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.