« What motivates child animal abusers who grow into violent adults | Home | Bullying and Harrassment in the Restaurant Industry Bork Bork Bork »
(Updated) Lorcaserin - probably the “Chevy” of weight loss meds, but victim of “truthiness”?
By swivelchair | March 10, 2008
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
Sphere: Related ContentTopics: Behavior, Conditions or Diagnosis, Neuromarketing, Neuropolitics, Obesity, Seven deadly sins, gluttony |
January 8th, 2008 at 12:53 am
The patient takes how much for how long twice a year to keep 20lbs off? The side-effects only last while the meds are being taken? Does taking it four times a year, say make any difference? I’m not asking for myself, you understand, but I have this friend.
January 8th, 2008 at 9:33 am
Heh, . . gee, why does do my jeans shrink after Christmas every year? . . .
Yikes, what I meant was that it would probably be dosed daily until you reach a target weight, and then stop the meds — and go on a maintenance dose every six months or so to keep the weight off. I’m guessing. Unless there was some kind of warning against it, I would probably self-dose this way, just because there probably will be the Phen-fen type side effects (dry mouth, etc., except not the heart valve side effects).
March 11th, 2008 at 5:10 pm
[...] Samantha WilliamsnHThe furniture and investigating methodicalness assist seems to conceptualise that symbolize bacciferous accruement is predominantly a anxiety of call garner — and so they are “eat base training more” focused kinda than on try this anti-obesity med throught the … [...]
March 12th, 2008 at 3:40 pm
I am actually going to the Dr in 2 weeks to pre-screen for a clinical trial of this medication. I know the trial will last for 1 yr. I guess I will find out more about it then.
March 12th, 2008 at 3:56 pm
I go to this screening in a week. Can someone who has been taking it email me and tell me about how it makes them feel or the result. Tammy davisandtammy@aol.com
March 13th, 2008 at 9:17 am
Texas - where’s the trial? The Pennington in LA?
Tammy - I don’t think the company has posted the final results of the clinical trials, but see the interim results so far:
http://www.arenapharm.com/wt/page/lho.html
Here’s a copy of the company conference call and analysts questions (from Seeking Alpha):
http://seekingalpha.com/article/67893-arena-pharmaceuticals-q4-2007-earnings-call-transcript?source=side_bar_transcripts
Good luck — And thank you both for participating in clinical trials.
FDA -CDER: Get with it. No drug is perfect, but at least get some weight loss med out there with a the side effects in the label if need be. You already have the warnings on obesity: fat causes all sorts of things. So do you consider the benefit only weight loss or the avoidance of the consequences of obesity? What about using that as an end point?
Take the budget from the “eat less, exercise more” department and throw it at CDER’s group, hire more people, and get moving on this therapeutic area.
March 13th, 2008 at 1:54 pm
Hello…I am participating in this trial as well in Connecticut. I have been on the meds for 2 weeks and side effects have not been bad. The next day after the first dose I had an awful headache so I took Tylenol and it went away. Other than that I had had dry mouth and a little lightheadedness. Not too bad. I have also lost 5 pounds in two weeks. It seems to be helping.
March 13th, 2008 at 3:31 pm
Thank you for your comment Jennifer. Congrats on the 5 lbs in 2 weeks (!)
Thanks again for commenting, and thanks for participating in a clinical trial, that is very generous of you.
March 26th, 2008 at 9:51 am
I have taken my 3rd dose this morning (yesterday the AM dose was monitored at pennington). By now I’m 90% sure I’m on the placebo because of virtually no detectable side effects and it surely hasn’t curbed my appetite or cravings. Getting motivated to lose weight is tough, and I’ve been only feeling slightly motivated and answered the questionaire honestly. I’d kind of hoped I’d be on the ‘real’ drug to help with this lack of motivation. In 2005 (for 9 months)I took a 75mg of Effexor from depression when I lost a grandmother to cancer. I lost 30 lbs without trying (on effexor), because if I wasn’t hungry I didn’t care to eat. If my fiance wanted to go to wafflehouse at 9pm, I’d go with him to keep him company, but had 0 temptation and would drink a water or diet soda. (that side effect surprised both of us) It was easy to eat with health in mind. I remember how my brain felt different during that time and hoped for simular results with this trial. However I’ve decided prior to this that the dietician support and accountablity would be worth the effort and plan to continue even though I could be on a double dose of placebo. I’d like to connect with others on previous or current trials of lorcaserin. Thanks! leigh2anne@yahoo.com
March 26th, 2008 at 2:33 pm
Thanks LA — your Effexor experience brings into high relief the organic basis for eating motivation — I mean, self control and exercise play a role of course — but if a molecule can change your behavior so dramatically, why isn’t more work being done on that?
Sorry you haven’t had any effect, whether or not you are on placebo. My first thought — assuming you are on placebo — is that the data should look great for this trial, because of little placebo effect. Biostatisticians love no confounding placebo effects.
March 27th, 2008 at 8:28 pm
Thanks for your quick response Swivelchair. With your expertise on such things, is it possible that it may take more than 3 days (possible 10mg twice a day) to ‘feel’ anything? I asked the head of the study about the % of people on full placebos, and was told 44%. That’s pretty high. (1200 on placebo, 1200 on 10mg, and 800? on 20mg… or so). At the end of the 3rd day I’m 100% thinking I am on the placebo. But then I am comparing it to the 75mg of Effexor (though it did not kick in immediately).
My understanding is that this drug works on the hypothalmus part of the brain and creates feelings of satiety. diet pills don’t work for me since I don’t like the anxious feeling they create. Some of the effects from taking Effexor have stayed with me, such as being less shy in social situations… or as I tend to think that it gave me an opportunity to exercise a weak muscle in that department, and the positive social effects have stayed on. The satiety aspect of effexor did diminish over time, probably after 6 months (of 9 months). I do appreciate being part of the study even though I keep feeling I’m in the placebo group and also your comments and insight. Any thoughts?
March 28th, 2008 at 9:29 pm
Hi LA -
Probably the best source of information is going to be your clinical trial site managers (and docs) so please make sure you ask them as many questions as you have. They may not be able to answer all of them, but they can tell you what they don’t know.
I don’t know anything special about this drug or this clinical trial beyond what’s published, but years ago I heard a story about a person in another clinical trial for a different weight loss med. This person wrote to the company (who made the drug) thanking them profusely because of all the weight loss. Turns out the person was in the placebo group. Point: you just never know for sure until the data is unblinded.
Thanks again LA for being in the clinical trial. You don’t have to do this — and you may not see any benefit yourself. So it really is generous of you to participate.
April 16th, 2008 at 3:58 pm
Talked to the Dr here in Sacramento. Got an appt on the 17th for screening. Read a lot today on this. Looking forward to being part of the study. Just foud out my BMI is 44. It was 37 2 yrs ago. Ugggggg!
May 2nd, 2008 at 2:39 pm
Chef Russ, hope you get some weight loss, but you could get placebo.
Is it ethical at this point to do a placebo controlled? This should really be a cross over study at this point.
Having just listened to Morgan Stanley webcast (5/2/08), it seems like they should just put everyone on drug at this point — the valvulopathy and hypertension (the phen fen problems) would have been apparent by now, and the mode of action is known (5HT2c specific, not found on heart).
No one is going to see any really out there signal with these numbers. You need thousands and thousands to see if there is any kind of weird sub population one-off type result. At this point — where most pts have been 17-18 mos — why not put everyone on drug?
Sorry Chef Russ — I mean, here you are, watching your BMI going up, and we know that the drug causes weight loss which could rapidly prevent any harm from your rapid weight gain — I mean, at least preventing further weight gain.
Good luck to you and I hope your BMI can be reduced.
May 14th, 2008 at 2:28 pm
Im on day two of the trial… Im having some symptoms such as lightheadedness, dry mouth, headache, and a dizziness after the evening dose. Has anyone had any good results since starting??
May 14th, 2008 at 5:44 pm
Thanks for the comment eaa — I think the company said these were common side effects, that usually go away, but of course make sure you talk to the docs.
I think that the FDA needs to rethink the approval path with this one:
An extra year with obesity is very harmful — get this drug out with perhaps a “conditional” approval requiring post-market surveillance. As I said above, with 12-18 or more months of phIII data, with these numbers, no one is going to see any rare side effects.
Any unacceptable side effects would have been seen already — particularly since the mode of action is (a) known; and (b) fen-phen had something like 18 million scripts written — so any non-cardiac side effects would for sure have been uncovered and litigated along with the valvulopathy. Are you kidding? The litigation forensics on fen-phen were probably better than the FDA review to begin with. Maybe hire the Plaintiff’s experts to work at the FDA.
I thought I heard the company say (on the MS presentation) that most people on drug lost over 5% of body weight, and that no cardiac or psychiatric side effects have been observed at all. Even in placebo. (I could be wrong about that one). This is in thousands of pts after at least a year, maybe year and a half.
So why does the FDA want all this extra pre-approval data? Because they don’t see obesity as an exigent circumstance requiring immediate intervention? Because they see obesity as a moral failing and behavioral? The “truthiness” argument? Because they don’t think that irreversibly turning diabetic is that big a deal? Because they don’t think that an extra year or two of obesity-related costs in the health care budget is a problem?
Is the FDA protecting the last few years of lipitor? (My guess is that with weight loss there will be a lower need for anti-cholesterol meds).
Is the FDA playing to the diabetes drug industry?
Not that I’m trying to drum up conspiracy theories or anything.
May 18th, 2008 at 10:00 pm
I am supposed to go tomorrow morning, 5/19, for initial bloodwork for the study in Arizona and i’m having second thoughts. I lost 35 pounds on my own, gained back 10, and just feel stuck. What are your thoughts? I’m just not a drug person AT ALL. I hate to even take ibuprofen and won’t take tylenol.
May 19th, 2008 at 5:59 pm
Thanks for your comments alisa — Wow,losing 35 lbs on your own, that’s great.
You know, I can’t say about your situation. I do think that obesity, at some level, is an organic thing — there is an adiposity set point, and it’s different for different people. Plus, within the same person, it can change. It’s common to be heavier at 40 than you were 18. Why? Obviously your “metabolism” slows down, but why is that? Is it a character flaw? No, of course not.
Probably, obesity will be treated as a chronic condition, and drugs will be a part of it. If you’re not a drug person, good for you if you can lose significant amounts of weight on your own. But I don’t think there’s anything shameful at all in taking a med to lose weight/prevent weight gain.
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. People take up smoking to stay slim. So that’s actually a form of medication for weight loss (or preventing weight gain).
June 2nd, 2008 at 10:10 am
I have been in the study for 10 weeks now. I am 100% sure I am not on the placebo, because I took a decongestant “DM” without knowing it would interact with the medication and got serotonin poisoning (google that if want a scare!) I don’t blame the drug at all though, because I was told to call before taking anything over the counter so I’m just an idiot. I DEFINITELY know better now!! FYI – I have lost 21 pounds (10% of my body weight) in 10 weeks so I couldn’t be happier. I’m excited for the next 42 weeks because I wouldn’t mind being able to wear a single digit size by next summer!
June 2nd, 2008 at 1:07 pm
Thanks for the comment Marsha. In clinical trials you can’t live your life normally. I mean, normally, if you have a runny nose, you’d take a decongestant and not think much about. Not so if you’re in a study. So thank you for being in study, even though you didn’t know whether you’d get any benefit.
With your weight loss, I just don’t think the placebo effect with a pill is this great. With an injection, maybe.
From what I’ve seen of the data, it looks like there is a continuous, more or less linear, weight loss. So for all 42 weeks, let’s assume you’ll lose 2 lbs a week. (This could be a faulty premise if the drug just stops working, and you plateau at a particular weight, or start to regain weight. )
Let me do the math:
Marsha’s original weight (if 21 lbs is 10%) = 210
Marsha’s current weight: 210-21 = 189 lbs
Marsh’s weight at week 42 if 2 lbs a week for 42 weeks = 210 - 84 = 126 lbs
WOW.
On the adverse reaction with the OTC decongestant: Glad you are better . Serotonin syndrome apparently has been an issue for some time with the SSRI’s and even the decongestants should put the specific warning on the label as well as the SSRI’s. That’s the trouble with OTC drugs, there’s no gatekeeper, like the pharmacist, for drug interactions. It would be great if lorcaserin were OTC, since Alli(r) is, but that may require quite a bit more political backlash than the FDA is willing to put up with.
June 4th, 2008 at 9:35 pm
I had my echocardiogram done last week and go tomorrow for my first dosing. I’ll report my progress here, if you don’t mind. I’d love to find a forum where people in the study can get together and chat.
June 5th, 2008 at 1:33 pm
Thank you for your comment alisa. It’s great that you are participating in this clinical trial, very generous. You may get placebo, or drug — and it is a commitment for you, not knowing if you’ll even really benefit yourself.
The more I think about it, I’m surprised that there even is a placebo group in this clinical trial. I mean, which is more harmful, excess weight or this 5-HT2c agonist which is selective for brain receptors, not heart receptors?
The other thing is that there would be a huge reduction in diabetes with the introduction of a safe and efficacious weight loss med. To me, that would go a long way toward reducing the national health care bill. So, FDA, what gives?
One more thing alisa - As far as a forum, this post gets a pretty constant number of hits from people searching “lorcaserin” on Google — so there are probably others in the trials who are reading this.
But I really don’t know if there are any other weight loss forums having IM, chat, etc. which you can use (this blog doesn’t have that functionality).
So if anyone knows of any, you can past the link in the comments, and I’ll re-post as a blog entry optimized for Google, to send clinical trial participants to that site.
June 5th, 2008 at 9:50 pm
I started my first two doses today and I’m pretty sure I have the drug. I am less hungry, feel fuller with meals, and have a headache and am having dizziness. I’m eager to see if this continues or if I’ve somehow conjured up these symptoms to make myself believe i got Lorcaserin vs. the placebo.
The nutritionist said she’s confident I’ll meet my goal of 150 pounds with no problems at all, drug or no drug, as long as I keep up my activity level (training for a 5k, plus strength training) and keep my calorie intake limited to about 1500 daily. Weight today was 198.2
June 5th, 2008 at 10:39 pm
Thanks for the blow by blow description alisa.
Good luck with the 5K - plus, during the summer it’s hotter.
I wonder if the drug works better during the summer or with people who exercise because the heat tends to make the squalene in the brain more liquid and the receptors are less likely to be clogged up? (My totally speculative hypothesis of brain thermoregulation relating to weight loss).
June 6th, 2008 at 4:52 pm
Still headache this morning and dizziness as well. I had one bowl of weight control oatmeal and tried to eat an apple with it and was only able to eat 2 wedges. Amazing. I mean, most of the time I can exercise self control and stop eating when I should, but here I wanted to eat a healthy fruit and I couldn’t. I’ll fit it in at another time today.
June 6th, 2008 at 5:22 pm
Thanks alisa -
June 10th, 2008 at 5:00 pm
swivel, can you email me please
June 10th, 2008 at 11:13 pm
Devin my e mail is: swivelchair@neurologicalcorrelates.com if you would like to contact me == thanks
June 13th, 2008 at 9:09 am
So I have been on the drug for a complete 7 days and I’ve lost 2.5 pounds. My appetite is much less, sometimes so low it makes me a little apprehensive about continuing for a whole year. I have been able most days to eat 1500 calories, which is what the nutritionist gave me. There were a few days last week where I only got in around 1300.
Now, I am exercising almost every day. I have started eating more fruits and vegetables, though not as many as I should be! I just stocked the house yesterday with lots of fruit and carrots, so I’ll have food to grab and eat that’s healthy vs. eating something that’s boxed and in my pantry.
I’ll update here every few weeks, or you can check out my blog where I post about my weight and the drug as well.
June 13th, 2008 at 9:12 am
I typed my blog in wrong.
http://www.extrapounds.com/blog/littlealisa/index.php
that should hopefully work
June 16th, 2008 at 5:56 pm
Thanks alisa — I should note that the people who post on this are unknown to me, in fact, I have no idea if they’re really on the trial or not (no disrespect meant to anyone) — so if anyone is going to invest or go on the trial or make any other major decisions based on these posts, obviously I’m not recommending that.
June 16th, 2008 at 5:58 pm
And I just checked alisa’s web page, and it’s great — so you go alisa, and good luck.