Dec 20th: High Noon for Ampligen! FDA Advisory Committee Decides Ampligens fate in live webcast

[Nielk]

1) People should not assume that the data that is availabel publicly is ALL the data that is available. FDA can request data from the drug companies but by business laws concerning confidentiality/ patents/ etc., neither FDA nor drug companies are required to release all information to the public. There have been some big scandals in recent years with drug companies witholding data on adverse effects, the drug being approved, and lots of patients being harmed. Some drugs have been pulled off the market or had a big warning label slapped on them because of this.

As a healthcare professional, I used to get mailings almost every week from pharma about new side effects, indications, warnings, etc. These were from drug companies and required by FDA when something new came up.

2) One thought is Hemispherix could have looked at who responded to Ampligen and then work backwards to see what, if any, of their blood tests were different from the people who did not respond. I believe they did a fair amount of bloodwork to screen who qualified for the drug initially and to rule out other causes of disease.

3) An Immunovir study would likely be much les expensive than an Ampligen study. partly because the drug is orally taken, doesn't need a lot of safety monitoring (decades long good safety profile), and is not overly expensive ($100/ month US currently vs. $2,000 or more for Ampligen, not counting infusion cost).

As far as #2, I would think that Hemispherx who have had so much at stake, would have done this. My only thought is that they could not find any definitive markers to identify the responders.

 

[heapsreal]

I think they also need to push approval of antivirals for cfs/me, they have a good idea on how to subgroup these patients. They are already indicated for other illnesses just need to add cfs/me with high viral titres etc.

These are the things that could stimulate more research into cfs/me. Maybe then big pharma might put more money into ampligen, we just need a spark to get things going?

 

[AFCFS]

i think this shows we need more research into diagnoses, biomarkers and sub groups. then they could more easily diagnose us and put us in the right sub group to treat and have a way of monitoring how we are improving, not just patiets saying they feel better or worse??

Agreed. I hate to be a wet blanket, but I just see too much the attempts at political maneuvering and a grab at cash. The disease and people seem secondary, and likely exploited. This is not any different than Big Pharma would do, I think in this case with a Little Pharma it was just more exposed. If it were Eli Lilly, it would probably be available in sample packs by now.

 

[Hope123]

As far as #2, I would think that Hemispherx who have had so much at stake, would have done this. My only thought is that they could not find any definitive markers to identify the responders.

Possible, but never assume and we may never know what actually happened. Sometimes the simplest things and idea get lost in the shuffle. Also, from a drug company point of view, the more people they can get the drug approved for (rather than a subgroup), the more $$$ they can make. Drug companies play an important role in medicine but I never underestimate either the depths to which they are willing to go to earn $$$.

 

[Sasha]

I don't think it's the job of the FDA or their advisory panels to adjust their need for more evidence to fit the sponsor's ability to pay for producing that evidence.

Under normal circumstances I'd agree with that and that would be the FDA's remit but my understanding was that they would apply less stringent criteria (particularly on efficacy rather than safety) in the case of a serious disease with such spectacular unmet need. I thought the whole point of this 'orphan disease' category was to be realistic about a situation in which a disease has received so little funding that there isn't as much good-quality info to go on and patients are so desperately sick that it should be their choice whether to take a drug.

Given that the FDA have, over the years, shown themselves so unhappy with the data provided by Hemispherx, I was disappointed that they wouldn't accept evidence from clinicians who've been using Ampligen. RCTs are only important for showing efficacy [as opposed to effect size or other variables] when a clinical effect is too small to detect otherwise and if clinicians have been successful in identifying responsive subgroups and seeing rapid restoration to health of previously very sick, long-term patients in large proportions of those that they treat, that's data that should be taken into account.

 

[Firestormm]

According to some reports in the financial press, Hemispherx misrepresented the likelihood of Ampligen getting approved in this review, by not disclosing to investors and the public back in June that the FDA had allowed the review based on re-analysis of previous studies, but only while cautioning that "It would be unusual for this type of data to provide adequate evidence of efficacy." The full language of the FDA's message apparently wasn't disclosed until this week's release of background information, and before that HEB was supposedly over-hyping the possibility of approval.

Just catching up this morning. You got any links to the news stories Urban? Commentary is a bit light on the ground and I'm not paying for WSJ subscription

This would perhaps explain the reaction from the market to the review published earlier this week at least in part. That review was not well received - and back in the Summer - when the price was rising on the hype - Hemispherex were selling their own stock (if memory serves). We were talking about it then. Didn't look good for a company who were saying how confident they were.

Edit: Did you mean the Street article posted prior to the meeting, perchance? Looks like you might.

"Hemispherx issued a press release on July 11, claiming the company and FDA "reached an agreement" on new filing requirements for Ampligen. Hemispherx shares were valued at 34 cents on July 11, rising to a high of 89 cents in late September -- a 161% increase. During this period, Hemispherx sold 10.7 million shares of stock through an "At The Market" equity financing facility, netting $9.3 million.

It's hard to imagine a scenario under which Hemispherx's stock would have almost tripled in value and $9 million could have been raised from investors had the company disclosed publicly the FDA's warning that Ampligen data submitted wasn't likely sufficient to get the drug approved.

Hemispherx deceived investors and the SEC, then raised money on this lie of omission.

On Tuesday, Hemispherx shares plunged 32% to 43 cents per share as the truth about Ampligen was finally told.."

 

[heapsreal]

if amp doesnt get approved does that mean that people wont have access to it under current arrangements, whatever that expensive arrangement is called??

 

[Firestormm]

if amp doesnt get approved does that mean that people wont have access to it under current arrangements, whatever that expensive arrangement is called??

Well they were prior to this meeting Heaps. So unless the FDA remove it's experimental/testing status from Ampligen, I can't see why not. Not that I know very much of course.

 

[Firestormm]

Medpage: 20 December 2012: FDA Panel Nixes Hemispherex CFS Drug: http://www.medpagetoday.com/PrimaryCare/SleepDisorders/36569

...Rintatolimod only met its primary endpoint in a confirmatory study after a post-hoc analysis of patients who had CFS for less than 10 years. Excluding 37 patients from the 234-patient trial significantly improved patient outcomes in exercise tolerance testing but also caused the P-value to slip outside the range showing clinical significance.

Members of the agency's Arthritis Advisory Committee voiced confidence that rintatolimod may work in a small group of CFS patients, but that wasn't shown clearly by its manufacturer, Philadelphia-based Hemispherx...

...Panel members were heavily swayed by nearly 2 hours of compelling patient testimony from patients during the meeting's public hearing portion. Even panelists who voted no said they didn't want to keep the drug from patients who might be helped, although it might be just a small group...

The FDA's analysis also found discrepancies in the drug's safety data -- so much so that FDA officials called what Hemispherx submitted unreliable.

"As we reviewed the sponsor's data, we found multiple areas of discrepancies," Michele said. "Every time, we see that it raises our eyebrows a little bit and makes us question whatever else is in the packet."...

 

[Firestormm]

Wall Street Journal. Full article kindly reproduced: http://www.mecfsforums.com/index.php/topic,14500.0/topicseen.html

The FDA and the company differed on whether one of the main clinical studies reached a goal showing a statistically significant test showing patients receiving the drug were able to walk on a treadmill for a longer period than patients receiving placebo injections.

The company said on average there was an improvement of about one minute while the FDA said the difference appeared to be about 20 seconds.

Thanks Wildaisy

 

[a2mandel]

That part is a bit hard to understand for me too. It's evident that the FDA has made a serious new commitment to ME/CFS in this past year, and that they've allowed Ampligen to advance to the point of having an advisory panel review, which is farther than it's ever gotten before. Maybe they wanted to show due diligence in allowing Ampligen an open hearing by the independent experts, even if they kinda suspected what the outcome was going to be. If nothing else, this hearing aired the important issues for the pharma community - the FDA is expressing that they DO feel a sense of urgency about the need to find treatments, and would welcome other sponsors to come forward - Unger said this at the end, in so many words.

I feel the same way. I am an ampligen patient and the impression all of us had at the site where we infuse (both staff and patients) was that the FDA had agreed that the older data was sufficient

 

[Firestormm]

I feel the same way. I am an ampligen patient and the impression all of us had at the site where we infuse (both staff and patients) was that the FDA had agreed that the older data was sufficient

Hi Amandel,

I might be wrong here, but I don't think we heard from the FDA prior to their briefing document published on Tuesday ahead of the meeting; indeed the only positive noises we really heard were from the company and positive analysts.

It might be that the FDA meeting in February will scale-back their previous demands for a new Trial. It might be that the Advisory committee positives will mean that Ampligen is not taken off the board. I don't think this marks the end. I think HEB will have to look for 'sponsors'/partners and be prepared to open-up and share any future financial benefits.

That said, they raised $9million in the Summer from sales of their own shares. Quite whether this means they now have a better balance sheet I couldn't possibly say - but HEB have not (yet) said if they are now able to complete a Trial as was previously requested. Maybe they will be able to with this extra cash.

Rehashing/interpreting old data is not wrong (apparently). What might be considered wrong is the inference in that article above from The Street that HEB knew the FDA were not as happy with things as they led people to believe (or they did not seek to correct the impression of investors and benefitted financially from it). If there is an investigation (I doubt there will be) this could also have an effect.

It will be interesting (vital) to hear from HEB about what their future plans will be now. Should get more comment later today when America properly wakes up I guess.

 

[Nielk]

The FDA's final decision has not come down yet. They have till February to decide. They take this decision from the panel into account but, they make their own decision. I have been speaking to someone who is knowledgeable about the FDA procedures and it seems that there are rare occasions when the FDA goes against the advisory panel's decision. Especially when the vote is pretty close. They also look at who voted in what way.
I don't believe that this will be the case with Ampligen. I think that it's pretty clear that the FDA is not ready to approve it but, it is not over till the fat lady sings...

 

[Firestormm]

"The FDA does not have to follow the recommendations of its advisers but briefing documents released by the agency strongly suggest that it will.

The FDA’s list of deficiencies in the drug application submitted by Hemispherx Biopharma is stunning and encompasses nearly every aspect of clinical testing.

“Key deficiencies included inadequate evidence of effectiveness or safety, inadequacy of drug-drug interaction studies, lack of carcinogenicity assessment, lack of anti-drug antibody determination, and inadequate analytical methods and drug product specifications,” the agency wrote in one of several sections listing problems associated with the application.

FDA representatives also expressed concern over inconsistencies in the data and statistical analyses. An agency representative says of the data: “It raises our eyebrows and makes us wonder what else is in the database that we’re not seeing.”

http://blogs.nature.com/news/2012/12/panel-rejects-experimental-chronic-fatigue-syndrome-drug.html

 

[Valentijn]

Did they show the final tally of votes? How many for and against?

 

[Firestormm]

Did they show the final tally of votes? How many for and against?

WSJ said 8 to 5 against, and Nature above - said 9 to 4 against. Go figure! Maybe different votes? I don't know.

 

[xchocoholic]

Sorry, I haven't been following this but I have a couple of questions. So far all I've heard is that they don't know why
Ampligen helps.

Can you tell me if any of the markers discussed as prevalent in cfs by
the people who gave these lectures to the fda were tested for by the manufacturers of Ampligen ?

If so, which markers were positively affected by ampligen ? Which markers were negatively affected ?

And what marker are used to determine who will benefit from ampligen ?

And can they explain why these markers were altered by ampligen ?

Tx .. X

 

[justinreilly]

If I understand this right, HEB re analyzed the data from its two placebo controlled studdies. They took out everyone who was sick over ten years and on this group, under 10 yrs, the drug was effective but the p value was 0.10 which is deemed not statistically significant, bc it's over 0.5.

But then there are questions about safety that I wasn't aware of until recently. There is a piece on the NCF site by a patient who says she was in a trial and she and several others dropped out bc of adverse effects, but that they weren't counted as having adverse effects, just shown as being dropouts. The patients says she is still worse than when she started Ampligen 10 years ago.

Before I took Ampligen I read everything about it available to me and spoke with as many previous patients and physicians as I could. I discovered far more negative experiences than positive ones, but I persevered because I thought that I could not get any sicker believing that, at worst, the stuff would have no effect. Many others felt the same way. But I was wrong. We were wrong. Some were dead wrong. I imagine patients currently pursuing Ampligen likely harbor the same combination of hope and desperation that I did. I hope they consider the following:

Ampligen is some sort of extremely potent drug — no placebo, no homeopathic, no question. I became exceptionally ill during the first week of the 24-week infusion regimen, and many other subjects did equally poorly. I suffered less severe but still extreme reactions on every infusion day for the subsequent months, and many others had the same experience. I was told by the physician administering Ampligen to our group of patients — and he was told by Hem's medical director, the only person who has ever been Hem's medical director (b/c carter has dirt on him from Sprayer's research when they were in med school together) — that such side effects were actually encouraging and indicative of a positive final outcome. It was not until week 22 that I was told by 2 separate Heb employees that in candidates for whom pain is a prominent symptom that Ampligen should always be avoided as it is likely to exacerbate pain. Often permanently! Which it did. At the end of my therapy, I was considerably sicker than I ever had been before Ampligen; many other patients had the same experience. Thirteen years have passed, and I remain sicker than I was before Ampligen, right through today. My experience is far from uncommon.

http://www.ncf-net.org/forum/2011fall2.htm

She also talks about HEB threatening to sue CAA if it continued to survey patients who took Ampligen. CAA destroyed the survey documents. This sounds shady to me on the part of HEB.

Here's another article from the NCF newsletter with quoted letters from a couple of other patients saying similar things about safety.

http://www.ncf-net.org/forum/ampligeninPink.htm

The FDA briefing paper and some of the comments of the committee members indicated that HEB hadn't shown safety and had failed to disclose and factor in some instances of adverse events.

If HEB hasn't really shown safety, then I am less enthusiastic about Ampligen, especially for myself having been sick for 11 years.

what do you guys think about the safety issue?

 

[Nielk]

I think that the fact that Ampligen could do irreparable damage is very alarming, if true.

 

[john66]

I just want to weigh in here from the perspective of the job I used to have selling packaging to the pharma industry. It seemed like a lot of the drugs for AIDS were fast tracked, and lots of the normal and routine data were not given as close scrutiny as other drugs for other diseases. In my local CFS group, we have touched on this. I was hoping this would get approved, not only for helping people, but for putting CFS/ME on the map such as Fibromyalgia drugs like Lyrica did. I'm sure all of this has been said, but I can not help but feel an overwhelming sense of disappointment.