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

by CORT on MARCH 18, 2012

via Phoenix Rising

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. This study constitutes Hemispherx’s response to the problems the FDA cited in its refusal to approve Ampligen for CFS in Dec 2009.

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 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 but Hemispherx has persevered.

It wasn’t easy…..Hemispherx had to apply for two extensions on its drug application but 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.

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 – In this latest study Hemispherx complied with several of the FDA’s requests. It provided proof of efficacy in a larger study and provided more data on safety issues. The FDA, however, rejected Hemispherx’s claims of Ampligens efficacy in two studies that had similar findings. A third study should help but while Hemispherx did fund a larger study (@ 200 people) it wasn’t able to met the FDA’s requests for a 300 person study or to examine the effects of multiple dose ranges or do rodent studies.

Will this be enough for the FDA? Disorders which have no drugs available tend to get a break with them but Ampligen’s road with the FDAhas been a long one and only time will tell.

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.


Ampligen Study Take II: A Correction

by CORT on MARCH 18, 2012

The recent blog [above] on Hemispherx’s Ampligen study has been amended to take account of the fact that the study involved an analysis of data from a 1998-2004 study. The blog in its original state suggested that this was a new study done in response to the FDA’s 2009 concerns. That was not true. Hemispherx may have done a re-analysis of old data in an attempt to comply with some of the FDA’s concerns but it did not, at least in this paper, embark on a new study with new patients. My apologies for any misconceptions.

 


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