    Credit Government Scientists With Developing Anti-AIDS Drug

    To the Editor:

    The Sept. 16 letter from T.E. Haigler Jr., president of the
    Burroughs Wellcome Company, was astonishing in both substance and
    tone. Mr. Haigler asserts that azidothymidine, or AZT, was
    essentially discovered and developed entirely by Burroughs
    Wellcome with no substantive role from Government scientists and
    Government-supported research. This will be a surprise to the
    many men and women who have devoted their lives to working for
    the viral cancer program and developmental therapeutics program
    of the National Institutes of Health over the last 25 years.

    We (associated with the National Cancer Institute and Duke
    University) make this statement as co-authors of the first
    publications describing AZT as a drug for treatment of acquired
    immune deficiency syndrome (Mitsuya, et al., Proceedings of the
    National Academy of Sciences, 1985, and Yarchoan, et al., The
    Lancet, 1986). There are few drugs now approved in this country
    that owe more to Government-sponsored research. In the interest
    of brevity, perhaps this point can be summarized most efficiently
    by stating what Mr. Haigler’s company did not do.

    – The company did not perform the first synthesis of AZT. This
    was done by Dr. Jerome Horowitz at the Michigan Cancer
    Foundation in 1964, using a Government grant.

    – The company did not conceive or provide the first
    demonstration of an effect against animal retroviruses. This
    was done by Wolfram Ostertag at the Max Planck Institute in
    1974, using a mouse retrovirus in a test tube. Mr. Haigler’s
    implication that his staff discovered” the antiretroviral
    potential of AZT in 1984 is noteworthy. What he did not say
    was that his staff repeated the Ostertag mouse experiments.
    You cannot discover” something published by someone else 10
    years earlier.

    – The company specifically did not develop or provide the first
    application of the technology for determining whether a drug
    like AZT can suppress live AIDS virus in human cells, nor did
    it develop the technology to determine at what concentration
    such an effect might be achieved in humans. Moreover, it was
    not first to administer AZT to a human being with AIDS, nor
    did it perform the first clinical pharmacology studies in
    patients. It also did not perform the immunological and
    virological studies necessary to infer that the drug might
    work, and was therefore worth pursuing in further studies.

    All of these were accomplished by the staff of the National
    Cancer Institute working with staff at Duke University. These
    scientists did not work for the Burroughs Wellcome Company. They
    were doing investigator-initiated research, which required
    resources and reprogramming from other important projects, in
    response to a public health emergency.

    Indeed, one of the key obstacles to the development of AZT was
    that Burroughs Wellcome did not work with live AIDS virus nor
    wish to receive samples from AIDS patients.

    In a number of specific ways, Government scientists made it
    possible to take a drug in the public domain with no medical use
    and make it a practical reality as a new therapy for AIDS. It is
    unlikely that any drug company could have found a better partner
    than the Government in developing a new product. We believe that
    the development of this drug in a record two years, start to
    finish, would have been impossible without the substantive
    commitment of Government scientists and Government technology. It
    does not serve anyone’s interests to nullify the importance of
    Government-sponsored research in solving problems of American
    public health.

    Bethesda, Md., Sept. 20, 1989

    • Jennie Spotila says:

      The issue is not who deserves the credit for AZT. Litigation in the late 1980s and early 90s ended in favor of Burroughs Wellcome. The most significant part of the letter you quote is the statement that AZT was in the public domain. Ampligen is not in the public domain. It is an intellectual property asset of a for-profit company.

      NIH was the only entity able to do the early work on AZT and HIV because they had the cell line and ability to work with the virus. After the phase 1 trial, NIH stepped back and Burroughs Wellcome took the lead. The suggestion that NIH step in to Ampligen now is not analogous because it is at the end, not the beginning, of the development cycle. That doesn’t mean NIH can’t be involved as a partner. The CFIDS Association pointed out two ways that Hemispherix could initiate requests for NIH support.

      I am also not saying that the government should not work with Hemispherix. I would like to see a larger double blind placebo trial of Ampligen, or even a randomized withdrawal study as was suggested at the advisory committee meeting. All I’m saying is that the AZT analogy doesn’t work and we should use a better foundation for the argument. Anyone in our audience familiar with the history of AZT will spot the weakness in the analogy and potentially dismiss the entire argument as a result.

  5. Kati D says:

    What strategy will work I don’t know. What I know is that my can. government seems very proud of the 5 cents funding per patient with ME per year, and that maybe we will get a 5000$ worth undergraduate grant this year. With no government funded research, it’s as if we didn’t exist. Advocating for health care while we are sick as dogs is a very hard thing to do.

    The HIV/AIDS analogy sounds fair to me, because look at them now- 30 years down the road, it’s the most funded disease year after year after year. There are dozens of drugs now. Less mortality. Patients are functional and useful to society.

    I personally think the hunger strike strategy was a very good one. Now that Robert has secured a big meeting, it’s time to get our requests heard loud and clear and not back down. I also think the time factor is important. Not in 6 months, not in 2 years, now! Perhaps hiring a lobbyist (I’d pay into that) could be a good thing.

  6. Emma says:

    Thanks for this post, Jennie. I agree that we need to use only foolproof arguments in order to get our message across. Your analyses are always helpful.

    I also think Kati D’s question is really important – what can we do? – and I want to thank Robert and Courtney Miller and many others for their untiring advocacy resulting in the attention of some high level officials. We need to do everything we can to move things forward from here. Let’s keep working as a community, maybe we’re on our way…?

  7. cfsboston says:

    European Vacation – Clark Griswold: [Clark is driving around Lambeth Bridge
    Roundabout in London, England, unable to turn to the left]

    “Hey look kids, there’s Big Ben, and there’s Parliament… again.”

    As-if proof is really necessary that CFSers’ are being herded around in
    decade-long circles, this is Chapter 46 right from a book published in 1993!

    Chapter 46:

    “An Experimental Drug That Appears Promising For CFS And AIDS Is Being Evaluated
    By The FDA

    In February 1993, the Food and Drug Administration’s Anti-Viral Drug Advisory
    Committee met to consider the merits of an experimental drug, Ampligen, that
    appears to have promise for treating CFS (and, in earlier trials, AIDS). So far,
    no drug has been approved for the treatment of CFS by the FDA.

    Ampligen appears to correct a defect in a very important natural anti-viral
    pathway. When this pathway isn’t working properly, viruses aren’t attacked by
    the body’s natural defenses. In CFS patients, as in AIDS patients, this
    anti-viral pathway is defective; furthermore, Ampligen appears to correct the
    defect in both sets of patients.

    At the February meeting at the FDA, Kim Kenney of the CFIDS Association of
    America (in Charlotte, NC), told the FDA that approving a drug to treat CFS is
    extremely important to patients, many of whom are desperate to get better. She
    told the FDA that “the reactions of our constituents range from impatience to
    desperation, depending on the severity of their condition. Impatient to get back
    to work, to enjoy their families again. And for some, desperation to reverse the
    severely debilitating effects of CFIDS, including dementia, unrelenting muscle
    and joint pain, severe encephalitis, not to mention the problems that accompany
    a severely impaired immune system.”

    Dr. Daniel Peterson, one of the two physicians who identified the original
    outbreak of CFS in Incline Village, Nevada, in 1984, told the FDA committee that
    “a significant number” of his patients who fell ill in 1984 “never recovered.”
    Dr. Peterson also said that, over the last eight years, 20 percent of the
    patients he’d examined had become completely disabled. Dr. Peterson also
    cautioned that the CDC’s “crude incidence” of four per 100,000 “most certainly
    vastly underestimates the true incidence of the disease.”

    Dr. Peterson told the FDA that, although Ampligen “appears to have great
    potential in this disease process, it has been bogged down in a corporate and
    bureaucratic quagmire, and yet the disability and anguish of the patients and
    treating physicians remains unaddressed.”

    Jerry Crum, the CFIDS Association’s co-chair of its Public Policy Advisory
    Committee, also spoke at the February meeting with the FDA. Mr. Crum described
    his illness, which began in 1985, for the committee:

    “What I remember during three years of progressive deterioration were seizures
    on an average of two to three per week and becoming severely demented. My
    short-term memory was seriously impaired. When I went for walks in my
    neighborhood, I couldn’t find my way home. My IQ dropped from 130 to 85. I will
    never, ever forget what it feels like to have an IQ of 85. I was not “stupid.”
    What I had was an indefinite sense of the world around me….If I concentrated
    very hard, I could follow conversations….I slept 14 or more hours per day and
    nothing alleviated the ever-present muscle pain I suffered from. I was bleeding
    from my colon. A lumbar puncture performed by Dr. Peterson confirmed severe

    Ampligen, however, allowed Mr. Crum to live a more normal life. His seizures
    became infrequent, his IQ increased almost to its pre-illness level, and he
    became capable of performing his job, which involved complex mathematics, again.
    “The muscle aches diminished, and I required only ten hours of sleep per night
    with a nap during the day,” Mr. Crum told the FDA. He credits Ampligen with
    allowing him to “regain a measure of quality to my life, which I thought I would
    never experience again.”

    Perhaps most compellingly, however, Mr. Crum described for the FDA what happened
    to him when he stopped taking Ampligen because, as he said, “Receiving I.V.
    infusions three times per week is not pleasant.” But, within six weeks of
    discontinuing Ampligen therapy, he once again began having seizures and his IQ
    again plummeted.

    “In short, I regressed to the same seriously ill condition I was in prior to receiving Ampligen,” Mr. Crum told the FDA Committee.

    Similar testimony from other patients, or their families if they were too impaired to deliver or prepare testimony themselves, was also presented to the FDA committee.

    The FDA, however, has yet to grant approval to Ampligen or any other drug to
    treat CFS. ”

    The actual book is:\

    The entire book is transcribed here:

    My life with NON HIV AIDS has been published 11 times on 4 continents:

  8. cfsboston says:

    AZT is rat poison. [i]”death by prescription”[/i]

    Black-box (skull&crossbones) [i]Paraphased: “We are required by law to inform you that you may die taking this drug, because others have died taking this drug.”[/i]

    They also won’t approve Ampligen because it works! It would work in AIDS patients too.

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