Arena's New Obesity Drug: Safe, But Not Too Efficacious

After all that buildup, Arena's (ARNA) long-awaited two-year BLOOM trial results for its flagship obesity drug lorcaserin announced Monday morning were something of a wet squib. In short, yes lorcaserin seems to have cleared the approvability hurdles, and yes it has a nice safety profile, but none of this may matter much since it didn't cause dramatic weight loss on average.

The categorical endpoint looks pretty good. At twelve months, 47.5% of patients on lorcaserin lost at least 5% of their body weight -- double the amount of placebo patients that lost 5% of their body weight. The FDA requires 35% of patients and at least double the percentage of the placebo group to lose 5% of their body weight. In fact, about 23% of the lorcaserin patients lost 10% or more of their baseline weight, compared to 7.7% of the placebo group.

However, the mean weight loss endpoint fell short of expectations. Lorcaserin patients lost an average of just 5.8% of their body weight, or 3.6% placebo-adjusted. We had been hoping for something closer to 7% or 8% placebo-adjusted.

These results are even less appealing than those Orexigen (OREX) delivered in January for Contrave, and especially disappointing in light of the similar level of weight loss shown in a mere twelve weeks in the Phase 2b study. It sure seems as though most of the benefit of lorcaserin is shown in the first few months of treatment, although the company insisted on the analyst call that this was not the case.

As with Contrave, the results so far are consistent with a smaller population of strong responders and a larger population of weak responders.

ARNA shares plunged on the news to close down over 28% at $3.23 Monday. Some investors may have thrown in the towel on the obesity space, as competitors Vivus (VVUS) and OREX were down 2.5% and 4.5% respectively. This presents an attractive buying opportunity, since VVUS and OREX can only benefit from ARNA's stumble.

Disclosure: none

Comments

[PhillyDan:]

How convenient not to mention that Contrave's study had a strict diet and exercise regimen as part of their study. That the Vivus results were based on the higher dosage of their Onexa drug candidate. I would agree about VVUS but not OREX. In addition, don't roll ARNA under the bus yet! Had their study been done with a 20mg BID dosage, I'm willing to bet that they would have hit the 7 to 8% placebo-adjusted weight loss and still shown the same safety and tolerability profile as this study concluded. Check out Ed Sussman's blog on his experience with Lorcaserin in the Blossom trial that he participated in. Ed is a Medical Writer for MedPageToday.

Mar 31 01:25 PM

[Rafi Allos:]

The problem with your argument regarding 20mg BID dosing is that neither the BLOOM or BLOSSOM trials were conducted with such dosing and therefore the NDA that Arena will be submitting, which will be reliant upon those two trials as their pivotal trials, will be forced to seek approval for 10mg once or twice daily.

Neither Arena or the FDA will consider speculating that an increased dosage will lead to greater weight loss with a similar safety protocol and therefore there's no chance of approval of such a dosage without a Phase 3 trial investigating it. Arena simply cannot conduct such a trial with its current cash resources and it just does not seem feasible that it will seek a partnership with the intention of conducting such a trial.

In my opinion it would be too risky to speculate that going up to 20mg BID dosing will lead to a clinically significant increase in weight loss. It has been demonstrated time and time again, in particular with obesity drugs acting via a single pathway, that a simple increase in dosing will not increase the level at which plateau weight loss will be seen. It is more likely that the plateau will simply be reached quicker because of the complexity of human energy balance regulation.

Mar 31 01:51 PM

[PhillyDan:]

I don't disagree with your position. I know that they would have to do another Phase III study for a higher dosage of Lorca. Your point is well taken about whether a higher dose would lead to greater weight loss. I don't agee with you or other people making the argument about their current cash position. They have enough cash to get them through 2009 and into 2010, particularly with the Azimuth equity funding deal in place. Certainly, they would need additional financing but I still think they will have a partnership deal in place within the next 3 to 4 months.

Mar 31 04:00 PM

[Ruthanne Wi...:]

ARNA has been investigating lorcaserin for years. If at this late date they haven't gotten the dose with the best risk/return tradeoff into trials, then that doesn't speak any better for them than the 3.6% weight loss on this dose.

Mar 31 08:03 PM

[contrave st...:]

I'm nearly finished with my study experience with Contrave. I've lost over 25 pounds, 11% body weight, without any diet or exercise modification. The investigators I have seen at my check-ups are aware of this so, unless I'm an absolute anomoly, it can work without changing anything. I have gradually lost weight every month of the study. I have continued to eat normally (I had followed a fairly balanced plan prior) and I have a job where I'm on my feet nearly all day in my full-time job as well as being a three-quarter time student in college. Needless to say adding an advanced exercise regimen was out of the question due to only having 24 hours in a day. I think I would have lost more weight if I had possibly reduced my caloric intake and actually made it to a gym a few times a week. I am super-excited to see this come to the market and I will be one of the first in line because I'm proof that it can work when nothing else never has. I wish Orexigen the best of luck - well done!

Mar 31 10:09 PM

[PhillyDan:]

Thanks for this informative information from your experience with Contrave. I think there is room for more than one obesity drug in the market. I'm biased toward Arena since I'm a shareholder but I still would like to see both Orexigen and Vivus get their drugs approved since I believe each drug may work differently for different people and it will give people with overweight or obesity issues a choice of options.


On Mar 31 10:09 PM contrave study patient wrote:

> I'm nearly finished with my study experience with Contrave. I've
> lost over 25 pounds, 11% body weight, without any diet or exercise
> modification. The investigators I have seen at my check-ups are aware
> of this so, unless I'm an absolute anomoly, it can work without changing
> anything. I have gradually lost weight every month of the study.
> I have continued to eat normally (I had followed a fairly balanced
> plan prior) and I have a job where I'm on my feet nearly all day
> in my full-time job as well as being a three-quarter time student
> in college. Needless to say adding an advanced exercise regimen was
> out of the question due to only having 24 hours in a day. I think
> I would have lost more weight if I had possibly reduced my caloric
> intake and actually made it to a gym a few times a week. I am super-excited
> to see this come to the market and I will be one of the first in
> line because I'm proof that it can work when nothing else never has.
> I wish Orexigen the best of luck - well done!

Apr 01 04:36 PM

[contrave st...:]

I completely agree with you on this. I know that not every patient will have the same type of positive reaction that I did. Since every person has a different type of metabolism and lifestyle, the effects will be different for everyone. Does aspirin work exactly same way for everyone? Not likely, but it does have positive effects for a wide range of medical issues. As someone who works in different types of medical research at the University level, I have to say how much I appreciate the shareholders of the many companies that sponsor different types of studies. So, many thanks to you PhillyDan for helping support the next medical advances by investing in them. Disclaimer: I do not work for any of the companies listed here. My work is focused towards esophageal and breast cancer as well as diabetes research.


On Apr 01 04:36 PM PhillyDan wrote:

> Thanks for this informative information from your experience with
> Contrave. I think there is room for more than one obesity drug in
> the market. I'm biased toward Arena since I'm a shareholder but I
> still would like to see both Orexigen and Vivus get their drugs approved
> since I believe each drug may work differently for different people
> and it will give people with overweight or obesity issues a choice
> of options.

Apr 02 01:06 PM

[Grumann:]

Link to MedPage article: medpagetoday.com/P...

Ed Sussman lost 52 pounds (17%+) and eliminated several meds for diabetes during his 1 year trail. Assuming he was on Lorcaserin and not placebo, it appears that the drug, combined with dietary counseling and very light exercise can have significant results.

Apr 06 01:34 PM