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.
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?
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.
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.
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…….
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 ???
Thanks,
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.
HIROAKI MITSUYA, M.D.
KENT WEINHOLD
ROBERT YARCHOAN, M.D.
DANI BOLOGNESI
SAMUEL BRODER, M.D.
Bethesda, Md., Sept. 20, 1989
—
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.
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.
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…?
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
encephalitis….”
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:
http://www.amazon.com/Americas-Biggest-Cover-Up-Everyone-Syndrome/dp/0962414239/\
ref=sr_1_1?ie=UTF8&qid=1359080456&sr=8-1&keywords=America%27s+Biggest+Cover-Up%3A+50+More+Things+Everyone+Should+Know+About+The+Chronic+Fatigue+Syndrome+Epidemic+And+Its+Link+To+AIDS
The entire book is transcribed here: http://www.fms-help.com/aids.htm
My life with NON HIV AIDS has been published 11 times on 4 continents: http://ukprogressive.co.uk/the-aids-like-disease-seldom-mentioned/article20891.html
AZT is rat poison. [i]”death by prescription”[/i]
http://www.virusmyth.com/aids/hiv/hkslahprotease.htm
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]
http://en.wikipedia.org/wiki/Black_box_warning
They also won’t approve Ampligen because it works! It would work in AIDS patients too.