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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 18, 2009

Arena / Lorcaserin Update

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Posted by Derek

I wrote in March about lorcaserin, Arena Pharmaceutical's serotonin ligand for obesity. Their clinical data had come out, and things (at least to me) didn't look good. They didn't quite make the minimum threshold for efficacy, and the FDA isn't in a mood to take a flyer on on things that don't quite work.

Well, according to Ruthanne Roussel at Obesity Investor, the company looks like it could be running out of cash. So far, at any rate, no partner is appearing. Obesity has always been a tough area to work in, and this economic environment isn't making it any easier for the smaller companies to survive. Arena's done some interesting work over the years, and I'd hate to see them collapse. But it sure looks like a possible outcome at this point. . .

Update: note that not everyone agrees with my take here. On the other hand, others are even more harsh. . .we'll see what comes out in the end. And as always, since I've said nothing about having a position in Arena's stock, that means that I have none.

Comments (23) + TrackBacks (0) | Category: Business and Markets | Diabetes and Obesity


COMMENTS

1. hell to the chief on May 18, 2009 5:28 PM writes...

You are not the only one to resort to such lazy reporting with regard to the weight loss efficacy data for Lorcaserin. However, it is disappointing that after at least 2 people left comments on your previous article on this topic correcting you, you still went with the easy 'didn't quite make the minimum threshold for efficacy'.
There are 2 FDA defined efficacy criteria and this drug hit 1 of them. As it is currently an either/or for approval, your statement is therefore incorrect. In fact no approved obesity drug (alright there are very few approved so far) has ever achieved both in a 1 year trial.

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2. Anonymous on May 19, 2009 1:49 AM writes...

When you make ill-informed and inflammatory remarks such as this you lose much of your credibility -- even in areas where you are better versed. Please do your homework FIRST, and stop relying on posted comments from readers to correct your misstatements.

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3. Anonymous on May 19, 2009 5:08 AM writes...

Surely Derek has a point... If the mimimum thershold for efficacy comprises meeting two criteria, and it only hit one, then it's fair to say that it "didn't quite make the minimum threshold for efficacy" (i.e. meeting both crieria). Am I missing something? And, even if Derek is wrong, how does this make their financial situation any better than Derek suggested?

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4. Derek Lowe on May 19, 2009 7:19 AM writes...

Locaserin's not totally dead - there's still a possibility that it could be partnered off. But I fear that Arena doesn't have the time it needs to do that, especially in this environment. My opinion of the drug hasn't changed - it's not a bad compound, but I just don't see how it's good enough. I hope the company proves me wrong.

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5. petros on May 19, 2009 9:01 AM writes...

Derek

Your comments don't square with a number of others on these results. This article from Ed Susman (http://www.medpagetoday.com/PrimaryCare/Obesity/13506#rate), who was in one of the other phase III trials, is interesting since he mentions that he lost 52 lb, which makes him suspect he wasn't on placebo.

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6. hell to the chief on May 19, 2009 10:23 AM writes...

#3
AGAIN. The minimum criteria are to meet just 1 of the efficacy measures, both are not required. This was clearly done. I don't know how many times people need to say it before it sinks in. Yes the company needs cash, but the difference to future financing success will be potential investors/partners knowing they have an approvable drug or thinking (erroneously) like you, that they "didn't quite make the minimum threshold for efficacy".

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7. Anonymous on May 19, 2009 10:37 AM writes...

Derek seems like a bright guy, but in this case he is just wrong (he does not have a point).

The requirement is that the drug hit ONE of two benchmarks, NOT BOTH. There is a big difference in the English language between the words "or" and "and". In this case with the FDA (as with the vvus and orex drugs) the drug needs to meet just ONE of the two efficacy benchmarks -- it clearly did that, and so far it appears to be very safe and tolerable. This is not my opinion, these are facts publicly stated by the company.

So if Lorcaserin is safe and patients lose a meaningful amount of weight while on drug (and patients are willing to stay on the drug because it doesn’t have some of the nasty side-effects of the already approved treatments), why shouldn't it get approved?.

Money could be an issue, but money may eventually also be a problem for a big pharma company that passes on a potential blockbuster that they could have picked up relatively cheaply.

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8. Muruga on May 19, 2009 11:12 AM writes...

The FDA draft guidance on 'developing products for weight management' states the following
"In general, a product can be considered effective for weight management if after 1 year of treatment either of the following occurs:
* The difference in mean weight loss between the active-product and placebo-treated groups is at least 5 percent and the difference is statistically significant
* The proportion of subjects who lose greater than or equal to 5 percent of baseline body weight in the active-product group is at least 35 percent, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant"
As Locaserin has fulfilled one of the above two creteria, one can conclude that the clinical candidate has shown the minimum threshold for efficacy.

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9. CMCguy on May 19, 2009 11:39 AM writes...

#6 & #7 I have to jump in on Derek's side as he mentions the "mood" of FDA towards what approval of this might be. Because this looks like a case where having reached one of two possible successful outcomes it would "technically" be approvable however there is a practical consideration that since it did miss the other one there automatically going to be a higher burden to overcome. In recent years FDA has developed a apparent high powered biostatics dogma that does suggest "just over the line is not enough" and if have "negative" results they are evaluated against the positive data. Why the less "nasty-side effects" sounds promising such factors likewise do not often seem to get heavily weighted in decision process. Not dealing with Science Logic here but the mysterious realm of Regulatory which was always difficult to read before but in current flux makes predictability even more uncertain so Derek suggested nothing out of line.

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10. Alig on May 19, 2009 11:50 AM writes...

IF the drug is safe, which is a big if, and I never believe a company about that until all the clinical data is published, the most likely FDA action on this would be an approvalable letter. The FDA would want this drug studied in a much larger patient population to look for any CV risk (ie heart valve damage) over a longer timeframe. It is very rare these days for a drug to get approved without first having to do more safety studies. The FDA is scared stiff of another Vioxx.

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11. Fatboychemist on May 19, 2009 11:56 AM writes...

Um, the way I heard it, people only lost 10 more pounds than placebo, considering that people are supposed to take this stuff who need to lose a lot more than that, it's a dud. Word is from the inside that everyone knew that, but the "upper management" pushed it through anyway. Of course this is probably because their bonus was structured around them getting things through the clinic, as usual

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12. Anonymous on May 19, 2009 4:46 PM writes...

#10 (Alig).
The whole of the development program was set up to exclude CV risk at least in terms of valvulopathy which was one of the problems with phen-fen. 2 phase 3 trials with over 7000 patients combined is a pretty big data set (but of course the FDA could ask for more). It is also the main reason why the company has cash problems!

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13. Anonymous on May 19, 2009 9:57 PM writes...

The real risk is that the FDA decides to be Lucy.
Charley Brown runs up to kick the ball and they pull it away.
He lands on his back gasping.
They've done it before. More than once.

But ARNA did meet the published criteria and if they get it past Lucy, they will make a boat load of money.

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14. Anonymous on May 20, 2009 7:58 AM writes...

Hell to the chief - I assume you have some stock you'd like to cash in on...(?) Perhaps you should look for companies with drugs that meet BOTH efficacy criteria.

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15. biodummy on May 20, 2009 7:48 PM writes...

The trial came quite clean: the criteria they used (..The proportion of subjects who lose greater than or equal to 5 percent of baseline body weight in the active-product group is at least 35 percent, is approximately double the proportion in the placebo-treated group, and the difference between groups is statistically significant...) was defined prospectively rather than post factum - this was clear from the CC, so assuming the similar results from the rest of the trial program, it should be approvable efficiency wise. What bothers me is that via the analogy with fen-phen the docs would presumably want to use Lorcaserin as a combo with Phenthermine - at least that I'd think if I were a member of the advisory board. In fact, Lorcaserin as a monotreatment works the same or somewhat better than Fenfluramine (fen in fen-phen)! However, I never heard or read a concise explanation why even a small combo trial was not a part of Lorcaserin clinical study program - and pretending to be FDA I'd like to see this trial done before approval, at least for safety.

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16. Anonymous on May 20, 2009 11:39 PM writes...

#14 Anon:

Care to suggest such a company? Oh, wait...there are none. I don't think it would be a stretch to assume that you have no idea that NONE of the currently or historically available weight loss drugs met both criteria. Even rimonabant, which Wall Street was frothing at the mouth over before safety concerns doomed it, failed to meet the 5% placebo-adjusted criteria.

The 2 independent criteria exist for precisely this situation, where mean weight loss does not accurately convey the utility of the drug (i.e.clear responder and non-responder populations). Meeting both criteria is IRRELEVANT, because the two criteria are designed to account for different situations.

Crazy, huh! Maybe you, like Derek, should educate yourself before you spout ignorant comments about something you are clueless about. People like you make me, and other responsible web users, hate the internet.

Permalink to Comment

17. Anonymous on May 21, 2009 3:02 AM writes...

So at least we can assume that #16 Anon. does have some stock he's worried about...

As an ignorant web user, could someone please tell me why the FDA are holding up such an obviously useful and, infact, simply amazing drug....? Out of sheer awkwardness? At least we can assume that no one at the FDA has stock....

Permalink to Comment

18. Anonymous on May 22, 2009 1:02 AM writes...

Thanks #17 Anon, for making my point for me. Considering lorcaserin is currently undergoing Phase 3 trials, and considering Arena has not even filed an NDA yet, your implication that the FDA is ‘holding up’ anything makes it crystal clear how little you actually know about the situation you have decided to form an ‘opinion’ about and comment upon. Are you sure you aren’t thinking of a different company? Because the FDA has not been involved in the lorcaserin process in any significant way to this point (other than perhaps providing some guidance for clinical trial design).

And by the way, your transparent attempt to paint those of us who are simply arguing for the truth as biased ‘shareholders’ is not only a juvenile debate tactic, but is also, again, irrelevant. I could be Satan incarnate and it wouldn’t negate the fact that I, and others here, are simply stating the truth, which is that lorcaserin did indeed meet the efficacy endpoint. Tell me, what is your motivation that compels you to antagonize those of us who speak the truth? Do you not value truth?

As for Derek, it’s interesting that he has not retracted his statement. Instead, he’s left his inaccurate and harmful statement up for all to see like bird droppings on a hot windshield. Isn’t he supposed to be a scientist? I ask because the inability to admit mistake and the inflexibility to consider differing conclusions in the face of compelling, and in fact incontrovertible, evidence are not exactly desirable traits in one who supposedly empirically pursues truth in the name of science. It’s not really all that far off from data fudging, actually. His boss must be so proud.

Permalink to Comment

19. Anonymous on May 22, 2009 3:03 AM writes...

Ok #18 Anon, I'll stop winding you up know (to be honest, I do know nothing about the case).

Can I just ask a few questions, then I'll shut up...

1. Is there a problem with lorcaserin getting approval? If yes, what is it?

2. Are Arena running out of cash/about to go under? If so, why?

I look forward to your insightful response (and, if he is clearly off the mark on these points, Derek's retraction).

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20. Anonymous on May 22, 2009 3:32 AM writes...

Woahhh easy #18! I think your beloved Arena have far more important doubters than Dr Lowe (no offense Derek):

"Although the results technically satisfy the FDA requirements for approvability, we consider the weight loss benefits to be underwhelming at best," JPMorgan said in a research note.

"Needham analyst Alan Carr cut his rating on the tiny San Diego drugmaker to "hold" from "buy," saying the modest average weight loss may deter potential marketing partners and limit patient interest in the medicine."

Everyone is allowed their opinion just as much as you are. No need to get personal

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21. weirdo on May 22, 2009 10:11 AM writes...

Too many people view stocks as children and get emotionally attached. The lack of dispassionate analysis is an expected result.

No one can argue against the fact that the results of this Phase 3 study were disappointing ("not as good as one could have hoped", "could have been better" pick your phrase) -- not even the company would suggest such a thing. Heck, their response to the results was to lay off 130 of their employees.

I would note, however, that Lorca is/was meant to replace half of fen/phen, not the whole thing. So the bet should be on combo therapy, not Lorca as stand-alone. And those results are forthcoming, yes?

And, seriously, if you are long this stock, why do you care what Derek posts? If anyone, you should be OVERJOYED that the stock got hammered. Dancing in the streets OVERJOYED. It provides you with a tremendous buying opportunity to add to your position before the big hockeystick-like run-up to $100.

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22. Anonymous on May 22, 2009 11:51 PM writes...

1. nothing in particular...Derek believes the efficacy is an issue but as I stated before, it is in line with all other available drugs but with better safety. Again, rimonabant is a great reference point as well, as its efficacy was not considered an issue by analysts but it was killed by CB-related side effects...lorcaserin's efficacy is just about equivalent but is suddenly now unjustifiably (IMO) in the doghouse in terms of efficacy

2)Arena is not about to go under. Yes, cash is dwindling but there are numerous potential avenues for further cash (credit from Azimuth, real estate, potential partners not just for lorcaserin but other promising targets). So while cash is an issue, it is premature to consider it a killer

Thanks for admitting to 'winding me up'. I'm all for others' opinions as long as they are grounded in fact. I am most definitely NOT ok with standing by when untruths are touted as truth.

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23. Anonymous on May 23, 2009 8:47 AM writes...

People who may have over-invested in a company and are getting nervous apparently believe that making anonymous comments on message boards will actually influence the scientific data and help their stock value. You can be as positive and upbeat as you want, attack anyone who disagrees with you, and, you know what, the market is not going to care.

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