The Great Weight Loss Drug Race

“The National Institutes of Health reported in 2007 that about 65% of U.S. adults are overweight or obese. A 2009 publication in Health Affairs estimated the annual medical burden of obesity in the U.S. to be $147 billion in 2008.”

If you’re living in the US and are at all aware of your surroundings, you’d know the weight loss market is a multibillion dollar machine that is only getting started. The financial implication of obesity and overweight americans trickles down in the form of disability costs, lost workers, and skyrocketing medical costs.

Cue pharmaceutical companies. We’ve had difficultyies getting a safe, effective weight loss medication on the market in the US for years. If you’re not old enough to remember Fen-Phen and similar drugs of the 1970s, the major concern was thepotentially fatal pulmonary hypertension and heart valve problems associated with use, which eventually led to their withdrawal from the market and billion dollar legal costs and damages in response to patients treated with the medicines.

There are currently three pharmaceutical companies in very close competition for FDA approval of a weight loss drug: Vivus Pharmaceuticals (VVUS), Arena Pharmaceuticals (ARNA), and Orexigen(OREX). Two of the companies, Vivus and Arena, have PDUFA dates in October, 2010. The two companies awaiting word in October each use one of the two chemical compounds in Phen-Fen as the basis for their present day drug, albeit theoretically safer and more clinically advanced weight loss formulations. The third pharmaceutical company, Orexigen, combines sustained release versions of popular antidepressant Wellbutrin and naltrexone, used for alcohol and opiate dependence.

More about the contenders:
Vivus Pharmaceuticals
The VVUS weight loss drug Qnexa has an FDA panel date of July 15th, 2010 and a PDUFA date of October 28th, 2010.“Qnexa contains drugs that are already FDA approved: it’s a low-dose combination of topiramate, an antiseizure medication that enhances feelings of fullness, and phentermine, the “Phen” part of Fen-Phen, which was not linked to heart valve defects.” Topamax is already prescribed for it’s off label use as a weight control drug. Qnexa is also being tested for Type 2 diabetes and sleep apnea. Additionally, Vivus also reported very good Phase 3 results from a new generation erectile dysfunction drug, making it an attractive buyout candidate, in my opinion. Once the FDA releases their panel notes in July and votes one way or another regarding approval on Qnexa at the panel itself, I think we'll see significant movement one way or another with the stock.

Qnexa has shown by far the greatest results for weight loss. In September, 2009, Vivus released Phase 3 results from the Qnexa clinical trials, Equip and Conquer:

Vivus, Inc. announced positive results from two final, phase 3 pivotal 56-week studies, EQUIP (OB-302) and CONQUER (OB-303), evaluating the safety and efficacy of Qnexa, an investigational drug, in more than 3,750 patients across 93 sites. The EQUIP and CONQUER studies met all primary endpoints by demonstrating statistically significant weight loss with all three doses of Qnexa, as compared to placebo. Patients taking Qnexa also achieved significant improvements in cardiovascular and metabolic risk factors including blood pressure, lipid levels, and type 2 diabetes. Highlights from the EQUIP and CONQUER studies include: Average weight loss of 14.7% (37 lbs) was achieved by patients treated with Qnexa for 56 weeks in the EQUIP study; Significant improvements in cardiovascular, metabolic and inflammatory risk factors among patients treated with Qnexa; FDA efficacy benchmarks for weight loss agents exceeded at all three doses of Qnexa tested in the clinical program; Completion rates up to 69% were significantly higher than placebo at all three doses of Qnexa, indicating favorable tolerability; and Favorable benefit/risk safety profile for Qnexa. The EQUIP study included 1,267 morbidly obese patients (1,050 females and 217 males) across 93 centers in the United States. The average baseline BMI of the study population was 42.1 kg/m(2) and baseline weight was 256 pounds. Patients had a 4-week dose titration period followed by 52 weeks of treatment.


Arena Pharmaceuticals
This company has a PDUFA date of October 22nd for Lorcaserin.
Lorcaserin is a novel single agent that represents the first in a new class of selective serotonin 2C receptor agonists. The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area involved in the control of appetite and metabolism. Stimulation of this receptor is strongly associated with feeding behavior and satiety. We have patents that cover lorcaserin in the U.S. and other jurisdictions, which in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity we might obtain.

“The Qnexa compound is more selective version of fenfluramine, better known as the “Fen” portion of the infamous blockbuster weight-loss drug combo Fen-Phen, which was pulled from the market. Lorcaserin is designed to avoid one of the serotonin receptors fenfluramine targeted- an activity that Arena believes was responsible for the heart valve defects Fen-Phen users experienced.”

After two Phase 3 trials, called Bloom and Blossom, Lorcaserin appears to have marginally met efficacy guidelines for the FDA governing weight loss criteria. Highlights from the trials:
* About two-thirds of patients achieved at least 5% weight loss and over one-third achieved at least 10% weight loss;
* On average, patients lost 17 to 18 pounds or about 8% of their weight;
* Secondary endpoints, including body composition, lipids, cardiovascular risk factors and glycemic parameters improved compared to placebo;
* Heart rate and blood pressure went down;
* Lorcaserin did not increase the risk of cardiac valvulopathy;
* Lorcaserin improved quality of life, and there was no signal for depression or suicidal ideation;
* The only adverse event that exceeded the placebo rate by 5% was generally mild or moderate, transient headache.

While Lorccaserin came in at breakeven in terms of weight loss efficacy, it’s safety profile is impressive, and doctors may err on the side of safety when prescribing to overweight/obese patients if Lorcaserin is approved. And the FDA may approve a safe, non controversial weight loss drug.

Orexigen Pharmaceuticals
Orexigen is developing two obesity drugs, Contrave and Empatic Contrave has completed Phase 3 trials, while Empatic is currently undergoing Phase 2 trials. Contrave submitted a new drug application (NDA_ to the FDA in March. In April, it revised Contrave clinical trial findings, showing the drug to be less effective than originally thought:
Reuters reported that Orexigen Therapeutics, Inc. said that fewer patients achieved key weight loss goals when taking its experimental obesity drug than originally reported. The Company said only 50.5% of patients who took the drug, Contrave, lost 5% or more of their body weight after 56 weeks, compared with a previously reported figure of 56.3%. Only 28.3% of patients lost 10% or more of body weight, compared with a previous figure of 32.9%. Contrave combines the antidepressant Wellbutrin, known generically as bupropion, and naltrexone, which is used to treat alcoholism. The Company recently filed for approval of the drug with the U.S. Food and Drug Administration. It is waiting to hear whether the agency deems the application complete and ready for review. The revision to the data is unlikely to affect the drug's timeline for approval.

Contrave, like Qnexa, is a combination of two drugs already on the market, bupropion
and naltrexone. Bupropion was approved for marketing in the United States in 1985 for depression and in 1997 for smoking cessation. Functionally, bupropion is thought to increase the level of dopamine activity at specific receptors in the brain, which appears to lead to a reduction in appetite and increase in energy metabolism. Orexigen’s developed a sustained-release formulation of the two active ingredients, Bupropion and Naltrexone.

Important Dates:
July 21st- FDA weight loss drug panel. Thus far, only Vivus has confirmed it will have it's drug Qnexa reviewed. It' not impossible that either or both Arena's Lorcaserin or Orexigen's Contrave could be added to the panel as well.
October 21st- Arena's Lorcaserin PDUFA date
October 28th- Vivus's Qnexa PDUFA date

Full Disclosure:
I already own VVUS June options and stock shares. I lovelovelove this company long term. That said, I'll be scaling back risk before the July meeting in case the FDA raises safety concerns, as I do with any panel or approval date.