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Partner, NIH: Other Chances for Ampligen CFS Campaign?

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By Randy Osborne
Staff Writer

A late-stage change in clinical direction and the use of a trial placebo that turned out also to be a treatment in chronic fatigue syndrome (CFS) may have hobbled Hemispherx Bioscience Inc.'s regulatory efforts with Ampligen (rintatolimod), the Toll-like receptor 3 modulator that was hit with a complete response letter (CRL) earlier this month.

But Ampligen may still have a chance, said Kimberly McCleary, president and CEO of the Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Association of America.

The scenario "cries out for [Hemispherx] to take on a capable partner, whether that's the National Institutes of Health [NIH] or a company with more experience and some ability to provide the kind of financing that would be required," McCleary said.

"It's a shame that Hemispherx didn't undertake the Phase III [trial] they had planned, and is evident in their [quarterly statements] after the 2009 CRL," she said. "They outlined the cost per patient, and how they would trim down the costs from the last study they did, and then the strategy shifted to submitting a new analysis of the data" from the earlier, AMP516 trial.

Saline was used as the placebo control in the 516 study. "They made that decision back in the early 1990s, before anybody had connected the orthostatic and blood-volume problems in CFS," and before physicians had begun to use saline as a therapy for those problems, McCleary said. "This may have made it more difficult to show efficacy. What is the appropriate placebo, if saline has some active properties?"

Others trying to come up with therapies for CSF will face the same question. But there aren't any others, at least not in advanced stages, doing so, which means patients have all their chips on Ampligen, which already has helped many in trials. These include Robert Miller, 54, whose hunger strike to draw attention to the issue has entered its second week. (See BioWorld Today, Feb. 6, 2013.)

Until the end-of-review meeting with the FDA, Hemispherx will not have much to say about next steps. McCleary has contacted the firm, and has written a letter to Assistant Secretary for Health Howard Koh, with the Department of Health and Human Services, asking that the agency "intensify efforts that will stimulate the kind of basic, translational and clinical science to advance treatment options" in CFS.

Within its National Center for Accelerating Translational Sciences, the NIH has established the Therapeutics for Rare and Neglected Diseases program, "established with this sort of situation in mind, although I think it was geared toward the earlier stage of clinical research, and not waiting until you're in Phase III," McCleary said. "If you use [the HIV therapy] azidothymidine as the model, NIH did the Phase I and then Burroughs Wellcome [now GlaxoSmithKline plc] did the Phase II and Phase III. That seems to be the story that [Miller] and others are focused on – let's do that again."

But how soon could this happen? "That's the real big question," McCleary told BioWorld Today. "The NIH works on a completely different timeline than a corporation that's accountable to stockholders and has to please them by the start of the next quarter."

Insults from Inside and Out

Almost all patients are dissatisfied with the name given their disease, which minimizes the symptoms and turns a serious illness into something that sounds almost like lethargy. In 1988, when the Centers for Disease Control and Prevention (CDC) published the first definition and used the term "chronic fatigue syndrome," McCleary's group took up CFIDS "as a sort of protest, to at least add in the fact that there was some immune dysfunction" involved, she said. "At this point, the term isn't used all that frequently, although the immune system problems are coming back to the fore."

Widely used now is "ME/CFS," the first two letters standing for "myalgic encephalopathy" or "myalgic encephalomyelitis," depending on who's speaking, McCleary said. "People seem to have gotten past the construct of whether that matters, and even the federal agencies are using 'ME/CFS' at this point. We're making that transition ourselves."

Also heard is "post-viral fatigue syndrome," which points up the fact that CFS often follows an infection of some kind, she said. "I think there's pretty good agreement that there might be three parts to [disease]."

First is "a background genetic predisposition that's probably pretty broad," McCleary said. More females than males get CFS, and "some of the CDC studies have shown it's more common in blacks and Latinos, when you look at a population sample." Whites and Asians seem less affected.

"This probably won't turn out to be [like] Huntington's disease," in which a single gene is responsible, McCleary said. "With epigenetics layered on top of plain old Mendelian genetics, there's a lot of interest in using those tools" to figure out more. The second part of the illness is a weakened immune system, caused by an illness or stress, and the third is a triggering event, such as a virus, bacteria or chemical exposure. Somehow, a cascade of insult is triggered that the body is unable to fight off.

CSF patients often must put up with insults from outside, too. The term for their illness "doesn't buy you a lot of social capital," McCleary said. There's no question that the silly-sounding name automatically drives the conversation. [Other people say,] 'Oh, I think I have that, too. I'm tired by Friday afternoon myself.' This is the mindset people approach it with. There's a tremendous yearning within the patient community to feel understood and validated."