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Ampligen On the Clock: Hemispherx's 'Complete Response' Means Ball is Now in FDA's Court Now

[caption id="attachment_12929" align="alignright" width="325" caption="By end the January, 2013, at the latest,we will know if the FDA will approve Ampligen for ME/CFS..."]
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Moving quickly, Ampligen's producer, Hemispherx Biopharma, filed its 'complete response' to the FDA's request for data just 53 days after the agency agreed to relax its requirements for review of the drug. Hemispherx's 'complete response' means we will know by the end of January and perhaps sooner whether Ampligen becomes the first FDA approved drug for chronic fatigue syndrome (ME/CFS).

New Data

In its response Hemispherx provided new data derived from a 24 week extension period occurring after the 40 week original trial. Hemispherx stated the data will show that patients who remained on the drug for a further 24 weeks showed further improvements in endurance (23% - 39% increase in treadmill duration) suggesting that the drug's effectiveness increases over time.

Similarly, Hemipherx reported that patients who responded well to Ampligen showed significantly greater improvement relative to non-responders in areas such as vitality, general health, Karnofsky performance (functionality) and activities of daily living the longer they were on the drug. This is important because the original study did not highlight improvements in functionality and well-being. This data suggests Ampligen works 'globally' to improve both endurance and functionality.

FDA and Ampligen

It appears that the FDA has at least several possibilities;
  • it can approve the drug
  • it can reject the drug
  • it can give the drug 'accelerated approval' status - in this scenario Ampligen is not approved but Hemispherx is allowed to market the drug and gather more data for a final attempt at approval
  • it can ask Hemispherx for more data - without the income derived from 'accelerated approval' this outcome would be difficult for Hemispherx.
Hemispherx's Press Release suggests the company is gunning for accelerated approval status. While the FDA did recently substantially relax its requirements to consider Ampligen for approval its possible, perhaps even probable, they still want that large, multi-dose, placebo-controlled, double-blinded treatment trial originally required in their 2009 report. Hemispherx didn't come anywhere near providing that kind of data but getting accelerated approval would give them the means to do so.

The FDA has increasingly come under fire to approve more drugs and, in particular, to approve more drugs for chronic illnesses and the new law provided drug companies an opening to do just that.

New Law Presents Opportunity for Hemispherx and Ampligen

In their press release Hemispherx highlighted the fact that the 2012 Food and Drug Safety and Innovation Act (FDSIA) law encourages the FDA to take 'innovative and flexible approaches' to assessing treatment for 'serious' disorders with 'unmet' needs.

In section 901 from the FDASIA Act below note the emphases on 'expedited...review' and the need to target subpopulations.

"the FDA should be encouraged to implement more broadly effective processes for the expedited development and review of innovative new medicines intended to address unmet medical needs for serious or life-threatening diseases or conditions... This may result in fewer, smaller, or shorter clinical trials for the intended patient population or targeted subpopulation
Patients benefit from expedited access to safe and effective innovative therapies to treat unmet medical needs for serious or life-threatening diseases or conditions.​

Indeed, recent history suggests a drug need be effective in only a small group of patients if if few treatment options are present. With FDA analyses suggesting that 11 lupus patients needed to be treated on Benylstra to find one the drug helped, and with the drug showing marginal effectiveness overall, but with the last FDA approved drug for lupus dating back 50 years, Benylstra was easily approved. (Benlystra significant helped those few patients which responded.)

Hemispherx's production facility at New Brunswick will be undergoing 'pre-approval inspection' as part of the FDA review process. If the drug is approved or granted accelerated approval status Hemispherx should, hopefully, be able to hit the ground running. Could the drug be widely available to ME/CFS patients sometime next year? Time will tell.

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Comments

Hope123 says: "Overall, I think there will be better drugs than Ampligen, safety and efficacy-wise, in the near future and I would caution people to not push for a "political victory" without regard to safety."

I am frankly astonished by how skeptical some in the patient community are about Ampligen and how optimistic they are that something better will be invented in the "near" future.

I'd like to remind you that many of us have been ill 20 years or longer, and have heard the line that a treatment is just a few years away many times before. CFS is extremely difficult to treat and there are no known molecular targets. Drug companies are afraid to start. As of now, no drug company other than Hemispherx has a novel candidate drug even in phase I or II for CFS. When a target is identified, it will take five to ten years to go through the full clinical trials process. If Ampligen doesn't get approved and you are 20 years old and are disabled by CFS, that means you may be in your 30s before "something better" comes along.

The "near" future in scientific terms really means a long, long time in real human life terms.

And that something else may not be better. There is the idea of repurposing existing drugs like rituxan, but it is well known that rituxan can cause death. Existing antivirals carry the risk of organ damage, infertility, and death if they are not carefully monitored.

Ampligen should have been approved for CFS back in 1998, if not earlier. There was strong evidence then that it improved all the symptoms of the condition in the majority of treated patients with severe disability and as far as we know it is safer than any other known immunomodulator.
 
I hope there are better drugs out in the near future but I would be surprised if there are significant safety issues with Ampligen as Dr. Peterson said in a recent interview with Llewelyn King, I think, it was...that it is safe and effective. He's been giving it to patients for over 10 years...

Some people seem to do well after Ampligen - they stay at their level of wellness - but others relapse. It can take a couple of years for them to relapse or it can happen more quickly...

I see Ampligen as a bridge to something better; once they can start studying it in more detail they'll know better why it works in some patients and not others; that will give researchers a leg up on the next drug...but its got to get in there first....
How can a doctor be prescribing a drug that is not FDA approved to patients for 10 years? Have I missed something only I thought Peterson was doing so in trials only, but regardless I would like to understand more about how such a thing could happen. Isn't the whole point of Ampligen trying so hard to gain this approval that they can then be offered to one and all legitimately? If Ampligen can be prescribed now, then what's the point? Sorry. I'm not familiar really with the way this works in the USA.
 
Morning Sato,

I am frankly astonished by how skeptical some in the patient community are about Ampligen and how optimistic they are that something better will be invented in the "near" future.

I'd like to remind you that many of us have been ill 20 years or longer, and have heard the line that a treatment is just a few years away many times before.
Speaking personally and as someone having had this diagnosis now for 15 years, my scepticism is as a result of having this condition for 15 years.

I have grown used to false starts, false promises, false hope, and therefore I'll believe it when I see it/can try it myself once it has been approved.

Absolutely nothing wrong with scepticism but, don't get me wrong, I am at one level quite delighted to hear of any drug being manufactured specifically for my use - but Ampligen wasn't not originally.

If it works, it works, if it doesn't well I won't have lost any more sleep about another failed promise of help.

Generally, I am very very cautious about any drug that claims it can help such a diverse patient group even one that employs the 'best' criteria currently known.

That said and like I mentioned above, if it does find it's way into my doctor's list of approved thing to try, I shall most definitely take it for a work-out and myself too if the claims hold up.
 
Hemispherix makes Immunovir. It was prescribed to me. It isn't covered by any insurance, you have to order it from Canada, and I didn't notice any benefit after taking it for a long time. I hope Ampligen works better.
No. Hemispherix does not/never made Immunovir to my knowledge. Immunovir was developed and produced by Newport Pharmaceuticals Limited and their subsidiaries. http://www.rivexpharma.com/products_imunovir.html
 
Here is hoping for ‘accelerated approval’ status!
 
How can a doctor be prescribing a drug that is not FDA approved to patients for 10 years? Have I missed something only I thought Peterson was doing so in trials only, but regardless I would like to understand more about how such a thing could happen. Isn't the whole point of Ampligen trying so hard to gain this approval that they can then be offered to one and all legitimately? If Ampligen can be prescribed now, then what's the point? Sorry.
Ampligen has been used in the US for over 20 years outside of FDA approved double blind studies under Investigational New Drug (IND) status. "Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and the FDA review takes place." http://www.fda.gov/drugs/developmen...estigationalnewdrugindapplication/default.htm

The length of time this has occurred is rather unique as far as I know, and is due to the political problems with the illness and Hemispherix. The FDA has not wanted to shut down access to the only drug that has ever shown promise for treating ME/CFS. Yet the FDA doesn't want to approve it for general marketing until they conclusively know the benefits of the drug clearly outweigh the risks.

A treatment IND only allows a limited number of people to be on the drug. I believe the treatment IND Hemispherix has from the FDA allows 100 persons. The sites giving the drug have to go though a lengthy approval process and theoretically the drug company can only recoup their cost of manufacturing the drug. Right now it costs approximately $15,000 per year for the maximum dose, 400mg. IV infusion costs are extra. Most Insurance will not pay for a drug given under a treatment IND because it's still classified as experimental.

So there are severe limitations for use of the drug under the present process hence the necessity to get full marketing approval.
 
Like satoshikasumi, I can't wait another sixteen years, or six years, or maybe even another six months for a real treatment. How many of us will be dead from this illness by the time the FDA gets off its ass and makes a decision?

My life has already been destroyed. If a treatment killed me quickly, that would be an improvement over dying a little each day. Right now my bank account and my ability to perform activities of daily living are in a race towards zero. My only income is food stamps, and the ground is rising up to meet me at a terrifying speed. Since I live in the US, there is no safety net and I have no parachute. But we have 'freedom': we're free to starve under a bridge, except the cops will run us off, since it is still a crime to be penniless in public!

My application for Social Security disability is celebrating its fifth anniversary. It's now old enough to enter school, except public education is also being wrecked. No one can tell me when I will get scheduled for an ALJ hearing. If I manage to live long enough to get a hearing, the chances of winning my claim are not good.

Meanwhile Governor 'Bully' LePage never misses an opportunity to insult and attack Mainers with no money. His latest plan is to 'reduce energy costs' by getting rid of the tiny fee on electric bills that funds a program to help poor people with their electric bills. Last year that program paid all of $120 to my account. An undeserved bonus for sure!!
 
I know I am being somewhat of a bulldog for Ampligen. But I am one of only about a hundred patients who has actually taken Ampligen during the past five years. We, the privileged few, know that this drug is unique. It gave me back my mind. My cognitive function.

The FDA knew Ampligen could dramatically reduce the severe debilitation associated with CFS back in 1998, when the phase II results were released. They chose not to fast track the drug for approval, in spite of the fact that these desperate patients had no other hope. At the time FDA made this decision, CDC and NIH officials publicly expressed skepticism about whether CFS was a real disease, and the view that it was a psychological or imaginary ailment was held by many doctors and government officials.

Up until just a couple years ago, the CDC website had a detailed statement advising doctors not to order tests that could document CFS patients' disability. They said not to order tests for herpesvirus infections, not to do immune panels, not to look at natural killer cell function, not to do tilt-table tests, not to do brain function tests, claiming that none of these things had any value in diagnosing or treating CFS.

But, the treatment section of the CDC site did and still does list psychotherapy: cognitive behavior therapy, and graded exercise therapy as the first treatments to be tried. Ask patients in the UK and EU countries how well that approach is working for them.

In the 14 years since, no other drug company has dared to even try to develop a drug for CFS, in spite of the fact that the profit potential is huge. With Ampligen, the FDA has repeatedly sent Hemispherx on fishing expeditions to try to find something wrong with the drug- a new rodent carcinogenicity study, a new evaluation of cytokines to look for evidence that the drug induces autoimmunity. Each test looking for the ghastly side effect comes up empty-handed. Ampligen has been used in humans with CFS for more than 20 years, and some individual patients have taken it for 10 years or more of their lives because nothing else works. No one has died from Ampligen.
 
My life has already been destroyed. If a treatment killed me quickly, that would be an improvement over dying a little each day. Right now my bank account and my ability to perform activities of daily living are in a race towards zero. My only income is food stamps, and the ground is rising up to meet me at a terrifying speed. Since I live in the US, there is no safety net and I have no parachute. But we have 'freedom': we're free to starve under a bridge, except the cops will run us off, since it is still a crime to be penniless in public!
My heart goes out to you jimells, your post has really touched me. I am glad that you are here sharing your frustration and pain with us, I hope that we can give you some comfort. Know that you are loved.
 
if approved by the FDA, any doctor would be free to prescribe Ampligen for any condition (off-label prescription is perfectly legal in USA).

Insurance coverage in the USA would work like this: most companies have a formulary listing covered drugs. There's probably a requirement that they have a comprehensive listing (and it would be to their benefit to do so, anyway), so it would be difficult for them not to include a drug for a condition which has no other approved treatments.
However, if they do not cover brand-name drugs on a specific plan, they might not have to cover it until there is a generic version (though it's possible they could make an exception; some insurances will do this but that's more likely if one has group insurance through someone's work).
Your doctor still needs to convince the insurer that the treatment is 'medically necessary' for you specifically (whether because you have a diagnosis it treats, or for some other reason).

In other countries such as Australia, the drug may have to be approved for a specific condition in order for insurance to cover.
 
AMP 511 Cost-Recovery treatment protocol requirements are expensive:

* The total cost of Ampligen to a participant is approximately $2,500/month.

* Ampligen is administered from 200mg or 400mg vials. The cost of the Ampligen alone, at the maximum therapeutic dose of 400mg twice per week, is $2,400 per 8 weeks, and is rarely covered by medical insurance. Some patients may require the lesser 200mg dose which is less expensive.

* IV Infusion costs, administrative costs, and testing are extra and estimated at $2,000 per 8 weeks and are generally not covered by insurance.

* Dr. Patel estimates it will take 18 months for most patients to achieve the full therapeutic and stabilization effects of Ampligen, and they should plan for that timeframe.
* Before being enrolled in the treatment protocol, patients will be
tested for biomarkers to determine the likely response to Ampligen.
However, Ampligen has been clearly beneficial for a subset of ME/CFS patients. Some of the
clinical factors that may identify these patients are:

* Acute Viral Onset

* 2-5A Synthetase/RNase L Up Regulation

* Depressed Natural Killer Cell Cytotoxicity

* Persistent Herpes Virus Infections (EBV, HHV-6, CMV, etc)

Ampligen often initially causes dose dependent flu-like symptoms that can be significant. This has contributed to patient reports of Ampligen's adverse effects.

These are not the only health risks from Ampligen.

Titrating the Ampligen dose may help minimize side effects.
Ampligen is administered intravenously twice per week, so people with fragile veins may have difficulty with infusions.
IV ports are sometimes installed.
Well at least it affords more insight into the clinical application of this drug and it's cost etc.
 
So the FDA have accepted the submission from Hemispherex. Share price was up 10% on the news it seems - or it was - remains 3 cents off it's 52 week high of 51 cents but if approved then.... who knows? Fancy a punt anyone?

http://www.virtual-strategy.com/2012/08/14/fda-accepts-complete-response-submission-regarding-ampligenr-new-drug-application-chronic
 
Hope123 says: "Overall, I think there will be better drugs than Ampligen, safety and efficacy-wise, in the near future and I would caution people to not push for a "political victory" without regard to safety."

And that something else may not be better. There is the idea of repurposing existing drugs like rituxan, but it is well known that rituxan can cause death. Existing antivirals carry the risk of organ damage, infertility, and death if they are not carefully monitored.
I agree we should have had Ampligen decades ago. It could have now become generic and hence cheaper. The delay in approval has robbed two generations of patients of a chance at some recovery, and will rob another two generations who do not have the cash to pay for it once it goes commercial.

However Rituximab is not particularly dangerous (especially if it can cure rather than treat), though not particularly safe either:

http://arthritis-research.com/content/pdf/ar3337.pdf

The death rate is about 3%. Much of that is from infections. Some of it is from a severe infusion reaction. However we have yet to see either in CFS or ME patients, unless I missed an announcement. We are a different patient set. On the other hand, so far not enough patients have been studied to reliably show even a 3% death rate. On the third hand, for any Moties fans out there, drugs have been withdrawn from market for death rates lower than this.

Bye, Alex
 
They mention that patients with depressed natural killer cell cytotoxicity have better chances of responding to Ampligen. Is this lower number of natural killer cells, or is it a different thing?
 
They mention that patients with depressed natural killer cell cytotoxicity have better chances of responding to Ampligen. Is this lower number of natural killer cells, or is it a different thing?
It's almost the same thing, Tally, but "depressed natural killer cell cytotoxicity" specifically means low function, rather than low numbers. But I suppose that low function can be caused by low numbers.
 
Here's some info about the effectiveness of Ampligen.

A Double-Blind, Placebo-Controlled, Randomized, Clinical Trial of the TLR-3 Agonist Rintatolimod in Severe Cases of Chronic Fatigue Syndrome
David R. Strayer et al
March 14, 2012
PLoS ONE 7(3): e31334. doi:10.1371/journal.pone.0031334
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031334



And here is a helpful summary:

ME Research UK - Breakthrough Magazine:
Autumn 2012 issue, page 12, third column, under 'Maryland':
http://www.meresearch.org.uk/information/breakthrough/index.html

Rintatolimod trial
Clinical trials of non-psychological treatments
are quite rare in ME/CFS, so it can be
exciting when one comes along, particularly
if the most severely affected patients
are included. One recent example was
a phase III randomised trial in which the
TLR-3 agonist rintatolimod was compared
with placebo in 234 people suffering
with long-standing, debilitating ME/CFS
at 12 different centres across the USA.
After 40 weeks, exercise tolerance (total
achievable exercise time on a treadmill) was
significantly improved in the patients on
intravenous rintatolimod therapy (400 mg
twice weekly) compared with those on
placebo. The size of the improvement was
around 20%, equating to approximately
68 seconds of additional treadmill activity.
Indeed, the authors say that this level of
improvement represents approximately twice
the minimum considered medically significant
by regulatory agencies. Rintatolimod also
reduced dependence on symptom-relieving
drugs compared with placebo, and it seems
to have been well-tolerated with no serious
adverse effects definitely related to the drug.
Under its more common name, Ampligen,
rintatolimod has been well-known to ME/
CFS patients since the first preliminary report
of its potential usefulness in 1994. Ampligen
has known antiviral and immunomodulatory
properties, and these positive results
suggest that it may become part of the
therapeutic armoury of treatments for ME/
CFS, providing FDA approval is finally granted.
 
Tell the FDA what your experience with Ampligen has been.

http://www.cfscentral.com/2012/09/what-have-your-experiences-been-on.html?spref=fb

TUESDAY, SEPTEMBER 25, 2012




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 insisted on a formula 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 directlyhere 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.