San Fran Chronicle: CF patients frustrated with FDA [Ampligen]

[Firestormm]

Chronic fatigue patients frustrated with FDA

Erin Allday

Updated 10:40 pm, Friday, February 15, 2013

Read more: http://www.sfgate.com/health/article/Chronic-fatigue-patients-frustrated-with-FDA-4283890.php#ixzz2L3NDP3YV​

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Jeannette Burmeister worries that she will not have access to the experimental drug she takes for chronic fatigue syndrome. Photo: Paul Chinn, The Chronicle

Jeannette Burmeister lives in Incline Village, Nev., where, twice a week, she gets a three-hour infusion of a drug to treat chronic fatigue syndrome that she says has very nearly saved her life.

But it comes at a steep price: Burmeister's husband and her 2-year-old daughter live more than 200 miles away in Menlo Park, and she's able to see them only once a week. Because the drug she says she needs - an experimental medication called Ampligen - isn't approved by the Food and Drug Administration, the only way she can get it is through a clinical trial run by a doctor in Nevada.

And as of this month, when the FDA officially refused to approve Ampligen for treatment of chronic fatigue, she's not sure how much longer she'll be able to get the drug.

"The hope was that the FDA would approve it, and once it was approved other doctors could give it to me - doctors in the Bay Area. But that didn't happen," Burmeister, 41, said. "I'm hoping the drug will remain available, but who knows."

If it had won approval, Ampligen would have been the first drug available specifically to treat chronic fatigue syndrome. The drug bolsters the immune system and works as an antiviral against a variety of pathogens, according to the manufacturer, Hemispherx Biopharma in Philadelphia. Ampligen also is being studied as a possible treatment for drug-resistant HIV infections.
FDA's concerns

Ampligen was rejected because FDA officials weren't convinced of its efficacy or its safety, according to a letter sent to the drug manufacturer. There have been concerns about the drug's effects on the kidneys and liver.

Chronic fatigue syndrome can be a debilitating disease marked by oppressive fatigue that lasts for days, weeks or even months and doesn't go away with rest or proper sleep. Burmeister describes it as constantly living with the worst jet-lag combined with the worst hangover of her life.

Other common symptoms include mental fuzziness and poor memory, sore throat and headaches, pain in the joints and muscles, and gastrointestinal problems.

The disease was identified in the early 1980s, and more than a million people in the United States are believed to suffer from it. But it's only in the past decade that chronic fatigue syndrome has received serious recognition by federal agencies like the U.S. Centers for Disease Control and Prevention and the National Institutes of Health.

Research into it is still minimal. Scientists believe it's likely caused by a virus, but they've never found it. Because there is no drug to treat chronic fatigue syndrome, patients often are advised to seek behavioral therapy to learn to live with their condition.
Patient frustration

That's why the rejection of Ampligen was especially upsetting to so many chronic fatigue sufferers, said Dr. Jose Montoya, an infectious disease specialist who helped establish a chronic fatigue syndrome team at Stanford. Montoya said he isn't convinced of Ampligen's effectiveness, but he fully appreciates the frustration that patients, and their doctors, feel at having nothing to ease their symptoms.

"I have been very hesitant to use it, and I have never indicated it or prescribed it," Montoya said. "But it appears there is a group of patients that do benefit from Ampligen. And with that FDA decision, you are taking away access. It's a huge blow to the patients.

"On the other hand," he added, "we're another step toward bringing the disease to a center stage of government agencies. We're making them see that this is an unmet medical need and something needs to be done."

One man in Reno, who gets the drug from the same doctor who treats Burmeister, went on a hunger strike for 11 days over the FDA rejection. Robert Miller started eating again earlier this month, after the U.S. secretary of health's office promised to participate in a meeting between the FDA and patients, doctors and drug manufacturers this spring to discuss research into chronic fatigue.

Many patients said they understand why the FDA rejected the drug, which may be effective in only a subset of chronic fatigue sufferers. Ideally, said Miller, federal agencies would work with the drug manufacturer to conduct more clinical trials and figure out who would benefit from Ampligen. Such research might also help scientists understand what causes chronic fatigue syndrome and find new drugs for treatment.
Costly drug

Hemispherx may continue research on the drug and reapply for approval - a process the company has gone through once before - but patients worry that because Hemispherx is a small company, it may not have the resources to conduct more trials that will meet the FDA's approval requirements. Already, patients are required to pay roughly $20,000 a year, almost none of which is covered by insurance, for the Ampligen they take in clinical trials.

If Hemispherx abandons its research, Burmeister said, she probably won't be able to get the drug at all, and she is convinced that her chronic fatigue symptoms will return.

Before she started taking Ampligen nine months ago, she wasn't able to walk three blocks to take her daughter to the park, and just changing a diaper was taxing enough to send her back to bed.

"But five months into being on the drug, I could go shopping and do laundry and empty the dishwasher, all in one day. I could have coffee or lunch with friends. I hadn't socialized in years.

"If I can't get the drug anymore, I will relapse fairly quickly and go back to needing a wheelchair for more than a block, and spending most of my time in bed or on the couch," she said. "There's literally nothing else for me."

Erin Allday is a San Francisco Chronicle staff writer. E-mail: eallday@sfchronicle.com
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[Valentijn]

A pretty good article, aside from the horribly mangled/watered down description of PEM.

 

[Patrick*]

Don't read the comments section unless you're prepared to deal with unbelievable levels of ignorance, trolling, and prejudice. (At least, that was the case when I read through the comments Saturday. Maybe by now the bad comments have been buried.)

 

[Purple]

Chronic fatigue syndrome can be a debilitating disease marked by oppressive fatigue that lasts for days, weeks or even months and doesn't go away with rest or proper sleep. Burmeister describes it as constantly living with the worst jet-lag combined with the worst hangover of her life.

Wouldn't it be nice if it lasted only "days, weeks or even months".

 

[barbc56]

I couldn't stomach some of the comments after the second page. Trolls.

However, and this is my opinion, while I think there could be a valid argument that for the people Ampligen has helped could be prescribed off label, I think we need to identify the subset of those Ampligen helps. But it's kind of a slippery slope in that it has helped others, yet the medication has side effects and there aren't any scientific studies at this time that show it works. So to that extent I am glad the FDA didn't approve the drug.

It's a gray area and there are no easy solutions. I feel sorry for those it has helped and won't have access to the medication but personally, I wouldn't take it until the science works this our.

I think the responsibility of blame lies with Hemispherx for doing shoddy research and thinking it will be overlooked by the FDA. The FDA has been accused to doing this.

Barb

 

[Research 1st]

I couldn't stomach some of the comments after the second page. Trolls.

However, and this is my opinion, while I think there could be a valid argument that for the people Ampligen has helped could be prescribed off label, I think we need to identify the subset of those Ampligen helps. But it's kind of a slippery slope in that it has helped others, yet the medication has side effects and there aren't any scientific studies at this time that show it works. So to that extent I am glad the FDA didn't approve the drug.


Barb

You are factually incorrect.

There is published scientific data to show the benefits of Ampligen for people diagnosed with CFS.

A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod [Ampligen] in Severe Cases of Chronic Fatigue Syndrome



Abstract

Background

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a severely debilitating disease of unknown pathogenesis consisting of a variety of symptoms including severe fatigue. The objective of the study was to examine the efficacy and safety of a TLR-3 agonist, rintatolimod (Poly I: C12U), in patients with debilitating CFS/ME.

Methods and Findings

A Phase III prospective, double-blind, randomized, placebo-controlled trial comparing twice weekly IV rintatolimod versus placebo was conducted in 234 subjects with long-standing, debilitating CFS/ME at 12 sites.

The primary endpoint was the intra-patient change from baseline at Week 40 in exercise tolerance (ET). Secondary endpoints included concomitant drug usage, the Karnofsky Performance Score (KPS), Activities of Daily Living (ADL), and Vitality Score (SF 36).

Subjects receiving rintatolimod for 40 weeks improved intra-patient placebo-adjusted ET 21.3% (p = 0.047) from baseline in an intention-to-treat analysis. Correction for subjects with reduced dosing compliance increased placebo-adjusted ET improvement to 28% (p = 0.022).

The improvement observed represents approximately twice the minimum considered medically significant by regulatory agencies. The rintatolimod cohort vs. placebo also reduced dependence on drugs commonly used by patients in an attempt to alleviate the symptoms of CFS/ME (p = 0.048).

Placebo subjects crossed-over to receive rintatolimod demonstrated an intra-patient improvement in ET performance at 24 weeks of 39% (p = 0.04). Rintatolimod at 400 mg twice weekly was generally well-tolerated.

Conclusions/Significance

Rintatolimod [Ampligen] produced objective improvement in ET and a reduction in CFS/ME related concomitant medication usage as well as other secondary outcomes.


http://www.plosone.org/article/fetchArticle.action?utm_medium=feed&utm_source=feedburner&utm_campaign=Feed: plosone/PLoSONE (PLoS ONE Alerts: New Articles)&articleURI=info:doi/10.1371/journal.pone.0031334

 

[barbc56]

Depending on which data presentation you believe, the Ampligen study was either a success or a failure. By rejecting Ampligen in 2009, FDA clearly sided with the latter view.
In March, Hemispherx published the full data from the Ampligen trial in the open-access science journal PLOS One. Once again, the study results changed and got worse.In March,
Ampligen-treated patients with chronic fatigue syndrome entered the study with a mean, baseline treadmill exercise duration of 576 seconds. After 40 weeks of treatment, mean exercise duration rose to 672 seconds, or a 16.7% improvement.
The placebo patients began the study with a mean, baseline treadmill exercise duration of 588 seconds and ended at 616 seconds, or an improvement of 4.8%.
Ampligen-treated patients with chronic fatigue syndrome entered the study with a mean, baseline treadmill exercise duration of 576 seconds. After 40 weeks of treatment, mean exercise duration rose to 672 seconds, or a 16.7% improvement.
The placebo patients began the study with a mean, baseline treadmill exercise duration of 588 seconds and ended at 616 seconds, or an improvement of 4.8%.
That works out to a placebo-adjusted improvement in exercise duration for Ampligen of 11.9%. This benefit doesn't appear to be statistically significant, however. The study, as published inPLOS One, makes no mention of this intra-group comparison reaching statistical significance.
The Ampligen study appears to have failed -- which gibes with the FDA's decision to reject the drug and call for a new study to be conducted.
Hemispherx has not invested the money and time necessary to run a new Ampligen study, choosing instead to change the way the primary endpoint of treadmill exercise duration was measured. Instead of comparing the two groups of Ampligen and placebo patients, Hemispherx switched to analyzing the exercise data using each individual patient as their own comparator.

My bold
http://www.thestreet.com/story/11720256/2/hemispherxs-ampligen-rehash-unlikely-to-impress-fda.html

 

[kaffiend]

Barbc, I have no interest in Ampligen as I don't think it would be an effective drug for me, but the statistics in that PLoS One paper are solid. That guy from thestreet.com has a degree in political science and appears to have an ax to grind with hemispherx biopharma. He clearly does not know how to read or report on a scientific journal article.

"Thisbenefit doesn't appear to be statistically significant, however. The study, as published inPLOS One, makes no mention of this intra-group comparison reaching statistical significance."

Table 1 of the paper gives the results of a paired t-test comparing whether the change from baseline is equal to zero within each treatment group p<0.001 (rintatolimod) and p=0.198 (placebo). The week 40 results for exercise tolerance comparing rintatolimod vs placebo were also statistically significant with an analysis of covariance model using the baseline scores as a covariate (p=0.047).

Hemispherx probably went wrong by reanalyzing existing data rather than running a new study and using the analysis published in PLoS One. There is however, absolutely nothing wrong statistically or design-wise with comparing each patient to their own baseline data - it's called a repeated measures or paired samples design.

 

[mellster]

You cannot cite anything from Adam Feuerstein. He has no expertise in the medical field but he is generally bearish on small cap pharma stocks and their drugs which makes sense as the majority of those fail and so he will always appear more right than wrong. He may or may not also have friends that short-sell said stocks before/upon his publications.

 

[barbc56]

The study changed the endpoints, which I believe was a criticism of the PACE trial. The statistics compared individual differences and not group differences.

In my opinion and from what I do know about statistics, this makes the study problematic and further research is needed.

Barb

 

[Guido den Broeder]

IMHO, a new study on Ampligen should combine it with appropriate antivirals, like valacyclovir.