CFSAC Comments August 2015: Ampligen Price Increase on Shaky Ground

I looked into the Ampligen issue–the exorbitant 267% price increase by Hemispherx–some more. Here is one thing that patients who are currently enrolled in the trial can do. They can contact Schulman Associates, the Institutional Review Board (IRB) for this trial at: Schulman Associates Institutional Review Board, Inc., 4445 Lake Forest Drive, Suite 300, Cincinnati, Ohio, fax: 866.377.3359. The IRB was “established to help protect the rights of research subjects” and encourages trial participants to write to the IRB “[i]f [they] have any questions about [their] rights as a research subject, and/or concerns or complaints regarding this research study….”

I also sent a follow-up message to FDA’s Dr. Woodcock with additional information regarding the distressing new price for Ampligen. I submitted that message together with my message to Dr. Woodcock from two days ago as official comments for the CFSAC meeting next week urging CFSAC, especially its FDA ex officios, to follow up with Dr. Woodcok. My CFSAC comments are reproduced below. (My new message to Dr. Woodcock starts under “August 13, 2015 Letter.”)

CFSAC Meeting August 18th-19th, 2015

Public Comments by Jeannette Burmeister

Submitted on August 13, 2015

I would like to urge CFSAC, particularly its FDA ex officio members, Drs. Maynard and Hall, to follow up with Dr. Woodcock regarding Hemispherx’s enormous price increase for Ampligen. Since FDA has regulatory authority over cost-recovery programs such as the Ampligen trial, I am asking that FDA exercise its authority to audit the justification of the new price and to re-assess its authorization of the increased price.

Below are two letters I sent to Dr. Woodcock on August 11, 2015 and today (August 13, 2015) with more details about the situation, which is dire and urgent.

August 11, 2015 Letter:

You can read my August 11 letter at 267% Price Increase for Ampligen.

August 13, 2015 Letter:

Dear Dr. Woodcock,

As a follow-up to my letter of August 11, 2015 regarding the enormous price increase for Ampligen by Hemispherx Biopharma, Inc. (“HEB”), I wish to raise a few additional issues.

As you know, FDA may allow drug companies to recover certain costs for investigational drugs in accordance with 21 C.F.R. 312.8, as it has done in the case of HEB and Ampligen. In order for a drug manufacturer, a so-called sponsor, to charge for certain costs for a drug undergoing clinical investigation, certain requirements have to be met.

In accordance with 21 C.F.R. 321.8(d)(1), a sponsor may recover only the direct costs of making its investigational drug available, not the indirect costs. The regulations further provide:

“Direct costs are costs incurred by a sponsor that can be specifically and exclusively attributed to providing the drug for the investigational use for which FDA has authorized cost recovery.“

“Indirect costs include costs incurred primarily to produce the drug for commercial sale (e.g., costs for facilities and equipment used to manufacture the supply of investigational drug, but that are primarily intended to produce large quantities of drug for eventual commercial sale) and research and development, administrative, labor, or others costs that would be incurred even if the clinical trial or treatment use for which charging is authorized did not occur.”

In March of this year, Hemispherx announced the completion of an $8 million facility-enhancement project in New Brunswick, N.J. to allow for a higher-capacity manufacturing process for both Ampligen and the company’s other drug, Alferon N. In the same month, HEB announced plans to commence distribution of Ampligen in Australia and New Zealand. This week, HEB announced that it was getting ready to supply Ampligen to patients in Europe and Turkey. As Australia, New Zealand, Europe and Turkey are currently completely untapped markets for Ampligen, it seems likely that the upgrades to the New Brunswick facility were made in anticipation of commercially selling the drug in these large new distribution areas, especially given the timing; the completion of the enhanced facility nearly coincided with the announcement regarding Australia and New Zealand and was followed, only a few months later, by the announcement with respect to Europe and Turkey. HEB will need to produce Ampligen in much larger quantities now in order to satisfy the demand in the new markets and with its upgraded facility will have the capacity to do so. In addition, HEB, by its own admission, is still actively and diligently pursuing FDA approval in the U.S. If it is successful with that endeavor, the new facility will be used to produce large quantities of Ampligen for commercial sale in the U.S. Consequently, the facility-enhancement project is likely an indirect cost and not recoverable under FDA regulations. Therefore, should HEB have included it in the cost justification for the price increase in the U.S. market, that would constitute an improper cost calculation and, given the magnitude of the project, even if depreciated or amortized, it alone may account for the Ampligen price increase.

Moreover, HEB has incurred manufacturing costs for the study of Ampligen treatment of other indications, e.g., Ebola, HPV, HIV, hepatitis and influenza. Were the costs for those efforts included in the cost justification for the open-label-trial price increase?

I also want to make you aware of the fact that the documentation that patients had to sign in order to enter the trial makes the express representation that the charge for the drug is “expected to be $2,100 for the first eight (8) weeks and $2,400 for each additional eight (8) week period.” Obviously, modest, justifiable price increases are to be expected and not objectionable. Dramatic increases—certainly those in the ballpark of 267% (an increase of $26,000 per year, from $15,600 to $41,600)—are not; they are inconsistent with the terms on which patients agreed to participate in the trial. In an FDA-regulated trial, such seeming price gouging ought to be impermissible, especially given the concerns as to the cost calculation and the representations made to the participants in the trial, many, if not most, of whom have made substantial personal sacrifices, financial and other, to participate and have also, over all these years made contributions, often at a price to their health, to HEB’s FDA-approval efforts for Ampligen by frequently completing extensive paperwork, undergoing large blood draws, performing stress tests twice a year, traveling to D.C. to testify in support of the approval of the drug, etc.

These and potentially other concerns raise serious questions as to whether the tremendous price increase for Ampligen was implemented properly and is otherwise permissible. Since FDA has regulatory authority over cost-recovery programs such as this one, I am asking again that FDA exercise its authority to audit the justification of the new price and to re-assess its authorization of the increased price. I do not purport to speak for anybody other than myself, but please be aware that the situation is a top priority for many in the patient population.

Sincerely,

Jeannette Burmeister

cc:

Dr. Stephen Ostroff, FDA Acting Commissioner (via email)

Nancy McGrory, Hemispherx Patient Advocate (via email)

Schulman Associates Institutional Review Boards (via fax)

This entry was posted in Uncategorized and tagged , , , , , , , , , , , , , . Bookmark the permalink.

42 Responses to CFSAC Comments August 2015: Ampligen Price Increase on Shaky Ground

  1. Laurel says:

    Wow. Thanks so much for doing this, Jeannette.

  2. Liz Willow says:

    Brilliant! I thought HEB must be violating some federal regulation. And then there is the contract issue — the agreement all Ampligen recipients had to sign. I sincerely hope participants in the open-label Ampligen trial contact the IRB as you suggest in your first paragraph. I will be watching to see if the FDA does its job.

    • Thank you, Liz!

      Given the company’s history, my sense, too, was that checking it out more thoroughly might reveal something. FDA needs to step in here and then fast track the drug, so that everybody who wishes to try it has access to it.

      • Kelly says:

        I agree with Meghan below. Hemispherx is an unethical company run by people who pay themselves millions each year, while the company tanks. I don’t think they give a damn about patients. From wikipedia:

        “In December 2009 the FDA issued a CRL refusing Hemispherx’s new drug application for rintatolimod’s treatment of CFS. The FDA concluded that the two RCTs “did not provide credible evidence of efficacy.” The agency recommended a minimum of one additional six month 300 patient study, and rodent carcinogenicity studies.”

        It’s been six years. Why haven’t they started the 300 patient study?

        • Meghan says:

          Several studies need to be done. 1) study those few on ampligen find out what it is working on since the drug acts like poison to many more.

          2) offer education to those doctors who will administer it.

          3) meet the FDA requirements of a drug. Then maybe the drug can be accepted in UK, EUROPE, AUSTRALIA JAPAN, and other countries that have stricter regulations on drugs

          Sent from my iPad

          >

          • I have now seen a fair amount of ppl on the drug and it really is fairly well tolerated by most. In fact, I have not seen anybody who had to quit due to toxicity. I have seen a good number of ppl who have had to stop other drugs because they were too toxic, particularly straight-up antivirals.

            Ampligen is not the only drug whose working mechanism isn’t understood. SSRIs, e.g. We don’t know how they work, yet they are approved. Although it’s, of course, always preferable if that is known.

            I think the physicians currently administering it have a pretty good idea who it will work for. Dr. Peterson has something like a 70 or 80% success rate. But there definitely is a learning curve for physicians.

            A new well-designed placebo-controlled study would clear up a lot, but that doesn’t seem in the cards. $2.75 settlements plus legal fees will do that. So will unreasonable salaries and bonuses in the millions for the top executives that are being paid despite the dire financial situation of the company. Etc.

            It’s really a shame because it’s a drug with a lot of promise for certain patients and I think it’s good to keep that in mind. But seriously, many of us has have been nothing but supportive of HEB in so many ways despite them being vulnerable on several fronts and this is how we are being repaid? Sucker punched doesn’t begin to describe it.

              • Meghan Shannon says:

                I know of four people personally that Mary Schweitzer knows who had severe reactions. All under Either Dr. Peterson or Enlanders care.

                Indeed is right

                • Not doing well is not the same thing as a “major toxicity.” A major toxicity is what happens when I take Vistide – my liver markers skyrocket. A major toxicity is what happened to some of the patients Steve Straus put on IV Gancyclovir back when he was still saying it was chronic EBV (but neglected to hydrate them properly) – at least one lost a kidney. Those are major toxicities. There are people who seem to have the right biomarkers, but the drug does not help them, and quite often they have pain problems while on it. One patient I know quit taking the medicine she had been on for years so she could take Ampligen, but it turned out the medicine she had been on worked better for them than Ampligen did, and so she got sicker. Finally, having to move or commute long distances to an infusion site can completely negate the positive effect of the drug – and if the drug isn’t helping you, it can really make you worse. These are not reasons to deny PROVISIONAL acceptance of the drug.

                  • I second what Mary said. Thanks, Mary!

                  • Meghan Shannon says:

                    Mary , I did say toxic reaction to ampligen . I do know people as I said who had toxic reaction. One in particular was in and out of E.R.

                    And I agree that those few who are on this drug and it works for them should stay on this drug.
                    Hemispheric pharmaceutical company is completely out of line.
                    Meghan

  3. Meghan Shannon says:

    Hemisphrex isn’t even approved by FDA for AMPLIGEN FOR PEOPLE DIAGNOSED WITH CFS much less ME.

    PEOPLE ON THIS DRUG NEED TO BE PROTECTED NOW.

    This pharmaceutical company isn’t ethical.

  4. Sharon says:

    Thank you, Jeanette – beautifully expressed as always.

  5. joey tuan says:

    Thank you so much Jeannette!

  6. As I sit here staring at the new contract I am supposed to sign, I have to congratulate you, Jeannette, on two brilliant letters. I will try to write one.

  7. Ess-OriG says:

    Thank you, Jeannette, for speaking up–this will mean a lot also to future patients with the potential of Ampligen use.

  8. libbyboone says:

    Thanks Jeannette. This will ultimately help many people, I hope.

  9. John Gabor says:

    Excellent letters Jeannette

  10. kmdenmark says:

    Thank you for your activism, Jeanette!

  11. Deborah Waroff says:

    Fabulous work. No way are they going to get the proposed prices out of Turkey or any European country. This price rise on a captive and vulnerable population amounts to racketeering. I’d like to see a prosecution. Meanwhile, I believe HEM should be taken over by eminent domain and its patents reassigned to a non-profit entity capable of finishing the trials, such as Stanford.

  12. Nancy says:

    Jeannette, you’re awesome. Thank you for all the work you do, and the ENERGY you spend in your advocacy for patients. I haven’t signed either.

  13. Quoting from Lexis/Nexis:

    “Hemispherx Can’t Duck Suit Over $2.1M Exec Bonuses

    A Delaware Chancery judge on Tuesday refused to throw out a shareholder suit challenging Hemispherx Biopharma Inc.’s $2.1 million in bonuses for executives who led a doubling of the biotech’s market capitalization, saying too many questions remain.”

    http://www.lexisnexis.com/legalnewsroom/securities/b/newsheadlines/archive/2015/08/18/hemispherx-can-39-t-duck-suit-over-2-1m-exec-bonuses.aspx

    • Doesn’t look like there’ll be much left over for us …

      • Kelly says:

        HI Mary,

        I’m curious if you’ve ever tried anything else besides Ampligen? It seems like a miracle drug for you, but not that much for most others. Plus, quite a few patients are improving by addressing mitochondrial issues, dysbiosis and microbiome issues, methylation, heavy metal and other past environmental exposures, mold, etc..

        The latter is a lot more complex and complicated, but there’s no doubt that some people are getting their lives back, or at the very least, improving slowly but surely.

        Have you tried or are you trying some of these other approaches?

        • I know many others who have improved significantly on Ampligen – I’m just “out”. We have been attacked for saying we are on it, so most patients won’t talk about it on internet.

          My choice of remedy is tied to my biomarkers. In 1998 I was in a study that found me VERY positive for HHV-6A – over 10 times the amount that would be needed for a positive diagnosis – plus I was positive for the 37kDa Rnase-L immune defect. The latter was a good indicator of success with Ampligen, and while Ampligen was not available in the US (most of the 1990s), two researchers had found that Ampligen made HHV-6A go dormant in test tubes. After six months on Ampligen, not only had my symptoms been substantially relieved, but I was also negative for the 37kDa Rnase-L, and HHV-6A had gone dormant.

          Later, when off Ampligen because the head of my practice in Philly died and FDA took the drug away (and there was no place within a 100-mile radius where I could get it), I flew out to Tahoe and Dr. Peterson ran a lot of tests on me. aside from the toxic stew in my blood, he found active HHV-6 and CMV (cytomegalovirus) in my spinal fluid, plus, again, the 37kDa Rnase-L. And my natural killer cell function was 2-3%.

          I have 6 observations of being on and off Ampligen. Off it, I had immune defects and was plagued with re-activated or chronic viral assaults. I had significant symptoms of encephalitis. I had abnormal SPECT scans. I was bedridden and miserable. On it, the immune abnormalities disappeared and the viruses went dormant, while I no longer had severe pain behind my eyes and in the back of my neck (which had been 24/7), I no longer had significant cognitive dysfunction (ataxia, expresive dysphasia, blackouts, absence seizures, partial paralysis, disorientation, almost no short-term memory, and massive confusion) – there comes a day when you actually don’t feel sick, which is amazing if you have spent years with this disease.

          I went from being bedridden to being able to walk barefoot on a beach. I can drive! I can read! Conversely, returning to hell (one year off Ampligen the first time, 7 months off Ampligen the second time) is … well, hell.

          When I was unable to get Ampligen we did try Vistide, which is approved for CMV and Peterson has found works for the combination HHV-6 and CMV – but my liver rejected it, even in very very small doses. I did seem to respond to IM gamma globulin when I got a shot rather by accident (a dishwasher at our favorite restaurant got hepititis and we all had to go get a shot – everybody else was upset but I was psyched, because I was hoping it would help – and it did for a couple of weeks; got me through Christmas.) – but gamma globulin is more expensive than Ampligen.

          Given my biomarkers and symptoms on and off Ampligen, there is no doubt that this drug works for me. If I have mitochondrial issues, for example, they appear to be secondary to the immune/viral combination. That does not mean that other remedies aren’t better for other people – just that this one works very well for me, and for the subset of patients who have the same biomarkers I do.

          For the record, I tend to improve faster than most patients, but I also tend to relapse unusually quickly. Most patients don’t have to stay on the drug like I do. That IS unusual.

  14. Meghan Shannon says:

    I am sorry to hear that you have been attacked for being on ampligen. No one should be attacked for what works for them. I have always heard people want to be on ampligen. Seems weird to hear people attacking those on the most wanted drug in the USA. lol

  15. Meghan Shannon says:

    I don’t believe you. No need to post. I am gone from this

    • Wow! Uncalled for.

      I approved it because I think it’s important that others see this.

      • Kelly says:

        Yes, what an odd response from Meghan. First she says she’s sorry to hear that Mary’s been attacked, then when you basically agreed, she says ” I don’t believe you.” ???

        I hope Meghan wasn’t referring to me. I certainly wasn’t attacking Mary, just asking her if she’d tried other options or protocols that others are using. And I asked mainly because it seems like there could be the possibility that Ampligen may become too pricey to continue, or just never get approved.

        Jeannette, I saw your tweet that Hemispherx had back-dated one of the price increase letters, but didn’t understand the significance of that. If you have a moment, could you explain please?

        • It was an unfortunate and unprovoked comment.

          Re your question, Hemispherx made the price increase effective as of July 24, when it didn’t have IRB approval yet. This is seemingly a violation of 21 CFR section 56.108(a)(4), which provides, “In order to fulfill the requirements of these regulations, each IRB shall: (a) Follow written procedures: … (4) for ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval….” In other words, changes to the protocol must be reviewed and approved by the IRB before they are implemented.

  16. Pingback: 267% Price Increase for Ampligen | Thoughts About M.E.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s