The Food and Drug Administration (FDA) will once again
decide this winter whether the experimental drug Ampligen, which has helped
many ME patients recover or improve, should be approved. Should the drug be approved, it will be
an ME game-changer.
Oddly, little has been discussed on the boards about
Ampligen this time around—perhaps because the drug’s been up for approval
several times before—and that’s too bad, because an approved drug would help
legitimize the disease, provide much-needed treatment for patients, and signal
to other drug companies that the disease is worthy of effective medications—and not psychobabble.
Eighteen years ago, I wrote a piece on Ampligen for
Philadelphia magazine called The AIDS Drug No One Can Have. Back then
the drug proved remarkably helpful for both ME and HIV/AIDS. Many patients went from bedridden to
returning to work and school and a few with ME whom I interviewed who’d been
ill for only a few years completely recovered.
Then the FDA pushed for a change to make the
intravenous drug easier to administer; it’s not clear if the new formulation is
as effective, but many patients have continued to report improvement.
The FDA has tentatively scheduled the review process to
begin December 20 and to continue to February 2.
In the meantime, the FDA wants to hear from patients by November 1 about their experiences with ME, including how drugs like Ampligen have helped in treating the disease. The FDA is also interested in learning about the emblematic endpoints that should be used in reviewing ME drugs for approval. Fatigue, for instance, is a a subjective and often inaccurate marker with ME. Improvement in post-exertional malaise would be a far more significant marker.
Patients can submit comments about Ampligen to the FDA directly here or send in comments and I'll post them on CFS Central and forward them to the FDA. Pressure needs to be placed on the government so that these agencies will be forced—kicking and screaming—to do the right thing by patients.
In the meantime, the FDA wants to hear from patients by November 1 about their experiences with ME, including how drugs like Ampligen have helped in treating the disease. The FDA is also interested in learning about the emblematic endpoints that should be used in reviewing ME drugs for approval. Fatigue, for instance, is a a subjective and often inaccurate marker with ME. Improvement in post-exertional malaise would be a far more significant marker.
Patients can submit comments about Ampligen to the FDA directly here or send in comments and I'll post them on CFS Central and forward them to the FDA. Pressure needs to be placed on the government so that these agencies will be forced—kicking and screaming—to do the right thing by patients.
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I received Ampligen for 6 months (9/90-4/91) and for 12 months (1/92-1/93). Ampligen was efficacious for everyone I knew receiving it. The following are the documented improvements for me while taking Ampligen:
ReplyDelete1. My productive hours per day improved from about 3 or 4 to approximately 7 to 9,.
2. IQ improved from 124 to greater than 134,
3. Alpha Interferon, which is produced when viruses invade cells, decreased from 460 to less than one (extraordinarily high to normal),
4. T4-Lymphocyte numbers increased from 846 to 1817,
5. T8-Lymphocyte numbers increased from 414 to 674,
6. B-Lymphocyte numbers increased from 188 to 401,
7. Natural Killer Cell numbers increased from 14% to 34%,
8. Natural Killer Cell activity increased from 7.4% to 8.4%,
9. Ability to perform pre-selected tasks improved from 59% to 71%.
My pain reduced to the point that I realized I had a hernia which had not been recognized due to groin lymph node pain and swelling caused by CFS. After 4 months of receiving Ampligen I could exercise without exacerbation of my CFS symptoms. I was not able to do so before receiving Ampligen despite years of trying to gradually increase my exercise capacity.
Other CFS symptoms that improved while I received Ampligen vastly increased my quality of life. These are a few examples. Short term working memory, hand to eye coordination, and my cognition improved. I could dial a phone number the first time, rather than the three to four times it took due to memory loss, or because of inadvertently pressing wrong keys. Short term memory improvement enabled me to cook without burning food or forget to turn off burners, draw bath water without flooding the house, and not lose my car in parking lots.
I was considerably more efficient in completing tasks because I was not constantly losing my train of thought. I was able to read without continuously going back to reread sections of paragraphs I forgot. My increase in coordination and cognition made it easier and more pleasurable to walk and drive because it required significantly less concentration and vigilance not to fall or have an accident. Visual acuity fluctuations diminished. I could tolerate a larger range of ambient temperatures without becoming uncomfortable. The frequency and intensity of my headaches lessened. Spontaneous bruising on my body stopped so there was less tenderness. Dryness and irritation of eyes, nose, and mouth declined. Stiffness and soreness of joints was reduced.
My heightened health, ability, and dependable mental and physical stamina made planning and participation in daily events a great deal more successful and enjoyable."
Thank you, Mindy, for posting this information. I have not had the opportunity to receive Ampligen, but I believe there is no good reason the drug should not receive immediate approval. It is a disgrace that FDA approval has already taken so long.
ReplyDeleteDoogle, what a great comment! I hope the FDA will listen to the experiences of real people who have taken the drug and approve it as soon as possible. Thank you for sharing your experience, Doogle.
Thanks, Mindy! What was changed about Ampligen's formulation and why? Do you think the changes may have impaired its effectiveness?
ReplyDeleteI have never had Ampligen but wanted to comment on the monitoring of ME to assess if improvements is happening. I use a 3d pedometer and I have found it invaluable for monitoring how much physical activity I do each day. It shows very clearly the effect of post exertional malaise because after I have over done things I naturally reduce my activity levels while recovering. Also it is really obvious when I have crashed for whatever reason and it is easier to see what the baseline that I can manage is. If I ever got an effective treatment I would expect that baseline activity level to rise naturally without causing post exertional crashing. It is so obvious if you plot a graph. If only there were an equivalent for mental and emotional activity it would be easy to track all activity improvements.
ReplyDeleteMy experience with Ampligen is that I have been yearning to try it for decades. I have read with envy and admiration the stories of those who have been able to get it, and with extreme sadness that only politics have kept this drug out of the hands of doctors and patients who would dearly love to see if patients could get even a part of their lives back with this drug. The FDA has not done us any favors by not approving this drug, the only one proven to help some patients, for so many years. I can only hope that this time FDA will do the right thing.
ReplyDelete-Lilly C
Hello Lilly,
DeleteMy name is Rich W from Reno/Tahoe.
Please consider that the drug manufacturer is obliged to meet FDA rules and cooperate with their requirements. Then umbrella this with personalities.
I try to imagine this two-decade relationship with the U S government, but who would want to?
I agree. Hope for the approval!
Thank you Doogle. Did you submit that?
ReplyDeleteThanks Mindy. I hope that all who have used AMpligen will submit their experiences. The docket number to use with your submissions is FDA-2012-N-0967. The page is confusing - says the # is at the top and it's not. It is in the sidebar however, and I've confirmed with teh FDA that this is the correct #.
ReplyDeleteAlso - the meeting is Oct 25 & you ahve to register for it (from the righthand sidebar) "Submit either electronic or written comments by November 1, 2012. The public meeting will be held on October 25, 2012, from 9 a.m. to 12:30 p.m. Registration to attend the meeting must be received by October 18, 2012. See the SUPPLEMENTARY INFORMATION section for information on how to register for the meeting."
Finally, The Street panned Hemispherx's chances of approval today, which for me, emphasizes the need for testimony from everyone who has had direct experiences with the drug if possible. Here's the link to the article, http://www.thestreet.com/story/11720256/1/hemispherxs-ampligen-rehash-unlikely-to-impress-fda.html
My doctor, Dr. Charles Lapp, is running a trial of Ampligen, but since it is a clinical trial with a very strict protocol and like many people with ME, I have positive ANA, I was excluded from being able to participate in the trial. Thus I was denied access to the only promising treatment for this unbelievably debilitating condition. I have heard through other patients the many success stories, and living with a disease in which there is so little hope (NO treatments, NO cure, nothing...), when something finally comes along which could make a difference, it is cruel to deny that hope to the estimated one million ME suffers in the US alone. I have had ME for 21 years now, and have steadily declined during that time from a competitive athlete and ambitious, educated professional to a bed bound invalid. I grieve every day for the life I have lost, but I am far from being the only one in this position. If Ampligen was approved, I might have a chance to get at least some of my life back, which would mean the world to me. Please approve this drug for the treatment of ME/CFS as soon as possible. Thank you for listening.
ReplyDeleteI will be submitting a formal statement, but I wanted to say something here. All FDA has ever looked at is "double-blind" trials. I could not be in the double-blind because I was way too sick, judged a 30 on the Karnovsky scale of 1-100, mainly bedridden, beset with immune defects and viruses. But I was precisely the sort of case they should have been looking at. It's my hope that this time they WILL look at me.
ReplyDeleteOn Ampligen, I have a life. Off of it, I don't. It's that simple. I can talk and be understood; I can hear and understand what is said to me. I can WALK. I can drive a car. I can read a book and I've published essays. I don't suffer constant pain behind my eyes or in the back of my neck, nor splitting headaches.
When I first started Ampligen in Feb. 1998, I was positive for the 37kDa Rnase-L and HHV-6A. After six months on Ampligen, they were gone. My symptoms had already improved dramatically. I went off in Oct. 2000, but relapsed severely on Oct. 6, 2001 with a blackout. The symptoms and biomarkers returned.
Six months after restarting in May 2002 the markers were gone, but it took longer this time to regain equilibrium. My family decided it was unsafe for me to go off it, so we used my disability check for Ampligen and I lived off my husband's income. Obviously few of my friends could do that. By 2006 flew to London by myself for the first Invest in ME conference and walked around the city. I went hiking with my brother in the summer of 2007. I wrote most of my 650-page book manuscript.
Then, suddenly, I lost the drug in Feb 2008 when the head of my practice died. By Sept 2008 I had collapsed.
I went out to Tahoe to see Dr. Peterson, and he tested me thoroughly. My natural killer cell function was down to 2-3%. The 37kDa Rnase-L returned. I had an abnormal SPECT scan and very abnormal VO2 MAX (CPET) scores, and abnormal cytokine patterns. But the viruses! I started with EBV (as I always had before), but I also had CMV, HHV-7, and Coxsackie B. By the summer of 2009, CMV and HHV-6 were in my spinal fluid.
Hemispherx has never been able to use these viruses and biomarkers in their double-blind studies because the immune tests aren't accepted and the viruses can be hard to find (even with me). Not to mention the cost! Without that, it's hard to measure the real, profound progress - or understand that improvement can take a while and proceed slowly.
I went back on it in March 2010, but I had to live 3000 miles away from my husband of 35th years. I can get it in NYC now, tho I have to commute 100 miles by train twice a week. I have a life again.
If they pass Ampligen, more patients will finally have access to it - tho it won't help everyone. You can get it at home. And we will no longer be limited in the studies we can design. We can try a lower dose of Ampligen with, say, a lower dose of Valcyte or even Vistide. We can move on to new ideas.
If we lose, it goes away. Poof. I pray we don't lose.
An error: I began Ampligen on Feb. 4, 1999, not 1998.
DeleteThis comment has been removed by a blog administrator.
ReplyDeleteHi Joe,
ReplyDeleteThe formula was changed to make it easier to administer. The old Ampligen formula had to be heated and then cooled to room temperature before being administered. The FDA thought that was too complicated and was concerned with quality control, which ultimately rested in doctors’ offices and not with the manufacturer.
Perhaps the best way to know if the drug is as effective now as it was in its previous incarnation is to hear from people who’ve been on both the old and new formulas. If any of you are out there, consider posting your comments. They’d be deeply appreciated.
I also wonder if the FDA would have pushed for a procedural change had Ampligen been evaluated for treating cancer, Parkinson’s, Multiple Sclerosis or HIV/AIDS.
Mindy and Joe,
DeleteThe new formulation was approved by FDA circa 1998. This frozen drug simply needed thawing by site administrator. Then deliver via IV. Mindy surrounds this information very well, above.
Concerns of fellow seriously ill 501 participants was zero to high; we were in high-end cost-recovery venue, seeing the first improvements ever and you want to change something? I have a letter from Bill Carter at HEB (Hemispherx Biopharma) reassuring that frozen Ampligen was otherwise the same thing as reconstituted. One of five in our group stayed with the generalized belief that frozen was not as effective.. After a month or so he abandoned this idea. Later he said he was not seeing worthwhile results from Ampligen and left the program. The rest in the group accepted science and never remarked of any difference between formulations. We did not titrate up with the new version; we crossed formularies at par, instantly.
We had received one year of drug at that point.
Finally, given CFS memory, the story line above is pretty solid; the dates are not certainty and could vary within a nominal range. This should not affect interpretation.
People make the FDA out to be the villain in regard to Ampligen but you know the old saying, 'Be careful what you wish for.' As a person with ME/CFS, I would like a medicine that is effective and safe as soon as possible but from reviewing the few Ampligen published papers, talking to people who've gotten better on Ampligen and those who have not, as well as non-patients that have been involved with the trials, I don't think Hemispherix has been forthcoming about which patients benefit, how much the average (and not anecdotal) patient benefits, and what the short-term or long-term effects of Ampligen are. There are no laws that Hemispherix has to release all their data to the government or the public. My concern is, were approval to happen, sure, some people might benefit but without all the data, some people might come to harm as well. Concerning the ANA, at least one person publicly reported that they had a developed an autoimmune illness while on Ampligen. While the illness was not attributed to Ampligen, who really knows without complete data from the company? In any case, that might be the reason why having a positive ANA is considered exclusion criteria.
ReplyDeleteI have a positive ANA. And I've been in the open-label (means you have to pay for it) Ampligen study since 1999, give or take three-four years in there. Either it's something that Dr. Lapp is doing differently, or you are referring to the double-blind study, in which a positive ANA might be exclusionary because it would be indicative of autoimmune disease.
ReplyDeleteMy positive ANA is due to Hashimoto's thyroiditis, which appeared about a year into my collapse with the disease. It correlates with HHV-6A, because, apparently, the immune system can't get to HHV-6A to take it out, and thyroid molecules resemble HHV-6 molecules. So it actually gets better on Ampligen (but I am stuck with hypothyroidism either way.)
One of the reasons we need to get Ampligen past the Phase III is that the FDA only allows studies that go through the company. It's really time we had other people designing studies, I think.
One thing that is crucial in my mind, especially after hearing negative patients’ reports, is that the amount of experience of the principal investigator with Ampligen cannot be overestimated. Dr. Dan Peterson in Incline Village has by far the most experience with this drug (probably even with this illness). The number of patients he has treated with Ampligen is exponentially higher than any other physician’s and so is his success rate with the drug because he knows which type of patient is likely to respond to Ampligen. He also, very importantly, starts patients off on a low dose and slowly works up to a dose that is individualized for each patient. This is not an antibiotic or another drug that can be given at a standard rate. The drug is designed to get the immune system to a tipping point of being able to function more normally again. That tipping point is reached by every patient at a different dose. When one hears stories of patients who quit the drug because of bad side effects, one should ask what dose they were on because often, they started at, or were quickly moved up to, an insanely high dose. No wonder they had a negative experience with the drug. And when one hears stories about patients who did not respond to Ampligen, it typically turns out that they were not patients of Dr. Peterson, although I am sure he has had cases, too, that weren’t a success, but it seems rarely and a lot less often than any other physician. The FDA needs to make it a priority to tap into Dr. Peterson’s vast knowledge and experience regarding this drug. What if most or even all of these negative experiences are not caused by the drug, but by the incorrect administration/dosing of the drug or by selecting patients who were not good candidates for the drug in the first place? Wouldn’t it be a tragedy if the patient population who has not had a chance to get on a proper Ampligen treatment protocol were to reject drug just because of anecdotal stories that are not representative of the safety and efficacy of the drug?
ReplyDeleteIf big pharma were applying for a drug approval and the data wasn’t complete, as has been claimed about the Ampligen trials, would the FDA just deny the application or would they work with the big drug company to get to a resolution? Hemispherx is a small company with few resources. If they had the money to run a 300-patient randomized, double-blind, placebo-controlled trial, they would jump on in because they have an excellent drug with a huge potential market.
Maybe Hemispherx is an eccentric drug company and has made mistakes in the past. I don’t know. But is this an excuse for the FDA to basically take out their frustration on the patients by not approving the drug? I think not, especially if the drug in question is very promising and safe and the only one on the horizon for a debilitating disease that has no other approved drug treatments.
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ReplyDeleteWhether or not one is receiving the benefit of Ampligen, this is a pivotal moment for all ME patients. There could be no more powerful signal sent to those who claim that we are not really sick than having an immune-modulating drug FDA-approved for our disease. Getting approval for Ampligen would open the floodgates: The CDC and NIH would have to start funding more research. The mocking by the media would stop. The mistreatment by the medical community would cease. Insurance companies would have to start paying for the drug and others who would come on the heels of Ampligen’s approval. Disabled patients would not be as easily cheated out of their disability benefits. The domino effect would be tremendous. If Ampligen doesn’t get approved this time around, I fear that will be the end of the drug and of this unique opportunity for the patient community. There may not be another one like this for years or decades. The FDA is closer to approving this drug than it has ever been, but, unfortunately, I believe the chances to be no better than 50/50 at best. This is why we need to keep and turn up the pressure. Remember Dr. Lipkin encouraging us to be aggressive and make noise? Let’s do it!
I am currently enrolled in the Ampligen opne-label trial and I am a responder. Ampligen has stopped the disease progression, which had become really scary because I was declining rapidly. On some days, I was hardly able to walk anymore and climbing stairs was out of the question. On Ampligen, more than anything else, my post-exertional malaise has improved. I have better stamina. On good days, I can push my activities a little further without paying a huge price. My multiple chemical sensitivities have improved. Exposure to small amounts of chemicals, fragrances, etc., doesn’t always give me an instant migraine, nausea and cognitive problems anymore. Orthostatic intolerance has improved. On good days, I don’t start getting symptomatic after only a couple of minutes of standing anymore. Depending on the kind of day I have, I can stand fairly comfortably between 5 and 20 minutes. On some days, I am able to take short (10 minute) walks, when before I could hardly manage to walk a block. I also don’t experience shortness of breath as frequently or as easily triggered as I used to. However, crashes still do happen, but they are often (though not always) less severe than in the past. If I do crash, I recover more quickly. My quality of life has drastically improved on Ampligen and I expect continued improvements over the months, maybe years, to come.
ReplyDeleteI became ill with CFS about 3 years ago after an acute viral onset. I have been enrolled in the Ampligen open label trial for 3 1/2 months. There is no question in my mind that the drug is biologically active because it intensifies my symptoms post infusion for a period of up to 24 hours, but more importantly, it has lead to an expansion of my "energy envelope" to the point where I only have to nap about twice weekly (instead of five times per week) and I am able to exercise judiciously without crashing. My sleep has improved somewhat and I have been able to reduce my use of soporifics, and am considering work part time. More objectively, my T3, CD4, and NK cell counts (all of which were low) have doubled! I am amazed at the degree of subjective and objective improvements and I look forward to more of the same over the coming months.
ReplyDelete