The FDA denied the drug application for Ampligen, asking the manufacturer, Hemispherx, to complete new studies

The FDA denied the drug application for Ampligen, asking the manufacturer, Hemispherx, to complete new studies

Hemispherx released a statement on Monday indicating the FDA had denied their application of Ampligen to treat Chronic Fatigue Syndrome (ME/CFS) because of a lack of ‘substantial’ proof of efficacy and (rather ominously) because they did not have enough data to assess safety concerns.

The FDA’s denial of the application has not been made public and may never be made public (Hemispherx’s decision) but  Hemispherx’s report and its actions, including a formal appeal of the decision, suggest the FDA’s requirements may be beyond their capabilities.  Those requirements include having Hemispherx conduct ‘at least’ one clinical trial, complete various nonclinical studies and perform several data analyses.  Hemispherx was not able to comply with similar FDA requirements in 2009 and it’s not clear why they would be able to comply now.

The FDA had other choices; they could have conditionally approved the drug with tight restrictions.  They could have required a smaller trial within Hemispherx’s budget and, after that was completed,  conditionally approved the drug (with more studies to come). The problem for Ampligen, after all, appears to be largely financial; Hemispherx doesn’t appear to have the money for the large studies the FDA wants and with their stock in the dumps, and investor lawsuits underway it’s hard to imagine they’ll be able to get it now.

Unless something changes the fight to get Ampligen approved appears to be over – for good.

The goal on the patient end was simply to find a way to get the money to do the studies this drug needs to get  FDA approval but  FDA doesn’t appear to be interested in finding ways to make this situation work…

They sure talk a good game, though.

Out of Touch Agency…

Things seemed far different a couple of months ago when, for once, things seemed to be trending in this disorder’s direction. After a 2012 law (FDASIA) specifically directed the agency to put a premium on finding ways to get drugs to people with serious disorders with few treatment options, it seemed the times were made to order for Ampligen and ME/CFS.

Citing what they called an ‘incredible’  response from the chronic fatigue syndrome community (over 750 testimonials) the FDA rep said they got it….this community is in dire need of treatment options and they were working for them.

The FDA’s public statements that they considered ME/CFS to be a serious and life-threatening condition also seemed to be setting the community up for a win.  Woodcock could have been speaking directly about ME/CFS  and Ampligen when she said

A promising but not yet fully evaluated treatment may sometimes represent the best choice for individuals with serious or life-threatening diseases who lack a satisfactory therapy.

Let’s see……Ampligen is definitely promising…..according to the FDA it’s not fully evaluated….. chronic fatigue syndrome is a serious disorder…it doesn’t have satisfactory therapies…check, check, check, check…..but no, Dr. Woodcock must have been referring to other disorders…

Indeed, as Dr. Woodcock indicated, the FDA has shown the ability to bend many times in the past. Citing a lack of other treatment options, it had recently gone so far as to approve a drug for lupus that didn’t even meet its final endpoints.

The FDA wants much more safety data for Ampligen but it does not need huge patient databases to make a decision. In a 2011 Congressional Hearing, Dr.  Woodcock noted the FDA  approved a drug for a disorder (N-acetyglutamate synthase deficiency) that affects less than 10 patients in the US on the basis of a  ‘case series of 23 patients.

The FDA relies on doctors’ opinions to assist it in making its decisions but not with ME/CFS. At the FDA-sponsored Chronic Fatigue Syndrome  Advocacy meeting Dr. Kweder stated that doctors’ statements are given weight in cases where other data is not available yet the FDA panel was advised not to strongly consider doctors’ reports at the FDA Advisory hearing.

The FDA also routinely requires post-marketing studies to address safety concerns not met by study data – but not with ME/CFS. In 2011 Dr. Woodcock noted that in the past 4 years the FDA had required drug companies to carry out approximately 375 ‘post-marketing studies’ which addressed safety questions that had not been adequately addressed prior to approval yet that was not an option for Ampligen even though its own Advisory Committee voted 8-5 that the drug was safe enough for marketing.

If the drug is safe enough and patients are made aware of questions regarding efficacy, then surely they’re capable of determining whether they want to try the drug.  Should they not be able to make that decision?

What is the greater evil? Allowing very ill patients the opportunity to try a drug that needs more study but that doctors vouch for and studies suggest is safe or denying everyone the opportunity to even try the drug for fear that something bad is going to crop up?

The Ampligen application had problems; the age of the studies, the shifts some studies took in midstream, the questions about data, and the FDA’s harsh response suggested that this drug application had more problems than usual.  But it also had its successes; it did meet its endpoints and the drug appeared to be safe and physicians and patients strongly vouched for it.

Magnifying everything was the likelihood that the request for more studies doesn’t just put a promising treatment off into the future; it very likely kills it forever.

Bob Miller knows what that means….

“It means I’ll slide back and it’s not just me. Where we’re going is back to our beds and being chained to our houses.”

For everyone chained to their houses or their wheelchairs or whatever, it means an opportunity you’ll never have…

 Agency With Its Head Stuck in the Sand

Federal-government-ignores-The FDA recognizes that ‘orphan’ disorders; ie disorders that affect small numbers of patients – don’t get the funds necessary to produce large studies so it relaxes its requirements for them. The goal, after all, is to help people get the drugs they need…not to follow some standardized protocol for testing.

CFS is not an orphan illness – too many people have it  – but it shares some important features. The fact that it has, except for Hemispherx been orphaned by drug companies leaves  ME/CFS and patients with rare diseases dwelling in a   treatment ‘ghetto’ that’s devoid of FDA-approved drugs. The only differences between the two are that there are a lot more ill ME/CFS patient and that people with rare diseases get help and people with ME/CFS get penalized for having a disorder that’s different.

If the FDA’s role is to truly to bring safe and effective drugs to ill patients it must take into account factors that impede that.  That includes recognizing the difficulties disorders like ME/CFS have in attracting major drug company support and the difficulties small drug companies like Hemispherx have in participating in an unbelievably expensive drug approval process.

After the FDA Advisory Meeting, I told the same FDA rep who’d announced that the FDA had ‘gotten it’ regarding chronic fatigue syndrome that she’d just participated in forever killing  Ampligen for ME/CFS patients. I asked her if Hemispherx had taken 20 years to get to this point and had been unable to produce the study the FDA wanted in 2009, why did she think it would be able to produce another study in 2012.

This was a  difficult question for her for at least three reasons; she’d publicly recognized how much the community needed new options, the dramatic patient testimony still lingered and many of the panel members agreed the drug did appear to be effective for at least some patients. Had she just supported removing the one drug possibility from a community that had none?

She basically rejected the question stating that economic feasibility was not their concern and they couldn’t factor that into their calculations.  But why not? Economic feasibility is factored into the equation for people with orphan illnesses.   In fact, direct federal support is sometimes given to small orphan disorders to produce drugs.

But chronic fatigue syndrome, ironically,  is too big to meet orphan disorder status and so the FDA  expects products for it to jump through the same hoops that drugs for cancer or heart disease do.

But chronic fatigue syndrome is not cancer or diabetes and or asthma; instead of several hundred million dollars a year in research, it gets six. It’s a relatively young disorder to the research community, it’s probably larded with subsets and it’s going to be a while before it’s ‘clean enough’ for drug companies or large numbers of researchers to be interested in it. It’s probably not going to get the big studies the FDA wants.

Until disorders like ME/CFS get acceptable levels of support they’re going to need some help, and until they get it, the patients are going to feel the pain that the lack of flexibility, understanding, and ultimately commitment at the federal level produces.

It appeared for a while that the FDA was the one federal agency that put the patients first; their mandate after all is to get drugs out to ill people, but they didn’t put patients’ needs first in this case; in the end they, like the NIH and the CDC wanted ME/CFS to be cancer or heart disease and when it wasn’t they turned it aside.

In the meantime, the patients bear the weight of having an illness that is different.

This disease really needs a champion -someone in power in the federal arena who is courageous enough and committed enough to take some chances –  and we just don’t have that in the FDA or the NIH or the CDC.

Hemispherx To Appeal Verdict

Hemispherx formally appeals the FDA's verdict

Hemispherx formally appeals the FDA’s verdict

Hemispherx is not going quietly. In their press release, Hemispherx hit the FDA hard, essentially accusing them (in polite terms) of ignoring a Congressional mandate (FDASIA Act) to bring stakeholders (sponsors, patients, researchers, and clinicians) together to ‘overcome challenges and find solutions.

In the end, Hemispherx believes the FDA simply made the wrong decision and they think they have the data to prove it.  Several Hemispherx reps reported great frustration at the lack of opportunity they felt they were given to respond to issues the FDA raised at the FDA Advisory Meeting.  Hemispherx’s request for an ‘end of review conference’ prior to their submitting a formal appeal of the FDA’s decision should remedy that.

The conference is designed to address the issues the FDA raised in verdict (‘Complete Response Letter’) as well as highlight clinical evidence from physicians and patients and other data indicating Ampligen’s safety and efficacy. Not surprisingly, they cited   Dr. Klimas recently published letter of support.

Hemispherx is taking the risky option of further angering the FDA with their appeal.  If they had a better option they would probably take it but with their  stock plummeting and expensive new studies in front of them   they may have no better options.




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