Chevrolet Impala (via Wikimedia Commons)
[Swivelchair note: This post was originally published 01.08.08, and this is an update 03.10.08 in view of the renewed interest in weight loss meds, see here, and here, for example]. The JP Morgan Health Care conference is coming up, where biotechs present their research and business developments.
I’m sure a lot of weight loss meds will be presented. I’ve worked in this area for quite a while, and there seems to be a serious disconnect between data (I mean, facts) and feelings (like, what’s right and wrong). This may be a truthiness situation.
For years, I’ve sat in conference rooms and listened to expert endocrinologists say the same thing: Fat deposition — obesity or fat tissue distribution on the body — is predominantly hereditary. There is a behavioral component — which, last I checked, resulted in plus or minus 10% or so change. But for the most part, if your parents were giraffes, that’s what you’ll be. If they were hippos, that’s what you’ll be.
To me, the gold standard — well, ok, maybe the 10K gold standard — well, ok, the Home Shopping Network gold standard — for weight loss meds is Phen-fen. Now, I posted on this here, and here explaining what I mean by that.
In the 10+ years since Phen-fen was banned, science as marched on, and we figured out what serotonin receptor subunits – subunits are on the heart — so now we know how to avoid them. (Explained before). Lorcaserin was screened for that in drug development. Sort of a yawner in terms of science, imo. (This is from the website and is my interpretation).
So, lorcaserin is a totally new chemical entity — like Phen-fen without the scatter-shot serotonin receptor approach — it pretty much avoids heart serotonin receptors, and is selective for the serotonin receptor subunit-subunit within the brain. OK, mode of action pretty much figured out. [Swivelchair addendum 03.10.08: The 5-HT2C specificity was previously discussed here and the chemical structure is presented in Smith et al. cited below]
Is this totally the perfect drug? No. It probably acts a lot like Phen-fen, which had some additional side effects (like, potential dry mouth, dizziness, insomnia). But if you’re taking this stuff every six months or so to keep off 20 lbs, you’ll suffer that kind of thing (I’m guessing).[Swivelchair note 03.10.08: I'm totally guessing that this will be a diphasic dosing regime -- people will dose to lose weight, and then take only as a maintenance dose to keep the weight off as needed. Again, nothing anyone else has said indicates this, but that's how I would self dose if I were taking it.].
Like I said, it’s a Chevy, not a Maybach. A Maybach, your fat would melt in about a week, you could eat whatever you want and your calories would turn to muscle and bone and energy, and not fat, and you’d look 15 years younger and you’d be smarter and richer and better looking and more popular.
[Swivelchair note 03.10.08: The following I think is interesting in terms of the biopharma business -- this drug is a safe version of one previously on the market that was a runaway best-seller. If negative reputation of the "primitive phen-fen" can be overcome by launching "targeted, accurate and safe son-of-phen-fen" then you pretty much can forecast the market size. I don't know, but those must have been interesting meetings in the board room. ]
From an industry perspective, this is the perfect storm: you have the market data already. You know how big the market is.
You already know market acceptability. Maybe the trouble is, “Hey, there’s the Phen-fen taint — no one will prescribe this stuff because they don’t want to be sued.” Don’t know, but plenty of other product-liability second generation products did just fine. IUD’s come to mind. [Swivelchaire note 03.10.08: And Celgene's thalidomide compositions]. Plus, obviously the eat-less-exercise-more gig is a miserable failure. What doc wouldn’t lurve to be a hero when their patients start losing weight?
You already know safety and efficacy — if the heart receptor binding is eliminated. You know pretty much about any other side effects. Efficacy should be the same as Phen-fen, which sold like gangbusters. (The phase III’s aren’t complete, and I have no idea what the data look like or how it will be crunched).
And, you know mode of action, pretty much — that’s better than 90% of the drugs out there that work, but we have no idea why.
And, you have virtually no competition in probably the largest therapeutic area ever (but who knows what’s coming up on the heels of lorcaserin.) [Swivelchaire note 03.10.08: To me, when I compare this to, say, leptin or other injectables, it's a no-brainer. First, the placebo vs. drug data will be much cleaner, because I think the placebo effect of an injectable is much bigger and longer lasting than that of a pill. (I have no data for that, just a hunch). So injectables may have fewer side effects (especially if they're natural proteins), but who cares if you can't tell if they're effective. Plus, who is going to want a daily injection? No one. OK, maybe diabetic people already on insulin. Which leads me to a conspiracy theory: are all those drug makers in the diabetes market conspiring to make the FDA hurdles so high that perfectly usable weight loss drugs can't get approval? I mean, having everyone lose weigh all of a sudden really makes those marketing types go back to their forecasts and re -do the NPV's of the diabetes pipeline, probably].
And the market is growing (to make a lame, offensive, double entendre).
I think this is a case where the FDA should lower trial requirements and speed up approval.
The FDA instead has lots of resources devoted to “eat less exercise more.” Duh. Do they really think people didn’t know that?
Or is this a case of truthiness — they feel that obesity is a moral failing or failing of self-control so that a drug is cheating.
[Swivelchair addendum 03.10.08: It looks like public sentiment is coming around that weight loss meds aren't just "cheating", check out the public comments on the Newsweek articles referenced above. (see here, and here)]
Full disclosure, I invest, long mostly, in a variety of biotech companies that have anti-obesity meds in the pipeline, including the one that makes lorcaserin. With the market as it is, I’m getting wiped out — so if this blog raises the stock price of anything (which it shouldn’t or else something is seriously wrong with our markets), good.
More full disclosure — I have no inside information whatsoever, and am only going on what is in the publicly-available databases or business news, etc. Nothing here should be interpreted as any kind of recommendation to take any kind of health roll-of-the-dice or money-roll-of-the-dice with anything I’m writing here. Frankly, I’m just paranoid that someone will come back and say, “Swivelchair caused me to take this poisonous medicine! Sue!” or whatever. Nope, of course you are a grown up and have free will and can make your own decisions about your money or your body.
Smith, B.M., Smith, J.M., Tsai, J.H., Schultz, J.A., Gilson, C.A., Estrada, S.A., Chen, R.R., Park, D.M., Prieto, E.B., Gallardo, C.S., Sengupta, D., Dosa, P.I., Covel, J.A., Ren, A., Webb, R.R., Beeley, N.R., Martin, M., Morgan, M., Espitia, S., Saldana, H.R., Bjenning, C., Whelan, K.T., Grottick, A.J., Menzaghi, F., Thomsen, W.J. (2008). Discovery and Structure−Activity Relationship of (1R)-8-Chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a Selective Serotonin 5-HT2C Receptor Agonist for the Treatment of Obesity. Journal of Medicinal Chemistry, 51(2), 305-313. DOI: 10.1021/jm0709034
Swivel,
Above you said:
“One interesting thing an anesthesiologist just told me – it’s not unusual for smokers to not get nauseated with general anesthetic. This is because smokers have reduced serotonin receptors in the gut….”
I have read some stuff that indicates that smoking actually has somewhat of a selective MAOI effect. It is selective in that it doesn’t cause you to be tyramine sensitive, but it does otherwise provide some MAOI effect. Seriously, if you ignore the bad effects of smoking (which are hugely worse than the benefits) and only look at the benefits of smoking, it looks pretty good. It cuts your appetite, it causes you to lose weight, it perks you up, etc. But I digress.
Anyway, I thinkthe MAOI effect is what is likely responsible for the anti-nausea effect of smoking, although I have not researched it.
At the start of her rant, I thought Sandra was just one of those “Being overweight is just because you don’t stop eating” kind of rants given by thin people who find it easy to control what they eat and therefore believe that everyone should find it equally easy. Reading further into her post, I agree that something is up. She is either a shill or a loon. She seems to know a lot, yet she is intentionally distorting. Her first point about the sexual side effects is a perfect example. Things that work on 5HT2 actually have sexually positive side effects. I’m not sure which of the 5HT2 subtypes cause that, so I have no idea if that is a side effect here with lorcaserin or not.
I know that you have access to the logs, and perhaps you saw that Sandra and Devin posted from the same IP address. If not, I think you have misunderstood what Devin was trying to say.
I think he was saying that the medication is working, that at first Alisa recognized that it was working, but now believes that she is losing the weight through her own efforts.
I think it’s his last sentence that makes his message hard to get. He says:
“The drug is known to cause you to feel full. No one is trying to sell drugs that dont work or are unsafe. Obesity is a huge problem in the USA. Nearly everyone is fat, and its because of overeating.”
I don’t think that he is suggesting here that overeating is a moral failure, I think he is saying that if you eat less you will lose weight, and that he is saying it because he thinks that Alisa thinks that it’s her own efforts causing her to lose weight. He seems overall to be a supporter of Lorcaserin and not a supporter of Alisa. I see nothing in his post that is so strong that would even hint that he is a shill.
Again, you have access to the logs, so maybe you can see that they posted from the same address. Otherwise, I really do feel that you have misunderstood what Devin said.
And just in case you are wondering, I am not Devin, or anyone else who has posted on this entry. In fact, as far as I know, I’ve never posted anywhere on your blog before.
Thanks for the comment Itsme. (Is your cousin ItsIts, the ice cream?)
The smoking/weight loss effect I don’t think has been seriously studied. Smoking steadies the nerves and cuts the appetite. Is it druggable?
As to the comments by others, here’s the usual disclaimer: don’t anyone believe anything here, go to the official sources for official information.
I’ll put up a privacy policy, but seriously, I get back-room e mails from people, that may color my remarks out here in public. The comments are what they are, and everyone can form their own opinions.
As to the smoking and serotonin, I agree — except for the hideous artifactual side effects, could tobacco be “druggable”? I’ve got some PubMed research in other tabs pulled up in my browser now, and it’s pretty interesting.
I am not “Devin”, and I have no idea who Devin is. There seems to be a lot of paranoia here!
I have been overweight all of my life, since grade 2. Not excessively though, about 20-40 pounds, depending on what else was going on in my life. But even though I wasn’t excessively overweight I suffered a great deal because of it. So many other people made me feel like I was the biggest loser in the world just because I had some extra fat on me, my intelligence, talents, or other positive characteristics didn’t matter. All that mattered was that I wasn’t thin. It took me many many years to get over it.
I could have easily been one of the poor victims of the Phen-Fen fiasco. I wanted very badly to lose weight at that time, but despite my liberal attitude about recreational drugs, I was completely anti-drug when it came to weight loss, because I understood from all of my dieting experience that losing weight is easy, keeping it off is difficult, and keeping it off requires a total change of habits and mindset. A drug cannot help there.
So fortunately for me I didn’t get caught up in the Phen-Fen mess. I wonder if any of the rest of you really know what happened with those drugs. You should read Alicia Mundy’s “Dispensing With The Truth”. You will read about Wyeth deliberately misreporting serious adverse effects of fenfluramine, how they dressed up their sales force in lab coats so they would look scientific and hosted drug sales shows at women’s gyms all over the US. There were plenty of docs who were writing hundreds of prescriptions per week, “prescription mills”. So much more, please read the book. It will give you much insight into the potential pitfalls of loracaserin. If you care.
Who benefits from these drugs? The patients ? I think not. The drug companies, absolutely. This must be made clear. If you are trying to justify lorcaserin as a legitimate weight loss drug, well good luck. A person can lose just as much weight without the drug. When people stop taking lorcaserin or any other drug, they regain the weight. So what good is it for ? Mix in potential side effects, loss of sexual appetite, dizziness, what about more serious effects like we saw with fen … primary pulmonary hypertension (incurable and fatal), valvulopathy (usually requiring valve replacement) … to lose some weight? How can we do this to people?
If you are looking at lorcaserin as an vehicle for making money, by investing in Arena, then you probably made a good choice. Most people don’t know the story behind fen and have their heads in the sand when it comes to what works for weight loss, so they’ll happily jump on this latest drug bandwagon. Arena will make a mint, and so will its investors.
I have mixed feelings about investing in a drug that I think is at best a waste of consumers’ money and at worst damaging. But if I don’t do it, others will. Why should I be so altruistic?
I’m hardly a “loon”. I think I know so much more than any of you. It’s a complex situation.
Honestly, read Mundy’s book. You will be enlightened. And no, I’m not Alicia Mundy !
Regarding smoking and weight loss … it’s no secret that many many women smoke to keep their weight down. In fact I would bet that the vast majority of thin women over 30 are smokers. I don’t know that it actually suppresses the appetite, I think the smokers consciously light up a cig in order to avoid eating. I do the same thing with coffee.
I think we’d all agree that cigarette smoking is far worse for you than some extra fat. The CDC found that overweight is actually GOOD for you:
“Being overweight (BMI of 25-29.9) was not associated with excess mortality. The study found that 87,000 fewer deaths than expected were associated with being overweight.”
http://www.cdc.gov/od/oc/media/pressrel/fs050419.htm
Analysis of existing data has shown that even mild obesity does not have a significant health impact. But look at the weight loss drug ads. I can hardly wait for lorcaserin to be approved so I can see the justification for it. The ads always blast misinformation that overweight and obesity are necessarily killers. Because if they aren’t, there would hardly be a reason to take a prescription drug, right? You should have an actual problem first, you know. It’s unethical to treat healthy people with serious prescription drugs.
Sandra, I disagree with just about every conclusion you draw from your facts (and I haven’t checked out your facts). But, in the spirit of reaching across, metaphorically, from the “no meds for weight loss” aisle to the “yes meds for weight loss” aisle, your comments are duly noted.
Message from a paranoid blogger (moi): I have no idea who Sandra is, and of course don’t make any material decisions about money or health based on any blog including this one.
I have a new post up about obesity — a theory that environmental arsenic affects thyroid-mediated gene regulation, and possibly contributes to obesity. It’s a stretch, but here’s the link:
http://neurologicalcorrelates.com/wordpress/2008/11/06/does-environmental-arsenic-contamination-cause-obesity-by-disrupting-thyroid-hormone-mediated-gene-regulation/
Nobody should be paranoid about me. I’m just a regular person from a connections perspective. But I am not regular from a knowledge perspective. I am highly suspicious of prescription drugs, all of them, and weight loss drugs in particular. You should see my rants about anti-depressants and drugs for the so-called ADD and ADHD. They all fall under the category of “the drug doesn’t solve the fundamental problem”.
I would love obesity to be caused by something environmental, but I honestly believe there is a much simpler explanation: massive quantities of easily available high-calorie foods + incessant slick advertisement of these foods.
We don’t see obesity in populations until they start having wide access to junky high-calorie foods. It appears that high-fat high-calorie foods are worse than high-sugar high-calorie foods.
My overweight was caused by getting addicted to “convenience” foods, mostly sugary crap, in the mid-1960′s when I was a young kid. There were very very few overweight kids then, I guess my family was one of the first to purchase junk food. Fortunately I’m the only one who had a problem with it.
If the problem were environmental, I would have expected to see more overweight kids. It’s not like I lived next to an arsenic factory.
I lived in the same neighborhood as my skinny friends.
The problem is that we overweight people eat too much and at some point we get physiologically hooked food, or hooked on certain types of foods. My drug of choice is anything with sugar. Scientists and doctors say you can’t get addicted to food. Well, the junk is many times not so much food, you know? Like what part of a twinkie is “food” ? Just because I can eat it, doesn’t make it food.
Also an argument against the environmental explanation: I don’t have a problem losing weight, at least not physiologically. When I don’t eat, or don’t eat so much, I lose weight. The problem is the cravings. I am driven to eat.
By the way, I want to correct a statement I made in a prior post. I think I know more about overweight, obesity, and weight loss drugs than anyone else posting here, except you. You clearly know a lot, not sure if you’ve ever been overweight or obese though, so I don’t know if you understand just how bad the cravings get.
I see that rimonabant (Acomplia) is toast. It was determined that the side effects outweighed the weight loss benefit. Sanofis didn’t even complete Phase III trials. Looking at Phase II data, people on the highest dose (20mg) lost an average of 14 pounds in a year. In a year! That’s pretty bad. And as it is with other drugs, the weight was regained when the people stopped taking it.
Sandra thank you again, your views are nothing if not consistent.
Hey Arena Pharmaceuticals Board of Directors – handing out golden parachutes for change in control? Making it public New Years’ Eve? C’mon.
You know the deal: if the company is sold the exec. suite gets taken care of. 2 years health bennies, lotsa cash, couple years salary, full vesting of options. Better deal than if the company stays independent.
So, if I’m in the executive suite, and I’m say, in my 60′s, and this is my last hurrah, and I get paid a big wad of cash if I go away and play golf, or, I could stick around, and actually work and have the possibility of getting less money (if salaries are rolled back to pre-bubble levels). . . hmmm. . . work less, get more. . . or work more, get less. . .
Even in the event of death of executive (heaven forbid, I mean no one wishes that) but really, how about life insurance for the family, instead of shareholder money? Or, are the death vesting options on top of life insurance? How nice for the family, and how magnanimous of the BOD to donate shareholder money for this. How ’bout the BOD pays out of pocket their own money?
Oh, the comp consultant paperwork covers the diligence. Isn’t there that comp consultant who advises other companies for the same BOD members?
Or, same comp consultant for both the target and the acquirer? Sweeten the pot to encourage the buy out?
I’m guessing, I have no idea if there even would be a buy out, but hey, this is a 12/31 filing for a golden parachute change of control agreement.
The dilution to pay for the clinicals by shelf registrations, OK, I get that. Selling out convertibles to raise cash, OK I get that.
This is optics — to be clear — not that anyone is doing anything illegal, or even violating the fiduciary standards they are held to. I have no idea. But, a New Year’s eve filing for a nice, juicy golden parachute/change in control agreement?
So, let’s review: Nice golden parachute agreements filed New Year’s Eve in era where P/E multiples are compressing and company has no profits is basically cash value. Unknown if comp. consultant is a tool by potential acquiring company to sweeten the pot so execs agree to lower share price for buy out.
Color me cynical. BOD, same ol’ La Jolla shenanigans? I was so hopeful things would change down there.
http://www.sec.gov/Archives/edgar/data/1080709/000110465908079122/a08-31127_1ex10d2.htm
Look, they updated the agreement to comply with the law. >:-) At least *primarily*.
===================
“On December 30, 2008, we amended and restated the Termination Protection Agreements, originally effective on December 20, 2002, and the Severance Benefit Plan, originally effective on January 20, 2006, primarily to bring them into compliance with Section 409A of the Internal Revenue Code of 1986, as amended, and the regulations and other guidance promulgated thereunder (“Section 409A”). The executive officers that are a party to a Termination Protection Agreement include Jack Lief, Dominic P. Behan, Ph.D., Robert E. Hoffman and Steven W. Spector, and the participants under the Severance Benefit Plan are such executive officers and William R. Shanahan, Jr., M.D.
The amendments to the Termination Protection Agreements, which require a change in control to trigger benefits, include (1) delaying cash payment until the earlier of (i) the first business day that is six months following the employee’s termination or (ii) following the employee’s termination, the employee’s death; (2) modifying the good reason definition relating to the relocation of the employee’s principal office or place of business required to trigger the benefits; (3) adding a waiver and release as a condition to receiving severance benefits; and (4) adding Section 409A compliance provisions.
The amendments to the Severance Benefit Plan include (1) delaying cash payment until the earlier of (i) the first business day that is six months following the employee’s termination or (ii) following the employee’s termination, the employee’s death; (2) modifying the good reason definition relating to the relocation of the employee’s principal office or place of business required to trigger the benefits; (3) adding a deadline for turning in the waiver and release that is required as a condition to receiving severance benefits; and
(4) modifying the Section 409A compliance provisions.
The foregoing description of the amendments to the Severance Benefit Plan and the Termination Protection Agreements is qualified in its entirety by reference to the Amended and Restated Severance Benefit Plan attached hereto as Exhibit 10.1 and the form of the Amended and Restated Termination Protection Agreement attached hereto as Exhibit 10.2, both of which are incorporated herein by reference.”
======
This agreement affects 5 of the 7 execs.
Lief is the Chairman, President, and CEO
Behan is a VP and Chief Scientific Officer
Hoffman is a VP and Chief Financial Officer
Spector is a VP and General Counsel
Shanahan is a VP and Chief Medical Officer
Judging purely by their photos on the Arena web site, only Lief appears to be old enough to wish to retire.
http://www.arenapharm.com/wt/page/officers.html
This weekmarks the end of my 2 year participation in the Arena Lorcaserin study. I have lost about 90 lbs., can actually exercise (though I still don’t like to exercise but at least exercising no longer causes me to be so uncomfortable) and I can look in the mirror without flinching. I have not really had any side effects from the drug and would like to stay on it for a longer time. Of particular note was the fact that I cannot stand to eat chocolate or fried foods. They both make me nauseated. Quite a change from the dark chocolate gobbling junkie I was prior to the program.
I don’t enjoy the weigh-ins even though for the most part the numbers have gotten smaller. At mid-study I was assigned a new “advisor” who was a bit of a dick and so I complained the the supervisor, noting that after 12 months I KNEW what I had to do and if I TOLD the advisor that I was bloated (salty food was the culprit) he had to at least pretend to believe me. I guess the supervisor intervened (particularly when at the next weigh in I was 5 pounds lighter) and the adviosr became, at my request, a cheerleader as opposed to the whistle-blowing coach.
I’m so glad I got into the study, though a great deal of determination went along with it. I’m concerned about what the near future will bring. I am in the habit of exercising and understand the need to control what I eat but for the last 2 years food has been an afterthought, something I did because I needed to eat to keep going.
Will being off the drug change all that??
Congratulations Zade – one of my coworkers, who actually directed me to the study, has just completed his second year. He’s pretty sure he was on the pill for the first year, lost 40 pounds with no particular effort, but has regained the whole thing after the second year, which he’s sure is the placebo.
I’m just completing my first week in the study, and haven’t even weighed in yet, but as a diabetic, I’m thrilled to say my blood sugar’s nearly down to normal from sky high a week ago. I definitely find my appetite’s greatly reduced and I have to structure my eating to ensure I don’t forget meals. Someone mentioned the mental/emotional side of the equation – I don’t know what other people have encountered but my screening contained quite a few questions regarding my state of depression (on a 0 to 10 scale, I had 0 – i.e. not at all depressed). Apparently the drug has been known to cause depression. The study I’m in is 50/50 between placebo and 10 mg. of Lorcaserin twice a day.
Swivel – thank you so much for this blogspot – it’s been really interesting reading the take of others on this drug.
Hello everyone. Sorry for being delinquent in not responding sooner.
Sandra, Sandra, Sandra (said Bradybunch-esque style), why the New Year’s Eve filing? I still think the product is good (from public information,etc., imo). But, seriously. Trying to slide in a goody-laden exec. golden parachute agreement on New Year’s Eve is about par for the course for that whole La Jolla bio crowd (if you know what I mean and I think you do). (And you know who you are. . .) It’s like 10x tackier than a Friday close of business before a 3 day weekend filing. C’mon. At least the company could’ve filed in paper, like Google, to throw a log in the road against being found out immediately. http://www.sec.gov/Archives/edgar/data/1288776/999999999708048909/9999999997-08-048909-index.htm
Moving on.
Zade and Millie, as always, I have to hedge here, and say I have no idea if you are for real (sorry). Anyway, assuming you both are truly enrolled, thank you for being in a clinical trial. It really does amaze me when people — even if paid — volunteer.
Zade, the data showed that stopping drug was correlated with weight gain , so I would think that appetite increase would similarly be correlated. Have you asked your investigator/company sponsor? The only valid information comes directly from the sponsor or the docs (or maybe the FDA), to be sure, and usually clinical trial sponsors are pretty good about answering questions.
In what way was your first advisor a “dick”? I’m just curious. You’d think that the sponsor would be treating the enrolled subjects like royalty, to prevent drop outs (which could screw up the data).
Millie, after a week, I wonder if the appetite suppression is a placebo effect. Interesting.
I wonder about the 2x a day dosing (as well as potential additional compositions for co-dosing to increase efficacy). Is there a placebo effect 2 x with each placebo dose? Or one big placebo effect for the entire day? (Not that you’re on placebo, this is just a general question).
And you’re welcome for this blog posting, but, the credit goes to you. I was originally interested in the pharma-biz end of this drug — and clinical trial subjects (presumably) began posting. Interesting lesson for commercial sponsors of clinical trials. To be faculty-lounge-ish, one may academically query if gag clauses in informed consent enrollment agreements are restraints against speech violating the First Amendment?
(Actually, one “subject” requested that I remove her posts, so the previous comments are a bit confusing, as they respond to her posts).
Arena Pharmaceuticals: Why not put up your own blog for this? I’m a random blogger. Wouldn’t it be better if enrollees in your clinical trials could post comments that your experts could address? (Anyone: if there is a sponsor blog, let me know and I’ll post the link).
Thanks for the comments everyone.
Hi Swivel,
Obviously I can protest to the heavens that I’m real, but while I’m assigned a PIN by Arena, I don’t know if there’s any way it can generate any kind of confirmation that it’s legitimate!
As for doubling the placebo effect, I don’t know. I also don’t know if the effect, real or imagined, is sustained, or only within the prescribed hour or so after taking the pill. I’ve forgotten to take the pill twice so far (taking it as soon as I remembered, but after eating), and I still found my appetite to be far less than it was, so I think it has to be at least partly suggestion (by the way, I was a heavy smoker who quit cold after one hypnotic session 20 years ago, so I know I’m VERY suggestible).
As for volunteering, I’m grateful to have the opportunity and it’s not all about the $740 I’m being paid over the course of a year…the screening alone included close to a thousand bucks worth of medical tests that I’d never have had done otherwise. Knowing that my heart and lungs are in excellent shape for my age (I’m at the outer range of the study parameters – I turned 65 as I was starting it) is a comforting thought. It’s also doing something else I’d hoped would happen – it’s making me monitor myself much more closely than I had been. Between journaling all food intake and monitoring my blood glucose levels, placebo or drug, I’m feeling in control again. Empowerment is a very good thing.
Oops, sorry, I should have mentioned this before – maybe it’s my aging memory, but I don’t recall any gag clause in my consent agreement. I have to root around for my copy and double check it, but I think that would stick in my mind.
As for it’s first amendment implications, I don’t think that would fly – it would be voluntary consent, and if I felt it was a problem I’d have the choice not to agree and opt out of the clinical trial.
Hi Millie, again, apologies if you are for real — I hope you understand the need for disclaimers here. . .
That seriously is pretty amazing that you were able to quit smoking after one hypnotherapy session.
Interesting that you still weren’t hungry even though you missed doses 2x — different days? I guess there’s a 1x day dose that also shows weight loss. Perhaps lack of appetite for missing a single dose on the 2x a day is just a matter of degree — similar to if you were on the 1x a day dose. Or could be your super-suggestibility and maybe they hypnotized you when you weren’t looking. . . ;P
Hey Millie, if you’re 65+, and commenting on a blog, more power to you. Of course, as a blogger my view is that blogging is in the public interest (even if some days are better than others. . . ) and so thank you for exercising your First Amendment Rights and commenting here. And good for you if being in the trial gets you more empowered in your own health care.
First Amendment or no, you all know the drill — I have no idea if anything anyone posts here is for real, so don’t make any health or financial decisions based on this blog. . .
Welcome Stock Gumshoe readers —
Well. . . sort of welcome. Please know that nothing on this blog should be taken as any kind of investment advice or medical advice.
I have no way of knowing who is for real and who is not, including those who say they are participating in clinical trials.
Absolutely nothing, and I mean nothing, is meant to pass along any facts not so stated by an official source of information like the drug sponsor or the FDA. The rest is my opinion. (If there is any inaccurate information, please let me know. . . ). I am very concerned when investment advice is given based on some comments posted here. Seriously, I’m in a bind whether to take down the comments (because I don’t know whether they’re for real) or leave them up (because taking them down may itself be construed as some sort of message).
Sorry being paranoid, but you know how it is. Swivelchair
How does Zade know that he/she was taking lorcaserin ? It’s a double-blind study.
Pharmaceutical companies design placebos to mimic some of the real drugs’ side effects. So just because a person lost their appetite or felt some other effect doesn’t mean they were taking the drug.
Sandra, you can’t design a placebo to mimic side effects. That’s the fallacy of double blind clinical trials when distinct effects are expected. Don’t see them and you know you’re on placebo. Perhaps that changes a persons attitude or lead them to drop out of the study.
Aaron, I don’t know if distinct effects were originally expected given the novel dosing, even if the mode of action was very well characterized. I mean, lorcaserin at 20 mg/bid could have been as efficacious as sugar pills.
I think the safety was expected, e.g., no cardio receptor binding.
Normally, where there is an existing standard of care, you can’t run a placebo controlled trial at all.
It would be unethical to deny people in need of treatment. I guess you could argue that the real pepsi-challenge should have been sibutramine non-inferiority.
But I just don’t think the FDA sees obesity as anything more than a lifestyle choice, despite all data to the contrary. Like depression used to be.
Here’s my question: Why is the FDA so slow on the uptake on this?
Isn’t there a real life reporter who can do some digging on this one? Are diabetes med pharmas lobbying to put off having a decent weight loss med on the market?
They’re only testing for heart problems. What if this drug has some action on a part of the brain, or lungs, or some other important organ? I worry about that.
Placebos are most definitely designed to mimic side effects of the active drug. The term is “active placebo”, you can find lots of info on the ‘net.
Interesting point about the ethics of giving an obese trial participant a placebo instead of the active drug. This makes the pharmaceutical companies hypcrites, because on one hand they all claim that obesity is this dangerous problem that must be mitigated (always forcefully presented in their literature), but on the other hand they are willfully withholding what ought to be “necessary” medication.
I’m wondering why the groceries stores are filled with so much junk food. I wish someone could do a study to figure out what percentage of “food” in a grocery store is actually reasonably nutritious. I saw an interesting program on TV, maybe an Independent Lens episode ?, that showed a young girl in LA who has to take 2 buses to get to a decent grocery store that offers fresh fruits and veggies and good meats because the few stores in her neighborhood have nothing but crap, and the neighborhood is also infested with fast “food” joints. I think the girl’s round trip just for transportation, not including actual shopping, was like 2 hours. And then we wonder why people are fat. Heck, I walk to work and pass 3 Dunkin Donuts and several other shops that have nothing but sugary sh*t in them, some with signs outside advertising their confections. People probably want to think I have no willpower when in fact my willpower is tremendous, I’m an addict and yet every day I make it to and from work walking through this minefield.
First of all, I got a fully disclosure, that I am ARNA’s shareholder and so my post can be considered BIAS and not neutral,
but I’ll let the reader judge on that
Sandra,
you obviously do not understand FDA trial design in general and specifically on Lorcaserin trial.
The Placebo here is not active placebo.
and you said that the placebo was design to mimic the side effect of the drug, but
how do you know about the side effect of the drug before you done large scale clinical trial ?
The Placebo in Lorcaserin trial is made to look exactly like the real drug.(in shape and color).But of course it is just an inert substance that do not have any effect at all,
because if the placebo had some efficacy or some side effect, then
they would not be able to get the result in controllable manner, and will never able to get Statistically significant result…
Regarding the effect on brain or lungs or some other important organ,
if Lorcaserin shown any adverse event on those organ, I am sure the doctor would be able to pick it up, especially with more then 7000 patients in the Two Large Phase 3 trial… An abnormal Brain, Lungs function would be easy to monitor if they occur
so the fact that they do not occur, means Lorcaserin is safe to those Vital Organ
and ARNA trial, specifically check on the heart valve, because this is where “Fen” failed,
and Lorcaserin target same receptor as Fen did, but 100 times more selective and avoid targeting the other receptor that cause Heart Valve problem like the one from Fen.
of course the focus on Heart Valve is important here…
Why do you say the pharma is hypocrite?
if they give all the patients the active drug, then they would not be able to compare and prove that their drug is good in EFFICACY and SAFETY.
That is why they need some patients to take placebo.
and it is required by The FDA, the Law and I am sure all the Medical Doctor in this world would PREFER any drug trial to have placebo for comparison purpose.
There are some trial namely antibiotics trial that do not require Placebo, but
what they did is using the known and approved antibiotics in place of Placebo, and compare their efficacy with the new drug in the trial.This is called Non Inferiority Trial using Active Comparator (but not placebo).
Thank you BTM for your comment and excuse my having to put up a disclaimer that I haven’t fact checked your remark. (Sorry).
“Sandra,” response?
Question if you know: will lorcaserin be used off-label with amphetamines? Any phen-lorc trials in the works?
I took Lorcaserin in a study (20, 40, and 60mg doses) in Canada. It has some initial good effects, but the overall dose is NO GOOD. MAJOR headaches, headaches on all levels, and also it feels just horrible in your system.
AVOID this drug at all costs. More immune bodies may enjoy this drug. BUT, it is a different feeling – seems like a different drug – at different doses!
either the 20 or 40 was great! (its a double blind study) but the others were AHHHHHH horrible!
Test subject,
Come clean here. No 40 mg or 60 mg lorcaserin trials exist. What’s up?
Readers: if test subject doesn’t respond, I’m taking down this post because it is facially incredible.
Hi Swivelchair,
Sorry took a while for me to respond back,
but so far there are no Phen-Lorc trial in the works.
Still, I think there could be this kind of trial in the future, of course after Lorcaserin is approved by FDA.
Best regards,
Biotechs_Maven
Thanks for the update Biotechs Maven.
Hi Swivelchair,
I just sent you an e-mail…
I click the link on the e-mail on this webpage.
Hope it is your correct e-mail
Thanks,
Best regards,
Biotechs_Maven
Got it, thank you.
biotechs_maven, how can you be sure that the lorcaserin trial placebo was totally inactive? Pharmaceutical companies often tailor placebos to mimic side effects of the active drug, presumably to make it more difficult for the placebo group to determine that they received the placebo. Do you have specific knowledge about the lorcaserin trial? Or were you making a generic comment? If the latter, do a search on “active placebo”.
I am also suspicious of test subject’s post.
I can’t imagine combining phen with anything. Have you ever taken that stuff? It’s old school speed and *very* clunky. Nasty side effects. Headaches, increased BP and heart rate, insomnia, constipation. I think the appetite reduction comes more from feeling weird and drugged-up than from a true direct action on any appetite drivers. Probably have a much better time and lose more weight using MDMA. It’s time to retire phen.
I completed the 2 year BLOOM study and lost 45 pounds (22% of initial weight). I went from barely being able to walk a mile to now running 25+ miles a week. My suspicion that I was on placebo was confirmed when Arena had to unblind me POST-study because of heart valve changes. Fortunately for lorcaserin, I was NOT on the active drug. It’s refreshing to know I lost the weight on my own with the encouragement of the study center staff who I found to be great motivators.
Thank you On My Own for your comments.(Sorry but I have to include the disclaimer that I don’t know who here is for real and who isn’t.)
Question: Why were you suspicious that you were on placebo?
Let’s do your math:
Initial weight = 223 or so
Final weight = 223-45 = 178 Final weight
45 lbs = 22% of initial weight / 22.25 lbs = 10%
Hopefully you can keep the weight off on your own once the study ends and you may not have access to motivators at the study center.
Hey swivelchair, notice that OMO says that BLOOM was a 2 year study. So back to that other thread where you and someone else said BLOOM was 1 year … why the discrepancy? Why would BLOOM be a 2-year study and yet Arena is publishing 1 year weight loss results?
Here’s the link to clinical trials.gov BLOOM, and here’s the explanation:
I was on the one year Study and lost 32 Ibs from starting weight of 250. I took two 10 milligram tablets a day and lost an average of 2- 3 lbs per month with no side effects. Excellent product and I will recommend to anyone once FDA approved. In fact I intend on taking it again when it comes out to assist with the rest of the weight that I still wish to lose.
Connie, are you unblinded? Do you know if you were on drug or placebo?
My opinion is a bit another how it’s possible to talk to the author, for instance on an e-mail?
Superb website…
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