I think it's time to reassess Hemispherix, whose new drug application for Ampligen (their only) drug, was recently accepted for FDA review.I also want to address some of the issues that made Fools skeptical about Hemispherix in the past. Ampligen is primarily intended to treat Chronic Fatigue Syndeom (CFS), so a large portion of the discussion involves background on CFS, trends in relevant research, and the role of the FDA. Hey at the least it all makes an interesting story.Firstly, there are two different camps in CFS research - (a) government research primarily from the CDC (and also NIH) and (b) a strong network of primary care physicians who treat CFS (often with Fibromyalgia) and have transitioned into research. The former primarily investigate the psychological and cognitive aspects of CFS, while the latter have been digging for physical causes. If the total research picture seems inconsistent, it's often due to discrepancies between these 2 camps, which go so far as to use vastly different research definitions of CFS. Nonetheless, if you follow strands from individual groups of researchers who use the same criteria for CFS, then the picture is not quite so hazy.Secondly, many doctors in the physician camp view Ampligen as a solid cure for CFS, which at the least will work wonders in a substantial subset of patients. You can easily find websites and articles by/about these physicians, some top names include Daniel Peterson, Paul Cheney, and David Bell. Among these doctors, Ampligen is not seen as a risky, fringe, or even "experimental" drug. They don't have financial ties to Ampligen, they're simply genuine concerned doctors, who were flung into this mess when people in their town started coming down with CFS. Peterson and Cheney, who were the first physicians to treat CFS in an "outbreak" in the 80's, actually proclaimed that Ampligen was the cure, as far as they were concerned. But there was another twist: The FDA demanded more research.The delay in approving Ampligen (20 years and counting) is due to politics and research surrounding CFS, not to Hemispherix's efforts. When the FDA initially reviewed the drug, many government scientists were still questioning the validity of CFS as a disease, and there was (and still is) bias towards framing it as a psychological illness. In fact, many of the symptoms that the FDA deemed side effects form Ampligen - flu-like symptoms, heart-related symptoms, and occasional elevated liver enzymes, and others - are actually classic symptoms of CFS. CFS is so impairing that other deemed "side-effects" really don't hold a torch to it. However, the FDA deemed that these were side-effects of the drug because of debate over the core physical symptoms of CFS - a decision which cut the last ties between expert CFS physicians and governmental research efforts 20 years ago.As it stands currently, the FDA is still being stingy regarding Ampligen. I recently heard a speech by an FDA spokesperson who said that wee need to find a biomarker for CFS in order to facilitate Ampligen's approval. Once again, though, non-governmental researchers have found many biomarkers when using more solid research definitions of CFS. And moreover, the FDA doesn't require a biomarker for most of their drug-approvals. Nonetheless, pressure has steadily continued to approve Ampligen since it was created; and furthermore they recently approved the first drug for Fibromyalgia (Lyrica), which a disease often seen with CFS, and filled with similar political controversy.Of course, these are all just opinions, but trust me they're shared by many other people as well (see the book Osler's Web for much more detail).However, since they're not mainstream, you won't see them in a typical analysis of Hemispherix.Ampligen will be approved some day, it's just a matter of time - hopefully, by now, it'll be a question of years and not decades.As for the financial strength of Hermispherix - and their ability to profit off their only drug - I was curious about what other Fools have to say.
To cure CFS is to cure the malingering.
There's no evidence to suggest that CFS is malingering.
Hemispherx is run by a fraud.Look into Cypress for what I would prefer to bet on, if I took long positions in biotech very often.(ok, I'm looking at nibbling at IMGN and still love BMRN, and enjoyed the pop from Lev)
CFS is a difficult disease to figure out. I'm sure that this phenotypical presentation of disease comes from something 'organic' but I would be cautious in investing in anything remotely associated with this diagnosis. When a diagnosis is almost impossible to define it is very difficult to prove a therapy actually works for it. I very seriously doubt the cautious FDA would risk approving a drug that would be extremely contraversial at best. Look at what happened to the diagnosis of 'hysteria' from an old DSM. This very common diagnosis seems to have mysteriously disapeared from conventional medical literature. Interesting medical anthropology! Take a look also at post traumatic stress disorder. Another interesting medical diagnosis with a fascinating history. Medical anthropology might not be an obvious source of information to base investement decisions on but it can be surprisingly helpful... Now combine anthropology with phylogenetics!!! That's powerful...JPG PS: Never heard of Hemispherix but sounds like a good short position for a CAPS game...
You raise a good point that CFS can be difficult to pinpoint, but once again, it really depends on the source of information.The CDC (along with agencies in England) use loose non-specific definitions, with criteria such as extreme fatigue, irritability, and depression; patients have to meet something like 4 of 8 symptoms, with each symptom given equal weight. They're most likely studying a heterogeneous set of patients, who probably respond to treatments differently. They’ve also reported that a large portion of their participants work full-time, which is at odds with CFS’ typical clinical presentation.However, clinicians who treat CFS have a distinct clinical picture of the disease, which has been fleshed out with relevant research. Specifically, the fatigue is defined by post-exertional malaise - fatigue following exertion, which is unproportional to the activity. A sizable portion of the fatigue is often attributable to orthostatic intolerance, which is when your blood pressure fails to rise when you stand up. Orthostatic intolerance causes a unique set of symptoms and behaviors, marked by light-headedness upon standing (or even sitting) and compensatory behaviors, such as crossing one's arms or legs and the need to lie down. Another characteristic of CFS is disturbed and unrefreshing sleep. Cognitive dysfunction (or "brain fog") is also one of the most prominent subjective complaints. Taken all together, CFS can still be tricky to define, but the characteristics above are still distinctive and specific to CFS, to the extent that seasoned doctors often just know it when they see it.Complementary research findings include up-regulated nitric oxide, likely causing or caused by vasodilatation, a hypercoagulable state, and numerous immune abnormalities (lowered natural killer activity, increased Rnase L activity), which are often interpreted as evidence for a hyperactive immune system. In line with all this, beneficial treatments include drugs for orthostatic intolerance, NO scavengers, sleep meds, and drugs to improve cognitive function – these categories of drugs can drastically improve functioning, but none of them (alone or in combination) gets rid of all the symptoms. Nonetheless, their benefit is well documented in the literature, so long as you're reading a study with a good definition of CFS (which is likely to most studies not connected to the government). That's all to say that there is a distinct picture of CFS, despite any misconceptions among the public (which partly stem from the ambiguous name CFS).Ampligen is not a mystery drug – it’s not like one of those psychoactives that help somehow but through an unknown mechanism. It’s been around since the 60’s, and it modulates the immune system by down-regulating Rnase L via cells’ toll-like receptors. Initial studies for Ampligen used very strict criteria and recruited only the most impaired patients from the top CFS physicians around the country – a group that typically doesn’t respond at all to any treatment. The results – at least for 2/3rds of the patients – were nothing short of miraculous. Patients who couldn’t get out of bed for years or even a decade started living normal lives without any sign of remission for years, until they could either no longer afford the drug (at $20,000/yr) or it was no longer available; subsequent studies have found similar results with more patients (all combined to make a sample of 700-800 participants). In fact, the majority of pressure for the FDA to approve Ampligen isn't from Hermispherix, it's from CFS advocacy groups, those patients who once regained their lives on Ampligen, and experts in the field, who estimate that it will greatly benefit 2/3rds of their patients, fulling curing around half of them.Returning to the potential of Hermispherix, 2 conclusions to keep in mind.First, the current estimate of the prevalence of CFS, I think it’s 4 million, is generated by poor epidemiological studies by the CDC. Due to their loose criteria, that’s most likely an overestimate. Ampligen will be marketed towards a more select group of patients than CDC estimates would have you believe.However, CFS (defined properly) is a growing disease with a demand for better treatment options. Most doctors know little about CFS, and those who do typically stumble into the field, either from seeing and treating more CFS patients than usual which generates word-of-mouth reputation, or because of the similarities between CFS and their previous specialties. Treating physicians in the field are often swamped with patients; the number is slowly growing, but treating CFS is rarely profitable (due to the amount of attention that needs to be given to each patient and adjusting treatments) and is often looked down upon by high-brow research institutions. But more importantly, CFS physicians know what they’re doing, they know CFS (without harboring vague ideas about it), and they know how Ampligen is believed to help. *Ampligen’s market for CFS, at least at first, will be among these informed physicians and their patients*.
t’s been around since the 60’s, and it modulates the immune system by down-regulating Rnase L via cells’ toll-like receptors. Initial studies for Ampligen used very strict criteria and recruited only the most impaired patients from the top CFS physicians around the country – a group that typically doesn’t respond at all to any treatment>>Been around since the 60's...but never approved.Hence my problem with management. Carter's been running that company as his personal bank account for decades with nothing to show for it, but a bunch of diluted (and deluded?) shareholders.So, to sum:1) poorly-defined disease2) a "treatment" that's been around for (almost) ever with no real clinical record of success3) self-dealing managementsounds like a short to me, but it's only a buck stock so I'll just let it die.David
4 out of 8:1) Impaired memory or concentration2) Postexertional malaise3) Unrefreshing sleep4) Muscle pain5) Multijoint pain without swelling or redness6) Headaches of a new type or severity7) Sore throat that's frequent or recurring8) Tender cervical or axillary lymph nodeswho does not have days where they do not have the first 6??? CFS is the diagnosis you give the crying upper / uppermiddle class person in the corner that says, "but something is WRONG with me! you dont get it!" pick any number of SSRIs, call it a day, and hope they dont come back to the office unless they have good insurance.
Thanks for your insight Fuma102.You might benefit from reading the rest of the post, which describes what's wrong with those criteria.Post-exertional malaise (fatigue + cognitive dysfuntion) that's unproportional to the mount of preceding activity. Orthostatic intolerance. Fatigue that doesn't respond to any amount of sleep. Unremitting flu-like symptoms. And documented immune abnormalities.Those symptoms are not shared by everyone.
>So, to sum:>1) poorly-defined diseaseThe disease is only poorly defined by incompetent researchers. Informed physicians who know their stuff are the ones who are going to be using and purchasing Amplgien.>2) a "treatment" that's been around for (almost) ever with no real >clinical record of successPerhaps it speaks most that Ampligen's main supporters are patients who have been on it and expert doctors who believe that their patients will benefit. (I've met some of them). Delays in approving the drug (which was first used for CFS in the late 80's) have been due to the government's bias towards viewing CFS as a non-real disease. The flip-side of the issue that it's been 20 years and there's still pressure by all the relevant parties (physicians, patients/advocacy, and Hemispherix) to get Ampligen approved. Surely you wouldn't expect that scenario for ineffective drug meant to treat an ill-defined disease.>3) self-dealing managementThis I know less about. I'm still easing into the world of investment, and am eager to learn more about these aspects of business. (As an aside, are there good sources to get the scoop on a business' management, or is just a question of doing the right internet searches?)
I got the criteria straight off the CDC website, but bake it to fit your tastebuds.
You did get it from the CDC website.I'm saying that the CDC's definition is poor and ambiguous, and many others agree. Even you guys were saying that anyone would meet the CDC criteria for CFS. They're lousy criteria. (See for example http://www.cfids-cab.org/MESA/ccpc.html, I'm sure there are many other sites).Ampligen has been studied and used by doctors who know how to define CFS, most or all of whom who have disassociated themselves from the CDC due to years of bitter argument. Ampligen has made it to the FDA's door all in spite of the CDC's lack of support for Ampligen (and studying the immunological mechanisms of the disease) and their meaningless research into CFS. It didn't just stumble in the door.
How far back have you gone in their 10K filings? What about all those other diseases Ampligen was supposed to treat? This thing has been thrown at everything under the sun.
The disease is only poorly defined by incompetent researchers. Informed physicians who know their stuff are the ones who are going to be using and purchasing Amplgien.>>Who are the researchers at the FDA who are going to approve this? Those same incompetent ones. Whoops.>>Perhaps it speaks most that Ampligen's main supporters are patients who have been on it and expert doctors who believe that their patients will benefit. (I've met some of them). >>Two words: Placebo effect.>>Surely you wouldn't expect that scenario for ineffective drug meant to treat an ill-defined disease.>>There are still people getting apricot pit enemas in Mexico to cure their cancer. Some people will believe anything.>>This I know less about. I'm still easing into the world of investment, and am eager to learn more about these aspects of business. (As an aside, are there good sources to get the scoop on a business' management, or is just a question of doing the right internet searches?) >>As TMF charly pointed out, you should check out their 10-K's. They've thrown Ampligen at everything from smallpox to bird flu to CFIDS to SARS to whatever is "hot" at the moment.I carried on an enormously long battle with HEB longs on the defunct HEB board back when HEB was worth shorting (~$7/sh). Like I said, it's not worth taking a position in now. If you want to gamble on it long, fine, but it's really just a day-trading stock (a "football" as old wall streeters would call it--just something to be kicked around/manipulated for fun and profit).D
Thanks for your wisdom regarding the company's financial history. I will have to dig into those a bit more...and learn more about technical aspects of businesses in general.One point regarding the placebo effect: CFS is known to be treatment-resistant. In fact, in 2005 a meta-analysis of treatment trials for CFS found that patients' placebo responses were lower than expected relative to most medical conditions (see http://www.ncbi.nlm.nih.gov/pubmed/15784798?ordinalpos=8&ito...The meta-analysis likely drew from some good and some mediocre studies, but its findings are consistent with physicians' experience treating CFS, and with the fact that CFS is chronic.Most well-planned treatment studies inevitably are able to find some weak or moderate improvements with the drug(s) - you know the sort, they use all sorts of pre- and post-test measures and scales, document whatever changes happen to be statistically significant, and conclude that the drug helps manage the disease, without curing it, and that future study is needed. Ampligen is the only drug I'm aware of that has produced complete and sustained recoveries in CFS patients, followed by long-term remissions when the drug is withdrawn and improvements when it's resumed. Not to mention the fact that there is a strong theoretical basis for why it works, regarding Rnase L and the antiviral pathway being upregulated in patients with CFS.*Think about it for a minute.* There are currently no drugs formally approved to treat CFS. Although many off-label drugs can help fight fatigue, none of them really cure the condition. Ampligen, the only pending CFS drug for FDA approval I'm aware of, works by fixing a specific mechanism of the immune system that's off in CFS, but not in other conditions (at least, not in other non-viral diseases).
re your comment:>Who are the researchers at the FDA who are going to approve this? Those >same incompetent ones. Whoops.That's exactly why the drug has taken so long to approve, and yes it's certainly an impediment to getting the drug approved, a reason not to buy HEB. But it's also a testament to the power of Ampligen that it's once again knocking at the FDA's door. Political roadblocks have hindered the status of Ampligen from the start, and a few still remain, but somehow the drug is still around. The initial FDA concerns (that the drug was too risky and had too many side-effects) were obviously unfounded, because now the drug is closer to approval than ever, as they're accepting an NDA for review.
hey good luck with this drug, you are fighting a mighty undertoe because no one really believes this is a serious illness.This is not a link comparing SSRI's to the drug, so I cant really determine if this diagnosis is "in a patients mind" or not... I still think this is a bs diagnosis, and if I see people who meet the criteria, I would prescribe Paxil rather than said drug. I doubt I stand alone in this Dx. Ampligin has alot of selling to do.
Heck even the CDC, who have a long history of downplaying the severity and stagnating research in the field (and still do), have this to say:"Symptoms and their consequences can be severe. CFS can be as disabling as multiple sclerosis, lupus, rheumatoid arthritis, congestive heart failure and similar chronic conditions. Symptom severity varies from patient to patient and may vary over time for an individual patient."They also write that CFS depression and bipolar need to be ruled out, and that "CFS is not caused by depression, although the two illnesses often coexist, and many patients with CFS have no psychiatric disorder."Mind you, this is the watered down version. Any treating physician in the field will tell you that the latter regarding depression has been known for years and isn't an issue anymore, and that the statement about symptom severity is soft for many of their worst patients, whose impairment more closely resembles late-stage AIDS or chemotherapy patients.Yes misconceptions abound, and a majority of the public don't think that CFS is serious. But the top doctors in the field, there is a logic to the science, and a clear line of reasoning for why Ampligen has gotten as far as it has, you just have to look a little beyond cdc.gov. It's exactly these misconceptions about CFS and how to treat it that, I suspect, are reflected in HEB's low price. Just thinking out loud (afterall I'm new at this)..It seems like you can take general confusion and misconceptions and say, "well it looks like a risky proposition"; or you can do some extra digging (especially if you're fluent in the field) to figure out why the confusion exists - Is it reflective of what CFS actually is, or is it reflective of merely people's perceptions of CFS? Could a diagnosis - creating impairment that apparently can range from congestive heart failure to late-stage HIV - really just be a sham? Are all the treating physicians who are pounding their heads over CFS (afterall, they've also conducted most of the best research) being fooled by patients who are just a little tired? I've been trying to think a lot about this, going back & forth. And so far I've come to the conclusion public misconceptions reflect people's perceptions of the illness, not the integrity of the construct. The diagnosis is serious and real as rain. And that the group of expert CFS physicians who aren't associated with the CDC know their stuff. For all those reasons I'm thinking that HEB is currently undervalued and that Ampligen will be a success.
But it's also a testament to the power of Ampligen that it's once again knocking at the FDA's door. Political roadblocks have hindered the status of Ampligen from the start, and a few still remain, but somehow the drug is still around.>>Substitute "Genasense" for "Ampligen," and you'll see the flaw in your analysis.
Thanks for the tip...looked up news on the drug. Is the idea that many products from small drug companies are over-hyped while they wait for FDA approval? It actually looks like things might be up for Genasense (http://www.marketwatch.com/news/story/fda-accepts-gentas-nda... but I see your point.I'm still trying to think like an investor [- I read the MF guide book, and figured I'd start with an index fund and a large cap. I haven't even spent much time analyzing potential picks...]But I do happen to a have a lot specialized knowledge about CFS, which compared to cancer treatments, has a more checkered past filled with public misunderstandings about CFS, which can be found everywhere (just scroll up a bit).Regardless of the strength of HEB, it seems like there is a world of relevant information that's not being incorporated into this company's analysis. Misunderstandings of CFS abound (just scroll up a bit), but I don't vision Wall Street incorporating them, to them it's just "another small drug, would be the first approved for its disease, being marketed in an if-y field, to potentially 4 million people".If anyone has time (and who does these days?) I'd recommend forgetting about HEB and the stock market and just reading up on CFS. A good yet light and entertaining description can be found here (http://www.davidsbell.com/Faces_of_CFS.pdf); you can piece together the history of the disease (which goes back, for all relevant purposes, only about 20-30 years) by reading blogs, advocacy websites, PUBMED articles, or even check out a well-known book called Osler's Web. Follow the paths of the original doctors in the field - it all makes an interesting story to say the least, these doctors have been put through the ringer: heartfelt tragedy for their afflicted patients, frustration towards the futility of their treatment efforts, alienation and scandal from their government, conducting hard-lined research on shoe-string budgets while being swamped with new patients atop old ones who are still sick, breakthroughs and revelations along the way of various sorts and sizes relating to etiology...Anywho.. if anyone's able to do that, I'd be curious about what he/she'd thinks. At the least, I think, it'll be clear that within the world of CFS, Ampligin is surely something different - in the book of CFS, it would have its own chapter, and it'd be the only drug that has its own chapter, even if it's never administered again. It's not another hyped-up drug (there's really no hype in CFS at all); in this context, it's often seen as a wonder drug that impressed even the most hardened, cynical and genuinely concerned physicians in the area, but somehow got left behind. A sad story of patients unnecessarily losing years of their lives, hopefully one that'll have a happy ending.
Regardless of the strength of HEB, it seems like there is a world of relevant information that's not being incorporated into this company's analysis. Misunderstandings of CFS abound>>Are you investing to prove a point about CFS or make money?Again, you have in this company a poorly-defined disease, notwithstanding your entreaties (there's no real endpoint, etc), a drug that's been kicked around for everything under the sun and failed in every setting, and suspect management.The market doesn't care what you think about CFS or what a few doctors think. The only thing that matters is how this thing could get approved. So far, that doesn't look promising.>>Thanks for the tip...looked up news on the drug. Is the idea that many products from small drug companies are over-hyped while they wait for FDA approval? It actually looks like things might be up for Genasense>>Nope, the idea is that a company with suspect management (Genta), throwing the drug at multiple indications with no success in any one of them (and a history of suspect endpoints), and that the company could never get its act together in making a decent NDA submission echoes HEB quite closely.D
>Are you investing to prove a point about CFS or make money?What's the difference? If CFS is a poorly defined construct, which is too ill-conceived to be treated, then HEB is a bad bet. If it's a solid construct with good research and theory (supporting the usage of an a specific immunomodulater), then HEB is a good bet. It doesn't matter what the market thinks about HEB, it matters what the few expert physicians who are going to use drug think about it. Any discrepancy between the two (the market vs select physicians) is what makes HEB either over or undervalued.Ampligen's clinical efficacy is not really debated in the field of CFS. It's not a complicated field - in the late 80's during the Ampligen trials for CFS, there were maybe 3-5 well-known experts in the field. By now there are about 10-20, along with more who are under radar. A number of the older doctors have faded out with age, to some it was useless to go on when they had found the cure. They'll give speeches or write articles here or there, and my sense is that collectively there's a strong sense that Ampligen's the cure or the closest they've come to the cure, but they're just like 'what's the point anymore?'That's not to say that the drug will get approved (although you can be sure what all the advocacy groups will be doing during the review). Just that the market's general consensus is off.
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