Why Orexigen's Empatic News Is Good

A second set of Phase IIB results for Orexigen's (OREX) second weight-loss combination drug, Empatic, was released Wednesday. Two days later OREX and its two main competitors Arena Pharmaceuticals (ARNA) and Vivus Inc. (VVUS) are all down slightly.

Some wag said that VVUS went up immediately on the OREX Empatic news because Empatic prospects had been overhanging the share price of VVUS -- clearly a burst of creativity. No doubt the Booker Prize for fiction will be sent over to a certain brokerage firm in short order.

OREX's news was actually fine and bodes well for partnership. Mean weight loss at the high dose of Empatic was 6.1% placebo-adjusted over 24 weeks (ITT-LOCF). As expected, efficacy and safety data were good, reasonably comparable to earlier Phase IIb results and to OREX's flagship drug Contrave. Efficacy did not plateau at 24 weeks, and was better in combination than either of Empatic's constituent drugs alone.

OREX now envisions the entire obesity franchise, essentially its two late-stage drug candidates Contrave and Empatic, being offered in a single partnership and marketed in a complementary way, with Contrave as the first-line therapy. Empatic will likely carry a Class C pregnancy warning, as zonisamide now does, marking it as unsuitable for use by women who may become pregnant. To put this in perspective, women who weigh 200+ pounds, like many patients in these trials, are often counseled by doctors to lose weight before trying to become pregnant.

High-dose Empatic handily meets the FDA efficacy guidelines, and over a 53-week period both doses would likely meet both guidelines. The first efficacy guideline is that overall mean weight loss for patients taking the drug must be at least 5% over 52 weeks. The high dose of Empatic had 6.1% placebo-adjusted weight loss, as noted above. Low-dose patients lost 4.7%.

The second is a "categorical guideline." At least 35% of the patients on the drug, at least approximately twice placebo, must lose 5% or more of their body weight. The idea is to give a fighting chance to drugs that work like gangbusters but only for some subgroup. 60.4% of high-dose Empatic patients lost at least 5% of their starting weight, as did 46.9% of low-dose patients, compared to 14.7% of placebo.

I'll wrap up by quoting hilarious writer Jerod Poore of crazymeds.us on zomisamide, but for the full piece I'll have to send you to his main page and the link to "zonisamide" in the left-hand frame:

It hits pretty much every neurotransmitter there is in attempting to achieve neural homeostasis. This is the latest anticonvulsant out of Japan, and I'd bet folding money it was developed in response to all those kids seizing while watching the one episode of Pokemon we'll never see in this country.

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Comments

[Vitautas:]

"To put this in perspective, women who weigh 200+ pounds, like many patients in these trials, are often counseled by doctors to lose weight before trying to become pregnant."

That's also the counsel I give. The chances to be inseminted is much bigger for a women if she weighs less than 200+ pounds. I mean which man is going to.....

Oct 02 03:58 AM

[Ruthanne Wi...:]

@Vitautas: As a heavy chick myself, I can say, that wasn't maybe the most diplomatic way to put it, but yeah, that too. If you are 200+ lbs and in a stable relationship, your doc will likely tell you to slim down before trying to conceive, and if you are not in a stable relationship, you don't need a doc to tell you it will be easier to find one if you take off a few pounds. In most cases (male and female) weight loss is not a knowledge problem. BTW it is a good thing for guys that in general, given the right circumstances, many women will sleep with bald chubby guys. An observation, not a gripe.

Oct 03 11:49 AM

[PhillyDan:]

How many people were in this study? Not many is the answer. Until a full phase III study is done with well over 4000 people in it and heart testing is done, I won't be impressed. Arena with Lorcaserin has the safest effective drug candidate. NDA will be filed in early December and the FDA will approve it in October 2010. They have had over 7000+ patients in the Bloom and Blossom studies. Three years of testing for heart valve issues, a small number of AE's (A lot less than their competitors) and in most cases less than Placebo. The FDA wants a safe effective weight loss drug. Efficacy with a ton of AE's will not do the trick or studies with strict diets and exercise - did the diet and exercise lose the weight or the drug? Weight loss is not a speed game. You want weight loss to happen that a reasonable rate with few or no side effects and just as important, you want the weight to stay off.

Oct 03 02:23 PM

[Jerod Poore:]

Thanks for the shout-out. Turns out that zonisamide predates that particular episode of Pokeman, but not seizurogenic anime in general.

Like topiramate, one of the ingredients in Vivus' entry in the crazy weight-loss market, zonisamide is what we like to call a supermodel drug, in that it makes you skinny and stupid. Combining it with bupropion will probably make some people extra super happy about their imaginary weight loss. Zonisamide is also like topiramate in that it's a carbonic anhydrase inhibitor, which is why both drugs have kidney stones as a side effect. I love my topiramate and have learned to live with the kidney 'sand' and 'pebbles' I have at least twice a month. That may also have something to do with the aphasia, taste perversion and why they work for types of headaches and forms of epilepsy that no other drugs can help.

Contrave (CONTrol those cRAVings) is the more troubling drug. Both naloxone and bupropion can lower one's seizure threshold. People with eating disorders that involve self-induced vomiting are susceptible to seizures. Although that could be a feature, because you don't want to eat that much when you have a seizure hangover.

Topiramate was originally developed to help people with type 2 diabetes control their weight. It failed miserably due to neurological side effects so intense they investigated it for brain-related applications. Every few years Johnson & Johnson tries yet another clinical trial with the same results.

Oct 04 05:47 PM

[in4thelonghaul:]

Phase II means nothing in regards to competitors P-3 results. VVUS has by far the most effective candidate. Didn't almost 50% of ARNA's Contrave trial participants drop out?


Most informed patients will demand VVUS's Qnexa, and most will be willing to chance dry mouth, and possible tingling in the fingers to achieve the benefits of 15% weight loss which isn't gained back immediateely after they stop taking it. Seems likely that most insurance companies will favor Qnexa as well...why shell out so much money for a years worth of Lorcaserin, when Qnexa is 3 times more effective and has positive effects on blood pressure, blood sugar and triglycerides?

Almost certainly, physicians will first prescribe Qnexa, then Lorcaserin for those who decide they don't like the side effects. Only proiblem is Lorcaserin barely works, so many who get that will quit taking it after a couple o0f months and will go back to Qnexa, or might then try Contrave. But how many who take Contrave will be willing to endure nausea and headaches..not many.

VVUS's Qnexa will be a $ 3 billion blockbuster in the U.S. alone, and the clear winner in this race; then there is the potential for specific use for those with diabetes, and they do have a potential winner in their ED candidate...results soon to be out.

Oct 05 11:31 AM

[sastechie:]

The reality is: Qnexa is clearly more effective, and the side effects are tolerable and only last a few weeks. Read the phase 3 results and see how many subjects actually dropped out because they couldn't handle the tingling fingers. If a drug works well, people will put up with a few non-life threatening side effects to lose weight.

Oct 06 02:40 PM