Ampligen Study Sparks Hopes for FDA Approval of First Drug for CFS

March 18, 2012

Posted by Cort Johnson


Short-take: Hemispherx provides added proof of Ampligens efficacy in ME/CFS and allays safety fears but is it enough?

Hemispherx has published a major study on the effects of Ampligen (Rintatolimod) on CFS. Ampligen has been under the gun since the FDA’s refusal to approve the drug in 2009, pending more study.

A Big Blow – In what journalist (and Hemispherx critic) Adam Feuerstein called a ‘staggering blow’, in Dec. 2009, the FDA told Hemipherx that it could not approve Ampligen’s use in ME/CFS until the following issues have been settled. Hemispherx needed to:

  • Show credible evidence of Ampligen’s efficacy using expanded studies that are at least six months long
  • Show that Ampligen is safe; ie that it does not cause autoimmune disorders or heart problems (prolonged qt intervals)
  • Produce studies in which patients are on more than one dose regimen
  • Produce studies in which at least 300 patients are on doses intended for the market
  • Follow the FDA’s ‘recommendation’ that rodent studies be done to examine carcinogenicity
  • Provide additional data on quality control issues
  • Fix Inspection issues at one of Ampligen’s facilities

The FDA asked a lot for a small company when it asked for an expensive 300 person study and Hemipherx stock prices plunged 43% on the news. A strong skeptic, journalist Adam Feuerstein noted that Hemispherx has unsuccessfully attempted to prove the drug works in a ‘dizzying’ array of diseases (hepatitis B and C, smallpox, HIV, ebola, avian flu , swine flu- HINI) and predicted the drug would never be approved. (Shortly after the XMRV Science paper, in an ill-fated move, Hemipherx embarked on studies attempting to prove Ampligen efficacy in treating XMRV infected patients.) Feuerstein suggested the company might not be able to financially meet the FDA’s demands.

Now in a study featuring some of the most well-known CFS providers (Dr. Peterson, Dr. Bateman, Dr. Lapp) they’ve provided the FDA with their best response to its concerns. This placebo- controlled, double-blinded, crossover study may be a make or break moment for Ampligen. The catch? This is not new data – this data comes from a 8 year old NIH study that was finished long before the FDA review in 2009.

Tough Test – Hemispherx had a tough test. The ME/CFS patients taking Ampligen had to become physically stronger; specifically they had to walk significantly longer on a cardiopulmonary exercise test than those who were taking saline solution. (Hemispherx originally used Karnovsky (functional self-assessments) as the end-point for their studies but Karnovsky score increases (50-55), while helpful, were not particularly significant).

Hemispherx looked at past exercise tolerance studies to determine how much improvement the FDA has needed to approve drugs that purport to improve exercise tolerance and found that the magic number was “6.5″. They felt if they could show that people on Ampligen walked 6.5% longer than the people on the saline solution Ampligen should – according to the past history of FDA decisions – have a good chance of getting approved.

A Sick Group – with Karnovsky scores from 40-60 this group was pretty ill. The median Karnovsky score for the group was 50 which translates out to ” requires considerable assistance for daily care”. (Hemispherx called the study members ‘severely debilitated’). Most were middle-aged women (67-77%) (average age 43 years) who had been ill for about 9 years. Given the quality of the doctors participating in the study there was no question about whether they had CFS or not.

This was a big study over 200 people starting the study and with 194 patients completing it.

The Test – the participants were asked to walk until they could walk no more on a treadmill which tilted up and got harder to walk on the longer they walked.

The Results

  • Exercise Tolerance – At the end of 40 weeks, the patients on Ampligen were able to stay on the treadmill about 108 seconds longer while the patients not on Ampligen were able to stay on the treadmill about 27 seconds longer. This translated to an 16.6% increase in exercise tolerance – far surpassing their goal of at least 6.5%. In fact, according to the study, the 16.6% increase makes Ampligen the best exercise intolerance reducer yet tested by the FDA. (The next best result was posted by Tracleer for pulmonary hypertension (10.6%) and then Remodulin (8.0%).)
  • Safety Issues -Few serious side effects were seen in this study and with earlier data suggesting that Ampligen may, in fact, have positive effects on the heart, hopefully the FDA’s fears have been allayed.
  • Decrease In Other Drug Use – Hemispherx was eager to show that taking Ampligen enabled patients to reduce their use of other drugs. Interestingly, most patients in both the saline and Ampligen arms of the study reduced their medication usage but patients on Ampligen reduced their drug use more than those on the placebo. (Some of the drugs that were reduced when Ampligen was being used may have contributed to the heart issues the FDA was concerned about.)
  • Well-being Scores – Ampligen treated patients increased their Karnovsky scores from a median of 50-55 (requires considerable assistance for daily living to requires less assistance for daily living), their vitality score doubled and their activity score went up somewhat (but was ‘significant’). Interestingly their SF-36 scores, a common measure in CFS studies to measure perceptions of general health, did not budge at all.

Check Them Off – Ampligen increased exercise tolerance, reduced medication usage, improved most well-being scores and was safe.

Conclusion -Hemispherx has taken two extensions, the latest coming earlier this year, from the FDA for its response to the FDA concerns. This study looked to be that response but it appears that this study simply analyzes data taken from a 2004 study….Hemispherx appears to hope that this analysis of the old study results will help them with the FDA.

Will it be enough? Disorders for which no drugs are available can get a break with the FDA but Hemispherx has not yet responded to several of  the FDA’s concerns; it did not do a 300 person study, did not assess responses to different doses and did not do a rodent study.

Is Ampligen the cure for ME/CFS? Not according to this study but it does appear to have passed several FDA criteria for approval. While the results weren’t stunning we know that some people do very well on Ampligen and if the FDA approves this drug determining who it works for will be important and could ultimately help to subset this disorder. Hemispherx believes the work its doing with a biotech firm called Chronix (see below) will allow it to pinpoint individuals who will benefit from the drug.

Dig Deeper

Other Hemispherx News

In March 2011 Hemispherx announced that it and Chronix had joined forces to produce a diagnostic test for ME/CFS using advanced DNA sequencing techniques. Howard Urnovitz, Chronix CEO suggested a revolution in understanding ME/CFS was in store stating

“”We capture what is happening to the DNA very early in and throughout the disease process, in real time, and patient by patient,” Howard Urnovitz, CEO and CSO of Chronix Biomedical, said in a statement today. “That’s how our approach differs from other tests that focus on static genomic data or protein biomarkers.”

The companies applied for a patent for a blood test for ME/CFS and stated their new technology would also reap dividends in determining which types of CFS patients responded to Ampligen.

 

22 comments

{ 21 comments… read them below or add one }

leela March 18, 2012 at 2:02 pm

One small point…don’t many PWCs do better on simple saline due to blood volume issues?

And yes, the reported gains hardly seem worth the cost and effort involved.

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Cort March 18, 2012 at 8:17 pm

Yes they do but the gains by the placebo taking patients were not that spectacular which suggested to me that they were probably just the results of the placebo effect.

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anita March 22, 2012 at 4:57 am

The gain is so huge that it is worth any effort involved. There is nothing else that is available that works as well. Thank you, Cort, for this very good article on Ampligen!

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Cort March 22, 2012 at 2:58 pm

Thanks again Ann…let’s hope Ampligen finally gets over the hump and gets approved.

Tom Kindlon March 18, 2012 at 5:06 pm

From the paper: “This study was initiated on 12/17/98, and ended following full enrollment on 8/16/04 when the last patient completed.” That’s a long time ago. I’m far from an expert on the FDA but could it not be the case that they have already ruled on this data?

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Cort March 18, 2012 at 7:46 pm

Agreed Tom…that was so strange that I just bypassed it. I’m just bamboozled by this… Why would Hemispherx report on a study that was 8 years old? I couldn’t conceive that they would do this so I assumed that they weren’t but it looks like they were. Several years ago a journalist named Feuerstein called Hemispherx to task for providing different results for the same study several times and predicted the drug would never get approved.

I’ve redone sections of the article to reflect the actual dates of the study. I assume that Hemispherx is hoping that re-analyzing the data will be sufficient to allay the FDA’s concerns but that seems like a long shot to me.

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Heather Reddy March 18, 2012 at 7:57 pm

if this drug is approved in our lifetimes, it will be the end of so much suffering. my heart is in my chest reading this!

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Donna Kalichstein-Lehrman March 18, 2012 at 8:03 pm

Great there may be a new drug…but I wonder how long the side effect list is???

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Phoenix Rising March 18, 2012 at 8:20 pm

The side effects are there but they are presented as fairly minor…Of course you never know until you try it.

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Phoenix Rising March 18, 2012 at 8:20 pm

I’m hoping not only for patients but for the state of the science. I think a drug approval for Ampligen would spark more interest and research into the immune side of CFS…

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Donna Kalichstein-Lehrman March 18, 2012 at 9:11 pm

I usually wait till a drug is on the market for a while…let’s hope this gets approved and it works well

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Joni Lohbeck Lewandowski March 18, 2012 at 9:43 pm

I’m so ready!!!!!!!

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Laura Dickinson March 18, 2012 at 9:44 pm

This is a very expensive drug at about $12,000 for a six month course. It also has to be administered inter-venously twice a week. I am completing testing to join the study right now and this makes me wonder if it is worth it for the 16% more exercise tolerance and no perceived health improvement?

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Nancy Rouch March 18, 2012 at 10:01 pm

I hope this study gets approved!

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Phoenix Rising March 18, 2012 at 11:05 pm

Remember these are averages….I know of some people for whom Ampligen was a life-changer and others for whom it just didn’t work or didn’t work very well. If you’re in the ‘it made a huge difference for me’ group I imagine it would be worth it…if you were in the other group I imagine it wouldn’t be. If you get into the study I hope you’re in the first group. It sounds like Hemispherx thinks they’re going to be able to use genetic or gene expression testing at some point to target people for whom the drug works. Whatever you do – good luck!

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Maisie, Scotland March 19, 2012 at 6:57 am

Any word on when a pill form of Ampligen might be available?
Also, does Ampligen work in much the same way as Low Dose Naltrexone and have the same efficacy?

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Alex March 19, 2012 at 12:48 pm

Cort, I don’t know where your reasoning is coming from here. What is the basis for your conclusion that *this* is Hemispherx’s attempt to respond to the FDA’s concerns outlined in the CRL?

This isn’t a re-analysis of the data from the phase-III study– it is the first time the data from that study have ever been published in a scientific journal! This is what was submitted to the FDA in the first place. They are now making it public so that it can be evaluated by the scientific community.

It is not completely clear how the company plans to respond to the FDA’s concerns, but they have hinted that they are betting that the Chronix collaboration is going to identify a biomarker for Ampligen responders. Then, they could do a smaller study on just this subset, prove that Ampligen is *very* effective for this subset in a smaller follow-up study, and do a bit of additional work to assess safety concerns.

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Cort March 20, 2012 at 3:52 pm

Agreed Alex – I submitted a follow up correction. I missed the date of the study (I don’t usually check that out – but should have in this case).

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Alex March 19, 2012 at 12:55 pm

Also, the FDA’s reasoning on safety issues is just deplorable here. The CFIDS Association and other advocacy groups should be up in arms over this.

There is no credible evidence that Ampligen causes prolonged QT intervals or autoimmune disease. Even if there were, it should not be a basis for refusing to approve the drug. Their underlying assumption is that a CFS drug must be almost perfectly safe.

CFS is as crippling as Multiple Sclerosis, Rheumatoid Arthritis, Lupus, and COPD. A great many drugs have been approved for these other diseases that carry a small risk of very serious side effects because they are SERIOUS DISEASES and doctors have a right to make a risk/benefit analysis. WHY isn’t OUR disease SERIOUS to these people!?!?!?

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Ginny April 28, 2012 at 1:50 pm

When I was in the early studies for Ampligen and CFS It didn’t help me. I still suffer with CFS … the cost of Amjpligen is also out of this world…. one on disablility can not afford it….

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Cort April 28, 2012 at 2:40 pm

Thanks Ginny, unfortunately not everybody responds to Ampligen…and it is very expensive….Two thoughts – even if only 30% of people with CFS respond – that’s still an enormous group of people and two – if Ampligen could be given accelerated approval by the FDA that would help Hemispherx fund studies with the result that the price would come down substantially. Good luck with everything!

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