Arena Eagerly Awaits Answer to $1 Billion Question: Does It Have a Big-Time Obesity Drug?

9/8/09Follow @xconomy

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when they released their first clinical trial results. Orexigen, based on my recent interview with CEO Mike Narachi, says it doesn’t plan to market its treatment to the masses who are a little bit overweight, but instead wants to pitch it to people who are more seriously obese, and need to lose weight to protect themselves from all the “co-morbidities” of obesity, like diabetes and high cholesterol.

Arena, by contrast, says its safety profile was so clean in the earlier study that it has confidence to market its product to the broader population of people who want to lose weight, Lief says. The drug showed an ability to be used in a broad patient population, help people lose weight fast, keep it off for a year, and improve important secondary measurements of cardiac and metabolic health, Behan says.

Importantly, the earlier study followed patients for two full years to see whether the Arena drug caused any damage to the heart, and didn’t show any serious concerns. This type of aggressive monitoring was required by the FDA, because Arena’s drug is designed to work in a similar way as Wyeth’s fen-phen combination did in the 1990s, before that drug was pulled off the market because it damaged heart valves. The Arena drug was designed to be more specific—to interact with an enzyme in the brain that controls feelings of fullness—without hitting a similar enzyme on the heart that led to the undoing of fen-phen.

Arena has heard the criticism from investors who say the safety looks fine, but the effectiveness isn’t that compelling. Lief took that one head-on when pressed. “We’re not talking about a wimpy drug from an efficacy perspective,” he says.

To buttress his case, he pointed to results from the earlier study that showed two-thirds of patients lost at least 5 percent of their body weight on lorcaserin, more than double the number who did that well in the placebo group. About one-third of patients on lorcaserin lost 10 percent of their body weight, which was triple the rate who achieved that threshold on a placebo, Lief says. Those readings of effectiveness meet one of the important criteria the FDA has said it wants to see from any new obesity drug.

What that shows is that individual patients can respond quite differently to the drug, and since obesity is related to so many genes, the company can’t say for sure which patients are likely to respond or why. When the data is taken all together, the average patient lost 5.8 percent of their body weight on lorcaserin, compared with 2.2 percent weight loss among those on placebo. The FDA likes to see at least 5 percentage points of improvement from an obesity drug, so Arena fell short on that score.

Lief dismissed that as unimportant, saying the FDA only needs to see a drug hit one of the two main effectiveness goals, not both. “No single drug has ever done that reliably,” he says.

Arena is clearly going to hang its hat on safety. The way I heard it, the message boils down to this: it won’t hurt, and it might help. “We’re positioning our drug to be the standard for broad usage,” Lief says. “Most people can benefit from losing some weight.”

And of course, physicians, the FDA, and insurers will look closely at all the secondary measurements of benefit to see if the drug is really worth it. This demanding set of measurements is part of why the drug development process takes a long time and costs so much. Arena obviously hopes these results will be bulletproof, because it’s hard to imagine a do-over for something with such high stakes.

“We’re going to have robust data from more than 7,000 patients. There were no shortcuts,” Lief says.

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  • http://www.liv.ac.uk/obesity Jason Halford

    The findings of this trial will be very interesting. However, a number of centrally acting drugs are under development, and a whole class of them – the endocannabinoids antagonists, failed in 2008. What is interesting is that all these drugs target similar appetite regulator centres in the brain. However, surprisingly it remains unclear how this or any of the drugs currently under development actually alters human appetite. If leading drug companies had measured the behavioural effects of the endocannabinoids in far more detail in early human trials they may have also uncovered the reported psychological side effects. In clinical trials, companies move increasingly quickly from determining potentially safe and effective doses in small groups of volunteers (phase 1) to examining weight loss and cardio-metabolic indicators in large scale patient studies (phase 2 and 3). Unfortunately, as currently conducted, neither type of clinical trial is sufficiently sensitive to detect drug-induced psychological effects (on mood or cognition).
    The onus is on regulatory authorities to demand that behavioural specificity of all drugs targeting human eating behaviour should be assessed in early phase clinical trials. This is particularly important for drugs acting on the Central Nervous System – CNS (anti-obesity or otherwise) where specific neuro-chemical systems are often involved in many differing psychological functions; in the case of rimonabant this relates to both the motivation to eat and experience of mood. When drugs are used to target human behaviour knowing exactly how they work, and how behaviourally specific they are, is very important. Determining this sufficiently in humans should precede any assessment of clinical efficacy. Until regulatory authorities appreciate this, then although this may sound like a cliché, history may well repeat itself, and not just for anti-obesity drugs but other medications targeting the brain to alter behaviour. Investors be warned.

    Dr Jason C.G. Halford Ph.D. C.Psychol. (Health)

    Reader in Appetite and Obesity
    University of Liverpool,

  • Jim Stevens

    Dr. Halford:

    Recommend you go to Arena’s website and review the presentation that Jack Lief gave at the BMO conference. In that presentation, you will see that Arena has had an “abuse” profile done on Lorcaserin and has come up with a clean bill of health on that front.

    So before you warn investors, do a bit more due diligence as this long time Arena investor has done and you will see that Lorcaserin indeed does have the safety and tolerability profile needed to be a very effective weight loss drug.

    Respectfully,

    Jim Stevens
    Carlsbad CA 92011
    Very Knowledgeable Investor

  • Jason

    Hi Jim.

    I have studied CNS anti-obesity drugs and 5-HT receptor agonists in particular for 20 years, and published plenty on them. It is actually a target I favour. I can send you copies of the papers if you would like. I also regularly check all the company websites. However, sorry to have upset you.

    Hopefully, the selectivity of the drug will make its side effect profile lower. However, as recent history demonstrates not all unwanted behaviour effects are detected in clinicals trial process. As an investors such issues are ones you should be aware of. This is more selective so it should be better but there is insufficient data.

    Yours diligantly.

    J

  • brigitte metzger

    bought orex because drug looks very promising….i only invest in things that i would use myself and it really doesnt have all the side effects that a lot of other drugs do or did…..especially when you have health factors that may stop you from using other drugs……
    sincerely yours
    B

  • Gloria Johnson

    Luke, thanks for another extremely informative article, this time on Arena. As an Arena shareholder, I’m anxiously awaiting the results of Blossom. The Bloom data released in March underwhelmed analysts but mainly due to their misunderstanding of what the FDA is looking for. You nailed it by stating that, “Those readings of effectiveness meet one of the important criteria the FDA has said it wants to see from any new obesity drug.” Lorcaserin is approvalable by the FDA. The market is big enough for more than one drug, but Arena is the one I’m betting on. The safety data for lorcaserin beats it’s competition and safety is even more important than total weight loss. Thanks again for the excellent coverage.

  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Gloria–thanks for the comment. I’m going to watch for the Phase III results from Vivus tomorrow morning to see how they might alter the competitive landscape for companies I cover in San Diego—Arena and Orexigen. If you or other investors have some immediate reaction to the Vivus data, please send it my way.

    Luke

  • Tony

    Nice article Mr. Timmerman. September will certainly be an interesting month for VVUS and ARNA. My money is on ARNA.