Ampligen: FDA Approval DENIED 12/1/2009

[parvofighter]

Devil's Advocate

I'm going to play Devil's Advocate here.

I do wonder whether the FDA rejection was in fact necessary, in fact essential in light of the recent XMRV findings. Keep in mind that determination of "Efficacy of Ampligen for treatment of Chronic Fatigue Syndrome" pre-October 8th 09 was done very differently, and with very different metrics from what one might use now, with the possibility of the potentially profound XMRV/XAND/ME/CFS link.

And consider what many virologists have noted: if you provide therapeutics to patients with ME/CFS and find a reduction/elimination of the XMRV virus and its effects, then that is reverse (but compelling) evidence that the virus does in fact "cause" ME/CFS. The old Ampligen clinical studies didn't do that. And causality is the million-dollar question that we're dying to have answered. The "old" clinical studies of Ampligen in other words - by their unavoidable past exclusion of XMRV metrics to measure efficacy - would not have been as powerful as a repeat clinical study including XMRV pre/post metrics. So this FDA rejection might turn out to be a good thing for ME/CFS patients, and even for an Ampligen manufacturer.

I'm not trying to be a Pollyanna here - and no, I'm not affiliated in any way with Hemispherx - but I can't help thinking that this FDA rejection might turn out to be good for the ME/CFS community. IF whoever owns the Ampligen patent (and that may or not end up to be Hemispherx) moves quickly to directly and credibly measure the effect of Ampligen on Canadian-criteria patients with ME/CFS. Yes, other ME/CFS subgroups, fibromyalgia, MS, prostate ca, might conceivably be included. But if I'm not mistaken what rigorous scientists are waiting for - before they get really excited about XMRV/ME/CFS - are clinical studies that closely match the criteria used by the Science researchers. So a re-do of clinical studies for Ampligen might help get rid of the ambiguity inherent in a fuzzy definition of ME/CFS patients. Get rid of that noise, eh?

Given what we are learning about XMRV and its link with ME/CFS, a rigorous, credible, and relevant evaluation of any therapeutic's efficacy for patients with ME/CFS diagnosed by Canadian Diagnostic Criteria would HAVE to include measurement of the drug's effect on specific tests for XMRV. Unless of course XMRV proves to have nothing to do with ME/CFS - tho I highly doubt that.

I don't dispute Hemispherx's dismal history - nor disturbing reports of safety considerations. So the safety studies should not be dismissed as trivial. However I suspect I'm not alone in remaining keenly interested in the progress of any and all evidence-based research on therapeutics for those of us stuck in the maw of ME/CFS. Particularly clinical studies that directly measure any therapeutic intervention's effect on XMRV titres, byproducts (eg. proteins), and of course clinical symptoms (eg. a la Canadian ME/CFS criteria).

FYI you can hear - from the horse's mouth - about Hemispherx's proposed plans (assuming they stay solvent) in a podcast tomorrow (Thursday).
From: http://www.hemispherx.net/content/investor/default.asp?goto=659
Hemispherx Biopharma Announces Investor Conference Call

Philadelphia, PA, Wednesday, December 02, 2009: Hemispherx Biopharma, Inc. (NYSE Amex: HEB) announces an investor update by teleconference on Thursday, December 3, 2009 at 10:00am EST. The update will cover regulatory status of its platform technology (Ampligen, Alferon-N, Alferon LDO), strategic partnering and other matters, followed by a Q and A period.

To access the conference call:
U.S. Callers: 800-348-5860
International Callers: 973-528-0008
Conference Entry Code: 27781

This call will be webcast via the Companys website at: http://www.hemispherx.net.

A digital replay of the call will be available until December 18th by calling:
U.S. Callers: 800-332-6854
International Callers: 973-528-0005
Conference Entry Code: 27781

 

[dannybex]

Devil's advocate...

...is a good thing!

It's just my understanding, from reading about it months ago, like back in August(?), that the "revised" study results showed back then that there was no statistical difference between the patients and controls, and that's why some are suggesting they knew six months ago that it wouldn't be approved, but kept up a charade in order to keep the stock price up.

But that's just my foggy brained recollection. It could all be a dream.

Or a nightmare...

 

[JayS]

I read something (I think it was by KDM) saying why Ampligen makes some people better and others much worse.

Some PWCs have high protein kinase - usually the ones with very high levels of bacterial infection in the intestine and other places. They have worse gut symptoms than brain symptoms.

Others have low protein kinase (and a different profile of various other immune system markers) and these ones have worse cognitive symptoms and high viral titers.

The second group of people benefit from Ampligen because it raises protein kinase whereas the "bacterial" patients experience worsening of symptoms on it.

I cannot find the original article about this but I think it is interesting and I wonder if anyone else has read anything along these lines?

After reading parvofighter's post I came back to this & unless I'm getting something very wrong this looks like it makes more sense?

 

[Cort]

Hemispherx's response to the FDA decision


To: The CFS Patients, Advocacy Community and Healthcare Practitioners

From: Dr. David Strayer
Medical Director of Hemispherx Biopharma

Re: FDA Response on Ampligen

Hemispherx has received a complete response from the FDA in which the FDA requires one additional clinical study to show a convincing effect of Ampligen in the treatment of CFS and confirm the safety in the target population. The on-going open-label study (AMP 511) and the patients enrolled will continue under the current protocol.

The FDA has provided Hemispherx with a clearly articulated set of recommendations to go forward. I would like to share with you the process we plan to go through with the agency in order to identify the most expeditious path to satisfy the requirements for the approval of the Ampligen NDA.

We plan to schedule a meeting with the agency as quickly as possible in order to obtain additional guidance and clarification concerning a number of matters, including the design of this clinical trial. This will be an ongoing process with the agency.

As part of this dialogue, we plan to evaluate the utility of a special protocol assessment from the agency in order to clearly delineate the clinical trial end points, the statistical methods to be utilized, and to obtain agreement with the agency on the results necessary for approval.

Four factors will support the sufficient execution of this clinical trial. First, the CDC's awareness program has increased public knowledge of the disease. Second, the recent identification of a potential etiologic agent, namely a novel retrovirus, should help accelerate patient identification.

Third, the company plans to utilize longstanding relationships with a group of internationally renowned clinical investigators to accelerate patient enrollment.

Lastly, the company plans to expand recently entered contractual relationships with two of the largest clinical research organizations in the world to accelerate its clinical monitoring and data collection capacity.

Finally, the company has adequate finances and resources to address and respond to all of these FDA recommendations. We have been and will continue to be committed to those suffering from Chronic Fatigue Syndrome. Additional information can be found at www.hemispherx.net. (12/17/09)[/QUOTE]

 

[fresh_eyes]

Very interesting Cort, thanks for posting.

 

[leelaplay]

Press Release - Hemispherx Biopharma Addresses Ampligen(R) Manufacturing Issues

This was submitted by kelly to co-cure today, dec 23 09

I particularly like Kelly's comments regarding the use of the word enigmatic, and the list of other known organic diseases for which there is yet no biomarkers and/or objective tests.

It should be noted that the term enigmatic means hard to understand or
explain - CFS is actually neither. "We know in part" pretty much describes
all of medicine, but it doesn't automatically make it enigmatic.

Although the research water is muddied by the partially successful
career-long attempts by psychiatric liasons Simon Wessely and Peter Denton
White to use CFS and other similar organic diseases to illustrate the
principles of psychiatrist George Engel's biopsychosocial theory, the
biomedical evidence is no more enigmatic than that of other organic
diseases.

Biomedical researchers have no biomarkers and/or objective tests for
Alzheimer's Disease, Huntington's Disease, diabetes or Parkinson's Disease
for example, but no one uses the term enigmatic or enigma to describe them.
Nor is the etiology of many organic diseases known including that of most of
the diseases listed above, but once again, no one uses the term enigma or
enigmatic to describe any of them.

PHILADELPHIA, Dec. 16, 2009 (GLOBE NEWSWIRE) -- Hemispherx Biopharma, Inc.
(NYSE Amex:HEB) (the "Company"), stated that on December 11, 2009, the
Company, via its manufacturing subcontractor, in Spokane, WA, submitted
comprehensive new data to the regional office of the Food and Drug
Administration ("FDA"), Seattle, WA, which Hemispherx management believes
demonstrate that certain manufacturing issues noted in earlier pre-approval
inspections at the facility have been fully addressed. The referenced
reports on Ampligen(R) (Poly I: Poly C12U), an experimental therapeutic
being developed for potential treatment of Chronic Fatigue Syndrome ("CFS"),
are the combined work-product of the staffs at Hemispherx and its
subcontractor. These are the same manufacturing issues sited in previous
10-Q's and the recent 10-K. These manufacturing issues were also part of a
Complete Response Letter from the FDA described in a December 1, 2009 press
release.

About Hemispherx Biopharma

Chronic Fatigue Syndrome is an enigmatic, profoundly debilitating and
potentially life-threatening disease with which a new retrovirus was
recently associated. Researchers are investigating the possible role of this
virus in the symptomatology of the disease using Ampligen(R) as an
investigational therapeutic.

Hemispherx Biopharma, Inc. is an advanced specialty pharmaceutical company
engaged in the manufacture and clinical development of new drug entities for
treatment of seriously debilitating disorders. Hemispherx's flagship
products include Alferon N Injection(R) (FDA approved for a category of
sexually transmitted diseases) and the experimental therapeutics Ampligen(R)
Oragens(R), and Alferon LDO. Ampligen(R) and Oragens(R) represent
experimental RNA nucleic acids being developed for globally important
debilitating diseases and disorders of the immune system. Hemispherx's
platform technology includes large and small agent components for potential
treatment of various severely debilitating and life threatening diseases.
Hemispherx has in excess of 50 patents comprising its core intellectual
property estate and a fully commercialized product (Alferon N Injection(R)).
The Company wholly owns and exclusively operates a GMP certified
manufacturing facility in the United States for commercial products. For
more information please visit
www.hemispherx.net<http://www.globenewswire.com/newsroom/ctr?d=180474&l=4&a=www.hemispherx.net&u=http%3A%2F%2Fwww.hemispherx.net>.


Information contained in this news release other than historical
information, should be considered forward-looking and is subject to various
risk factors and uncertainties. For instance, the completion of the NDA
filing process with Ampligen(R) and the receipt of a Complete Response
Letter from the FDA do not imply that the Company will be able to
successfully comply with any or all of the requirements requested in that
Letter or that the product will ever be approved for commercial sale. In
addition, the strategies and operations of Hemispherx involve risk of
competition, changing market conditions, change in laws and regulations
affecting these industries and numerous other factors discussed in this
release and in the Company's filings with the Securities and Exchange
Commission. Any specifically referenced investigational drugs and associated
technologies of the Company (including Ampligen(R), Alferon(R) LDO and
Oragens(R)) are experimental in nature and as such are not designated safe
and effective by a regulatory authority for general use and are legally
available only through clinical trials with the referenced disorders. The
forward-looking statements represent the Company's judgment as of the date
of this release. The Company disclaims, however, any intent or obligation to
update these forward-looking statements. Clinical trials for other potential
indications of the approved biologic Alferon N Injection(R) do not imply
that the product will ever be specifically approved commercially for these
other treatment indications; Similarly, the completion of NDA filing process
with Ampligen(R) does not imply that the product will ever be approved
commercially.