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Weight Loss - Obesity

Michael Scally MD

Michael Scally MD

Doctor of Medicine
10+ Year Member
There are a number of weight loss drugs on the horizon. This is a very busy year for the FDA. The drugs under review for approval include Lorcaserin (Arena Pharmaceutical), Contrave (Orexigen Therapeutics), and Qnexa (VIVUS).

Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs that target G protein-coupled receptors, an important class of validated drug targets, in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases. Arena’s most advanced drug candidate, lorcaserin, is intended for weight management, including weight loss and maintenance of weight loss, and has completed a pivotal Phase 3 clinical trial program. Arena submitted a New Drug Application for lorcaserin to the FDA in December 2009. Arena Home : Arena Pharmaceuticals

Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the treatment of obesity. In addition to Contrave, the Company's second product, Empatic(TM), has completed Phase 2 clinical development. Each product candidate is designed to act on a specific group of neurons in the central nervous system with the goal of achieving appetite suppression and sustained weight loss, through combination therapeutic approaches. Orexigen Therapeutics.

VIVUS is a biopharmaceutical company developing innovative, next-generation therapies to address unmet needs in obesity, diabetes, obstructive sleep apnea and sexual health. The company’s lead product in clinical development, Qnexa®, has recently completed phase 3 clinical trials for the treatment of obesity; VIVUS filed an NDA with the U.S. FDA in December 2009. Vivus - Welcome


Arena Pharmaceuticals Receives PDUFA Date for Lorcaserin NDA
Arena Home : Arena Pharmaceuticals

FDA Assigns October 22, 2010, PDUFA Date -

SAN DIEGO, Feb. 26, 2010 /PRNewswire via COMTEX News Network/ -- Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) announced today that the US Food and Drug Administration (FDA) has assigned a Prescription Drug User Fee Act (PDUFA) date of October 22, 2010, for the review of the lorcaserin New Drug Application (NDA). The acceptance of the lorcaserin NDA filing confirms that the application is sufficiently complete to permit a substantive review, and the PDUFA date is the goal date for the FDA to complete its review of the NDA.

Lorcaserin is Arena's internally discovered and developed drug candidate for weight management, including weight loss and maintenance of weight loss, and is intended for obese patients or overweight patients with at least one weight-related co-morbid condition.

Jack Lief, Arena's President and Chief Executive Officer, stated, "With an October PDUFA date for the lorcaserin NDA, we are another step closer to our goal of improving the treatment of obesity. We believe that lorcaserin, if approved, will be well positioned as first-line therapy to help patients achieve sustainable weight loss in a well-tolerated manner."

The NDA is based on a data package from lorcaserin's development program that includes 18 clinical trials totaling 8,576 patients. The pivotal Phase 3 clinical trial program, BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) and BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management), evaluated nearly 7,200 patients treated for up to two years. In both trials, lorcaserin produced statistically significant weight loss with excellent safety and tolerability.

Phase 3 Program Overview

BLOOM and BLOSSOM comprise the pivotal Phase 3 program and are the basis of the lorcaserin NDA. These double-blind, randomized, placebo-controlled trials evaluated obese patients, Body Mass Index (BMI) 30 to 45, with or without co-morbid conditions and overweight patients, BMI 27 to 29.9, with at least one co-morbid condition, such as hypertension, cardiovascular diseases or glucose intolerance.

In addition to the pivotal program, Arena is evaluating lorcaserin in obese and overweight patients with type 2 diabetes in its BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial. Arena plans to file the results of BLOOM-DM as a supplement to the NDA.

About 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. Arena has patents that cover lorcaserin in the US and other jurisdictions, which in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity Arena might obtain.


Orexigen(R) Therapeutics Submits Contrave(R) New Drug Application to FDA for the Treatment of Obesity
Orexigen Therapeutics

SAN DIEGO, March 31, 2010 /PRNewswire via COMTEX/ --Orexigen(R) Therapeutics, Inc. (Nasdaq: OREX) today announced that the Company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Contrave(R) (naltrexone SR/bupropion SR), its investigational drug for the treatment of obesity. The NDA is based on a substantial body of evidence gathered through the Contrave Obesity Research (COR) clinical program, which included over 4,500 patients.

"The COR program was designed to address all the elements of the FDA guidance for weight loss and weight maintenance in patients with obesity. We believe that if approved, Contrave has the potential to serve the diverse needs of obese patients who currently have few treatment options," said Mike Narachi, President and CEO of Orexigen. "I want to extend my appreciation to the Orexigen team as well as the investigators and patients who participated in the COR program, which provided the high quality data supporting the submission."

Below are highlights from the COR program reported previously:

Contrave clearly met the FDA efficacy benchmark: 48% and 56% of patients on Contrave32 lost at least 5% of their body weight in COR-I and COR-II on an intent-to-treat basis, as compared to 16% and 18% of placebo patients who lost at least 5%, respectively (p<0.001).

Significant improvements were observed in cardiometabolic risk factors such as waist circumference, visceral fat, C-reactive protein, HDL cholesterol and triglycerides.

In the COR-Diabetes trial, patients with type 2 diabetes experienced significant weight loss and demonstrated meaningful reductions in HBA1c. Specifically, 45% of patients on Contrave32 lost at least 5% of their body weight on an intent-to-treat basis, compared to 19% of patients on placebo (p<0.001). Contrave patients also showed a 0.6% reduction in hemoglobin A1c (HbA1c) from baseline, compared to a 0.1% reduction in placebo (p<0.001).

Patients treated with Contrave demonstrated statistically significant improvement in quality of life, and in self reported exploratory measures of control of eating.

The safety profile of Contrave(R) was found to be consistent with the safety of the two approved active ingredients. The most common adverse reactions (greater than or equal to 5% and at least twice the incidence of placebo patients) were nausea, constipation, vomiting, dizziness and dry mouth. Serious events were reported infrequently and included events of cholecystitis (NB 0.2%, PBO <0.1%), seizure (NB <0.1%, PBO 0%), and major cardiovascular events (NB <0.1%, PBO <0.1%).

"Having achieved this important milestone, we can now focus for the remainder of 2010 on managing the review and approval process for Contrave with the FDA, preparing for the launch of Contrave, and partnership," said Mike Narachi.

About the COR Phase 3 Program

All four trials in the COR Phase 3 program (COR-I, COR-II, COR-BMOD and COR- Diabetes) were randomized, double-blind, placebo-controlled trials, including a four week titration period. The co-primary endpoints were the proportion of patients achieving at least 5% weight loss and percent change in body weight compared to placebo. These endpoints were calculated based on intent-to-treat (ITT) last observation carried forward (LOCF) analyses of all randomized patients who had at least one post-baseline observation while on study drug. Secondary endpoints included multiple measures of cardiometabolic risk, quality of life, and control of eating, as well as HbA1c in the COR-Diabetes trial.

About Contrave

Contrave is an investigational combination therapy believed to address both physiological and behavioral drivers of obesity. The two components of this combination therapy act in a complementary manner in the central nervous system. The central pathways targeted by this treatment are involved in controlling the balance of food intake and metabolism, and regulating reward-based eating behavior. In clinical trials Contrave was shown to help obese patients initiate and sustain significant weight loss, improve important markers of cardiometabolic risk and increase ability to control eating.


VIVUS Announces Date of FDA Advisory Committee Review of Qnexa(R) for the Treatment of Obesity
VIVUS, Inc. - VIVUS Announces Date of FDA Advisory Committee Review of Qnexa(R) for the Treatment of Obesity

Endocrinologic and Metabolic Drugs Advisory Committee Meeting Tentatively Scheduled for July 15, 2010

MOUNTAIN VIEW, Calif., March 26, 2010 /PRNewswire via COMTEX News Network/ -- VIVUS, Inc. (Nasdaq: VVUS) today announced that the Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) is tentatively scheduled to review the Company's New Drug Application (NDA) for Qnexa(R) for the treatment of obesity on July 15, 2010. VIVUS submitted its NDA on December 28, 2009 seeking approval to market Qnexa in the United States; on March 1, 2010, the FDA accepted the NDA filing for review. The target date for the FDA to complete its review of the Qnexa NDA is October 28, 2010.

"Review by the Advisory Committee represents a critical milestone for Qnexa and for VIVUS. We believe Qnexa, if approved, could become a treatment option for obese patients," stated Leland Wilson, chief executive officer of VIVUS. "We look forward to discussing the efficacy and safety data of Qnexa with the members of the Endocrinologic and Metabolic Drugs Advisory Committee."

The FDA will publish the final meeting date in the Federal Register FDA Federal Registers (FR) .
 
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Re: New Weight Loss Drugs

I respect the need for some people, the reserch, education gained and moneys invested and generated on these products.
I guess their prospective clients have already tried willpower and healthier lifestyle.
 
Re: New Weight Loss Drugs

FDA Reviewing Anti-Obesity Drugs.

The Wall Street Journal (4/13, Gryta - Regulators to Review New Drugs to Curb Appetite - WSJ.com) reports on three new anti-obesity drugs under FDA review: lorcaserin, Qnexa (phentermine/topiramate) and Contrave (bupropion SR/naltrexone SR). The Journal notes previous anti-obesity drugs and their controversy-stirring side-effects, and compares them to the newer drugs. An FDA spokesperson also said the agency is aware of the past issues and will evaluate the new drugs under the assumption that patients will likely take them indefinitely.
 
Re: New Weight Loss Drugs

Orexigen Revises Obesity Drug Data; Shares Drop
http://online.wsj.com/article/BT-CO-20100413-710316.html?mod=WSJ_latestheadlines

By Thomas Gryta

NEW YORK (Dow Jones)--Orexigen Therapeutics Inc. (OREX) adjusted some previously reported weight-loss data of its experimental obesity pill Contrave and plans to amend its recently filed approval application, but said the move isn't expected to affect the drug's review timeline.

The change, described as a math error, rattled investor confidence in Orexigen and comes as the small San Diego drug maker competes in a three-way race with Arena Pharmaceuticals Inc. (ARNA) and Vivus Inc. (VVUS) to develop a new obesity treatment, a potentially huge market.

"People are just reacting because they don't quite understand it," Chief Executive Michael Narachi said Tuesday as he visited with investors in New York. "We are making sure they understand how robust our evaluation process actually is."

Narachi said he still expects the Food and Drug Administration to accept the drug's application within 60 days of its filing, which was two weeks ago. Nonetheless, Orexigen shares--down nearly a third in 2010--fell below $5 for the first time in 10 months.

The error occurred because the year-long trial was designed to take patients that weren't responding to treatment at six months and see if they would respond to a higher dose. In the statistical analysis, those patients were essentially supposed to be counted twice but were mistakenly only counted once.

Narachi said the error was found when the company looked to see why data in the studies were different from each other. The change was first disclosed in a regulatory filing Tuesday.

As a result, the percentage of patients losing at least 5% and 10% of weight fell four to six percentage points from what had been previously reported. Still, the adjusted numbers continue to meet the FDA's benchmark for clinically significant weight loss, the company said.

Narachi said the company would file a "minor clinical amendment" to the application, but that "nothing is changing that is important to them."

Under FDA guidelines for clinical trials of obesity treatments, one of two goals must be met. A trial must show that at least 35% of the drug group lost at least 5% of body weight, but that group must be double the percentage of patients with similar weight loss on the placebo. Alternatively, a study can show that patients had an average weight loss that was at least five percentage points higher than the placebo group's loss.

Orexigen reported Tuesday that 50.5% of patients taking the drug lost at least 5% of their weight, but it had previously said 56.3% had met the benchmark. In the originally reported data, the company said that 17.1% of patients taking a placebo had lost at least 5% of their weight.

Of the three companies, Arena was first to file its application for lorcaserin in December. Vivus, developing Qnexa, filed for approval shortly after Arena and will face an FDA panel of outside experts in mid-July. The agency is scheduled to make a decision on both drugs in late-October.

Rodman & Renshaw analyst Elemer Piros said that while the companies all reported data around the same time, Orexigen has been lagging and this news won't help that perception.

"They are the late-comers; They probably won't have a decision on their drug until early 2011," Piros said.

Lazard Capital Markets analyst William Tanner said the news likely shook investor faith in Orexigen because it is a small company facing a complex FDA process and a "math error" could make people wonder if there are other problems lurking.

Regardless, he believes the fundamentals of the drug remain intact. "I don't think it is going to be a problem," said Tanner, who has a $12 price target on the stock. Orexigen shares recently were down 12% to $5.07.

All three companies are small and plan to enlist larger partners to help sell the drugs. Narachi said Tuesday that Orexigen's talks are "going great" and that the company is "laser-focused" on signing a deal before potential FDA approval.

The company is aiming to reach a deal to co-promote and co-develop the drug in the U.S., Narachi said, while offering options on both Contrave's overseas rights and for its other weight-loss drug in development, Empatic.

Orexigen is seeking commitments surrounding the launch of the drug, rather than focusing on large up-front payments.

"Milestones on approval and commitments prelaunch are more important to us," he said.
 
Re: New Weight Loss Drugs

FDA Panel Votes Down Qnexa

GAITHERSBURG, Md. -- An FDA advisory panel was divided over whether to recommend approval of the investigational weight-loss drug phentermine/topiramate (Qnexa).

The Endocrinology and Metabolic Drugs Advisory Committee voted 10-6 against recommending approval for the combination drug -- made by Vivus -- which was shown to be effective in helping obese and overweight patients lose an average of 6% to 10% of their body weight in the company's clinical trials.

Earlier, the vote was reported as 9-7 but one panelist later said he voted in "Yes" in error.

Continue Reading . . . Medical News: Panel Votes Down New Diet Drug - in Public Health & Policy, FDA General from MedPage Today
 
Weight-Loss/Obesity

Diets with High or Low Protein Content and Glycemic Index

The importance of the composition of a diet for the prevention and management of obesity is debated. Ad libitum consumption of low-fat diets results in short-term weight loss, and low-carbohydrate, high-protein, and high-fat diets (e.g., the Atkins diet) may result in substantial weight loss as compared with that achieved with other types of diets. However, the weight loss is generally not sustained beyond 1 year. Greater weight loss with low-carbohydrate diets may be ascribed to the satiating effects of high protein content, and there is increasing interest in the efficacy of diets that have a high protein content with a moderate carbohydrate and fat content.

A diet with a low glycemic index may have beneficial effects on body weight and body composition and on certain risk factors in overweight persons, but the effectiveness of ad libitum consumption of low-glycemic-index diets for weight control is controversial. The Diet, Obesity, and Genes (Diogenes) study is a pan-European, multicenter, randomized, dietary-intervention study designed to assess the efficacy of moderate-fat diets that vary in protein content and glycemic index for preventing weight regain and obesity-related risk factors after weight loss.


COMMENTARY: Ludwig DS, Ebbeling CB. Weight-Loss Maintenance - Mind over Matter? New England Journal of Medicine 2010;363(22):2159-61.


Larsen TM, Dalskov S-M, van Baak M, et al. Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance. New England Journal of Medicine 2010;363(22):2102-13.

BACKGROUND
Studies of weight-control diets that are high in protein or low in glycemic index have reached varied conclusions, probably owing to the fact that the studies had insufficient power.

METHODS
We enrolled overweight adults from eight European countries who had lost at least 8% of their initial body weight with a 3.3-MJ (800-kcal) low-calorie diet. Participants were randomly assigned, in a two-by-two factorial design, to one of five ad libitum diets to prevent weight regain over a 26-week period: a low-protein and low-glycemic-index diet, a low-protein and high-glycemic-index diet, a high-protein and low-glycemic-index diet, a high-protein and high-glycemic-index diet, or a control diet.

RESULTS
A total of 1209 adults were screened (mean age, 41 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 34), of whom 938 entered the low-calorie-diet phase of the study. A total of 773 participants who completed that phase were randomly assigned to one of the five maintenance diets; 548 completed the intervention (71%). Fewer participants in the high-protein and the low-glycemic-index groups than in the low-protein–high-glycemic-index group dropped out of the study (26.4% and 25.6%, respectively, vs. 37.4%; P=0.02 and P=0.01 for the respective comparisons). The mean initial weight loss with the low-calorie diet was 11.0 kg. In the analysis of participants who completed the study, only the low-protein–high-glycemic-index diet was associated with subsequent significant weight regain (1.67 kg; 95% confidence interval [CI], 0.48 to 2.87). In an intention-to-treat analysis, the weight regain was 0.93 kg less (95% CI, 0.31 to 1.55) in the groups assigned to a high-protein diet than in those assigned to a low-protein diet (P=0.003) and 0.95 kg less (95% CI, 0.33 to 1.57) in the groups assigned to a low-glycemic-index diet than in those assigned to a high-glycemic-index diet (P=0.003). The analysis involving participants who completed the intervention produced similar results. The groups did not differ significantly with respect to diet-related adverse events.

CONCLUSIONS
In this large European study, a modest increase in protein content and a modest reduction in the glycemic index led to an improvement in study completion and maintenance of weight loss.
 

Attachments

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Re: Weight-Loss

Obesity Surgery May Become Option for Many More
http://www.nytimes.com/2010/12/02/business/02obese.html

December 1, 2010
By ANDREW POLLACK

Weight-loss surgery, once a last resort for extremely overweight people, may soon become an option for those who are less heavy.

An advisory committee to the Food and Drug Administration will consider on Friday a request by Allergan, the pharmaceutical company, to significantly lower how obese someone must be to qualify for surgery using the company’s Lap-Band device, which restricts intake to the stomach.

On Wednesday, the F.D.A. acknowledged that a new study by the company showed that people in the proposed range of obesity who had the band experienced “statistically significant decreases in all measures of weight loss.”

If the agency approves the change, the number of Americans eligible for the Lap-Band operation could easily double, ensuring more sales for Allergan and probably more insurance coverage for such operations. But the proposed change, sought at a time when the obesity epidemic in the United States seems intractable, still leaves some people uneasy, in part because of side effects and failure rates. In addition, long-term weight reduction is hard to maintain.

“You’re talking about millions and millions of people who would meet these criteria,” said Dr. George Blackburn, associate director of the division of nutrition at Harvard Medical School. “Let’s make sure by the most rigorous research that this is safe and effective.”

A new generation of diet pills has failed to gain federal approval, limiting options for overweight Americans, and Allergan and other companies are betting that surgery will become more of a frontline option rather than a last resort.

“It would be kind of ironic if people have access to surgery and not medical therapies, where they can go from Weight Watchers to surgery and have nothing in-between,” said Dr. Louis J. Aronne, an obesity expert at Weill Cornell Medical College. “But it appears it may be the way it will be in the near future.”

Doctors have already started to operate on extremely heavy teenagers, not just adults. And some experts are recasting weight-loss procedures, known as bariatric surgery, as metabolic surgery, saying that it might be justified to treat diabetes, even in people who are barely obese or not obese. Gastric banding involves placing an inflatable silicone ring around the upper part of the stomach, which limits food consumption and makes one feel full faster.

Current guidelines say weight loss surgery is appropriate for people who have failed to lose weight through diet and exercise and have a body mass index, or B.M.I., of 40 and above, or 35 and above if a person has at least one serious health problem, like diabetes or high blood pressure, that is tied to obesity. Allergan wants to lower the threshold for the Lap-Band to a B.M.I. of 35 with no associated health problems and to 30 with such problems.

For instance, a person who is 5 feet 6 inches and has diabetes would have to weigh 216 pounds to qualify now. Under the proposed lower threshold, that person could weigh 30 pounds less, or 186 pounds.

Federal statistics suggest that nearly 20 percent of the adult population has a B.M.I. between 30 and 35, more than double the population above 35. Probably half or more of the people between 30 and 35 have some associated health condition.

Bariatric surgeons and some obesity experts say that surgery has proven to be the only way many people can lose a lot of weight and keep it off, and some cite a Swedish study suggesting that it prolonged lives. And, they say, the operations have become safer since the obesity thresholds were first set in 1991 in a meeting organized by the National Institutes of Health.

“The whole risk-benefit ratio is completely different than it was back then,” said Dr. Marc Bessler, chief of the division of minimally invasive and bariatric surgery at Columbia.

Banding is a less radical operation than the main alternative, the gastric bypass. It is also reversible and costs less — from $12,000 to more than $20,000, compared with $20,000 to more than $30,000 for a bypass. But banding also leads to a weight loss of about 20 percent on average, less than that of bypass.

Bypass has been the preferred operation in the United States, though Allergan executives said on a recent call with investors that banding now has about 50 percent market share. Within the banding market, Allergan’s Lap-Band has about 70 percent market share, according to the company, with the rest belonging to the Realize Band sold by Ethicon Endo-Surgery, a division ofJohnson & Johnson. Allergan’s band was approved in 2001.

To win approval of the lower threshold, Allergan sponsored a study in which 149 of these less obese people had the band implanted. About 80 percent of the participants achieved the goal of losing at least 30 percent of their excess weight, meaning the amount by which they were overweight, after one year. About 70 percent of patients experienced a side effect, like vomiting or pain. The F.D.A. indicated on Wednesday that it had questions about how meaningful the weight loss was and whether the results of the study would be applicable to people other than the white women who made up a large portion of the participants.

Some doctors are dropping the band, in part because some older studies suggest that up to a third of patients eventually have the band removed because of side effects or ineffective weight loss. While about one in 1,000 patients die within 30 days of surgery, a survey of members of the bariatric surgery society suggested that deaths occurring later are under-reported.

“Before they start putting the Lap-Band on patients who are 50 pounds overweight, the public has to be made aware of how dangerous this is,” said Stephanie Quatinetz, a New York lawyer whose daughter, Rebecca, died at age 27 in August 2009, two months after getting Lap-Band surgery.

One factor that is moving some experts to advocate surgery for lower body mass index levels is its effectiveness in resolving diabetes, hypertension and some other ills associated with obesity.

“There are dramatic metabolic effects that in many cases go well beyond the weight loss effects,” said Dr. Lee M. Kaplan, director of the weight center at Massachusetts General Hospital.

He said that while it was once thought that surgery worked mainly by mechanically restricting how much one can eat, it is becoming clear that gastric bypass, at least, has effects on hormones.

Some experts say body mass index does not adequately measure risk of health problems. For instance, Asians tend to get diabetes at a lower B.M.I. than whites.

“The B.M.I. limitation of 35/40, set in the period when the major objective of the operations was weight control, is no longer the primary appropriate guideline for the selection of candidates for bariatric surgery,” Dr. Walter J. Pories, a surgeon, and colleagues wrote in the journal Obesity earlier this year. Dr. Pories will be a member of the F.D.A. advisory committee on Friday.

Allergan, known mostly for its Botox product, which is approved for cosmetic and medical ailments like chronic migraines, wants to reverse slowing sales of the Lap-Band that the company attributes to the weak economy. In the first nine months of this year, sales of its obesity products, mostly Lap-Band, fell 4 percent, to $182.4 million.

Even if Allergan’s application is approved, perhaps a small fraction of the new candidates are likely to opt for surgery because many people avoid operations. “I don’t think it’s enough to overwhelm the health care system,” said Dr. Bruce Wolfe, president of American Society for Metabolic and Bariatric Surgery, whose executive council unanimously endorsed Allergan’s proposal. “That’s not happening with the people who are heavier and need it even more.”

The society says that 220,000 bariatric surgeries of all kinds were performed in the United States last year. That is more than twice as many as in 2003, but represents a small fraction of the potential pool.

Still, some less obese patients do want the surgery. Some online discussion boards tell of people who purposely gained weight to qualify, and some messages give advice to others on wearing hidden weights.

Rashida Brown says she wants surgery to help control her diabetes, high cholesterol and hypertension. But her insurer has refused to pay twice in the last few years. At the time, Ms. Brown, who is 5 feet 7 inches, weighed 195 to 220 pounds, putting her index below 35.

“I am willing to bet there are quite a few people in the same category as myself — just waiting,” said Ms. Brown, 53, a clinical social worker from Boston.

She may still have to wait, now that she weighs 175 pounds — putting her below even the proposed lower threshold.
 

Attachments

Re: New Weight Loss Drugs

CONTRAVE (NALTREXONE SR/BUPROPION SR COMBINATION) ADVISORY COMMITTEE BRIEFING DOCUMENT
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM235672.pdf


The Tuesday advisory meeting will be broadcast live by the FDA here, starting at 8:00 am ET.
http://collaboration.fda.gov/emdac/
 
Re: Weight-Loss

Weight Watchers Upends Its Points System
http://www.nytimes.com/2010/12/04/nyregion/04watchers.html

By ELISSA GOOTMAN
Published: December 3, 2010

Their world had been rocked, and the questions came fast and furious: A 31-year-old teacher from Midtown Manhattan who had barely touched a banana in six years wanted to know if she could really consume them with impunity. A small-business owner from TriBeCa wondered whether she was being nudged to part with that second (or third) glass of wine. And a woman with silky brown hair, on her way out the door after a Weight Watchers meeting in the basement of a Park Avenue South office building, had a particularly urgent need.

“I just have one question,” the woman said. “How much is a potato latke? I need to know for tonight.”

They and others had been searching for answers and grappling with their implications since Sunday, when Weight Watchers began unveiling its first major overhaul to its cultlike points system, prompting the 750,000 members who attend weekly meetings across the United States — and some one million online adherents — to rethink how they shop, cook and eat.

The new plan, company officials say, is based on scientific findings about how the body processes different foods. The biggest change: All fruits and most vegetables are point-free (or free of PointsPlus, as the new program is called). Processed foods, meanwhile, generally have higher point values, which roughly translates to: should be eaten less.

“If I lived in the Caribbean, maybe I’d be able to make goal,” said Susan J. Slotkis, 64, an interior designer at the Park Avenue South meeting on Wednesday. “The pineapple is great; all the fruits are fresh; you’re never tempted to drink juice.” In the new system, oranges are free, but eight ounces of orange juice cost three points.

When Weight Watchers introduced its points plan to Americans in 1997, it captivated a generation of women, propelling the company into a $1.4 billion empire. Weight Watchers points became a cultural touchstone: Restaurants like Applebee’s distributed special Weight Watchers menus; food companies like Healthy Choice listed points on their soup cans; and members bought Weight Watchers cookbooks, scales and points calculators. Members pay $12 to $15 a week to attend one of 20,000 weigh-ins and pep talks across the nation, or $65 to use the company’s Internet-monitoring program for three months.

Under the old points plan, all participants were given daily and weekly allowances of points, based on their particular bodies, and each food, from apples to pepperoni pizzas, was given a point value, based primarily on the number of calories it contained, with slight adjustments for fat (bad) and fiber (good).

“You could be holding an apple in one hand, which was two points, and you could be holding a 100-calorie snack pack of Oreos in the other hand, which was also two points,” David Kirchhoff, the president and chief executive of Weight Watchers International, said in a telephone interview.

Now, all of that has been upended. The new system allots points based on a complex formula that considers each item’s mix of protein, fiber, carbohydrates and fat. Making it more confusing, most people are now given more total allowed points — a kind of new math that requires recalculation of what had been ingrained.

Under the old system, for example, the average new member of Weight Watchers was allotted 22 daily points and an extra 35 weekly points. Now, the average new member is allotted 31 daily points and 49 weekly points. So while two potato latkes are now seven points instead of five, their portion of the total is about the same (too high). But a Burger King bacon double cheeseburger is still 12 points, making it slightly less objectionable under the new regime. And that little pack of Oreos? Up a point, to three.

“It’s a complete overhaul; it doesn’t get any bigger than this,” said Karen Miller-Kovach, the chief scientific officer for Weight Watchers International. “Fifteen years ago we said a calorie is a calorie is a calorie. If you ate 100 calories of butter or 100 calories of chicken, it was all the same. Now, we know that is not the case, in terms of how hard the body has to work to make that energy available. And even more important is that where that energy comes from affects feelings of hunger and fullness.”

Some people were drawn to the Weight Watchers point system by the idea that it seemed almost like an anti-diet: you could eat whatever you wanted, as long as you gauged the portion, counted the points and, if necessary, scrimped elsewhere. And while many members are lauding what one blogger described as a “Weight Watchers meets Michael Pollan,“ and celebrating the advent of the guilt-free fruit cup, others are pushing back.

“I don’t want to be forced to choose veggies. I do NOT like veggies or fruit,” one member wrote in an online discussion on the Weight Watchers Web site. “I feel like I am being forced to ‘diet,’ and that is what I DO NOT WANT.”

Kate A. Mack, 28, a high school English teacher in Allentown, Pa., questioned the timing of the shift, between Thanksgiving and New Year’s, long a challenging time for the weight-conscious (a half-cup of reduced-calorie egg nog, for the record, used to be three points and now is four, but remember, the allowed total has changed, too).

“If you’re going to a party, for instance, and don’t know what’s going to be served there,” Ms. Mack posited, “I don’t know what I can or can’t enjoy as a treat because I’m not entirely clear, without taking a second to go into the ladies’ room and go look up the point value on Weight Watchers mobile.”

Weight Watchers officials say the new plan has been in the works for three years and was tested in pilot programs throughout the country over the past year. Ms. Miller-Kovach said that pilot programs showed that, while members ate different foods, their caloric intake was roughly the same and they lost at least as much if not more. Weight Watchers members in Continental Europe have been using a version of PointsPlus for the past year, and those in Britain and Australia made the switch a few weeks ago.

Lauren Cohen, a svelte 64-year-old Weight Watchers group leader with dangly earrings, tall boots and the enthusiasm of a circus announcer, said that one points devotee was particularly agitated upon studying the new system this week. “I lost 64 pounds, I’m at goal, I love points. If it’s not broke, why fix it?” she recalled the man saying.

Her response: “The latest scientific research shows that this will be an even better way to maintain that.”

At the Park Avenue South meeting on Wednesday afternoon, Ms. Cohen warned her clients that, points or no points, even fruits and vegetables had their limits. One Weight Watchers credo, she said — to eat until satisfied, not stuffed — remained firmly in place.

“We’re not talking about running home with a wheelbarrow full of grapes from a vineyard,” she cautioned. Then she noted perhaps the most compelling piece of information, the one that made even the most banana-fearing members perk up.

“You see Jennifer Hudson on the cover of your weekly reader?” she said, gesturing to a picture of the slimmed-down starlet gracing the cover of the Weight Watchers weekly booklet. “Guess what plan she lost that weight on?”
 
Re: New Weight Loss Drugs

Panel Endorses Weight-Loss Drug
Medical News: Panel Endorses Weight-Loss Drug - in Primary Care, Obesity from MedPage Today

SILVER SPRING, Md. -- An FDA advisory committee has voted 13-7 that the modest weight-loss benefits of an investigational combination of naltrexone and bupropion (Contrave) outweigh the drug's blood pressure risk.

The bupropion naltrexone combo is the last in a trio of new weight-loss drugs that went before FDA panels this year, striving to be the latest treatment in the dwindling field of medications to fight obesity. The previous two drugs, phentermine/topiramate (Qnexa) and lorcaserin hydrochloride (Lorqess) were both rejected by the FDA after they fared poorly at advisory committee meetings.

But Tuesday's advisory committee ended very differently than the previous two.

Bupropion/naltrexone appeared to offer fewer side effects than the previous two drugs, although it also doesn't appear to work as well at helping obese patients lose weight.

The FDA will make an approval decision by Jan. 31. The agency does not have to follow the advice of its advisory committees, but it often does.

Orexigen, the company that makes naltrexone/bupropion in partnership with Takeda, is seeking approval for treatment of obesity and weight management in patients with a body mass index of 30 or above, or 27 or above and with one or more risk factors (e.g., diabetes, dyslipidemia, or hypertension).

Contrave combines an antidepressant and an anti-addiction drug, both of which have been used individually for 20 years -- naltrexone for opioid addiction and alcohol dependence and bupropion for depression and smoking cessation. However, little is known about combining the drugs for weight managment.

The Endocrine and Metabolic Drugs Advisory Committee reviewed results from Orexigen's four placebo-controlled, one-year, phase III clinical trials, which enrolled 3,200 obese patients with at least one comorbid condition, including diabetes and depression.

In all four trials, patients on the naltrexone/bupropion combination lost more weight than those in the placebo group (P<0.001), and more than 30% lost at least 5% of their body weight, which is one standard by which the FDA judges efficacy of weight-loss drugs.

In a pooled analysis, naltrexone/bupropion patients lost an average of 4.2% more weight than the placebo group (ranging from 3.3% to 4.8%). That falls short of the other FDA standard that after one year, the difference in mean weight loss between the active and control groups should be at least 5%.

In one trial where patients taking naltrexone/bupropion were compared with those undergoing a lifestyle modification program, the difference between the groups was even smaller, suggesting that diet and exercise can achieve similar results as naltrexone/bupropion.

"As far as efficacy goes, I think they made it by the hair of their chinny chin chin," said Melanie Coffin, the panel's patient representative.

In the FDA's assessment of the drug released last week, reviewers expressed concerns over several side effects -- a potential increased risk for dizziness, nausea, seizures, and high blood pressure among patients taking naltrexone/bupropion.

However, the panel was mostly just concerned with one side effect: The drug's effect on blood pressure.

In the trials, patients taking naltrexone/bupropion were more likely to have an increase in blood pressure and heart rate than placebo patients, an effect that was most pronounced during the first eight weeks of treatment.

However, patients taking naltrexone/bupropion who lost at least 5% of their body weight achieved lower blood pressure and heart rate compared with those who lost less weight. But the most impressive improvements in blood pressure and weight loss were seen among patients taking placebo who achieved more than a 5% weight loss, suggesting diet and exercise is the best option for obese patients to lower their blood pressure.

Panelists were concerned that a drug that is supposed to reduce obesity -- and hopefully other comorbidities along with it -- actually raised blood pressure instead.

"This is my biggest concern," said Lamont Weide, MD, PhD, chief of diabetes and endocrinology at Truman Medical Centers Diabetes Center in Kansas City, Mo. "That we are blunting all the good effects that we should see with weight loss."

The FDA reviewers concluded there wasn't enough data on the cardiovascular risks of the drug. The panel seemed to agree, but voted 11-8, with two panelists abstaining, that the company could submit new data after approval to show that the drug doesn't present major heart risks.

The panel's one neurologist, Michael Rogawski, MD, PhD, said he thought the panel downplayed the drug's seizure risk.

Two patients in the clinical trials experienced seizures after going on naltrexone/bupropion; no participants in the placebo group had seizures. About one in 1,000 patients who take the drug would be expected to have a seizure, the panelists said.

"They occur only in one out of 1,000, but still, the consequences of having a seizure could be catastrophic," said Rogawski, who ended up voting in favor of the drug.

There is currently just one anti-obesity drug on the market: Orlistat (Xenical, Alli), after Abbott, the maker of another drug sibutramine (Meridia) voluntarily agreed to remove it from the U.S. market in October because of increased risk of stroke and MI.

Several physicians and other healthcare professionals contacted by MedPage Today/ABC News were pleased with the panel's decision and said that doctors badly need a new drug to help patients battle obesity.

"It is nice to have a medication that can help those who are watching their diet and boosting activity lose the weight that thus far has been a slow process," said dietitian Connie Diekman, director of University Nutrition ?at Washington University in St Louis. "This is one more option in the tool chest to deal with the obesity issue."

"Finally!" said Robert F. Kushner, MD, professor of Medicine at Northwestern University Feinberg School of Medicine. "I fully endorse the panel's vote. The key will be to educate physicians on how to best prescribe the medication -- identify patients who will benefit from the medication and to accompany it with lifestyle and behavioral recommendations."

Paul L. Doering, a pharmacy professor at the University of Florida, said he doesn't "doubt for a minute that this drug will be wildly successful, at least at first," adding, "Time will ultimately tell if it is a good drug or not. In the meantime, I'm going to let somebody else be the first to take it."
 
Re: New Weight Loss Drugs

Michael Scally MD said:
Panel Endorses Weight-Loss Drug

An FDA advisory committee has voted 13-7 that the modest weight-loss benefits of an investigational combination of naltrexone and bupropion (Contrave) outweigh the drug's blood pressure risk.

The bupropion naltrexone combo is the last in a trio of new weight-loss drugs that went before FDA panels this year, striving to be the latest treatment in the dwindling field of medications to fight obesity. The previous two drugs, phentermine/topiramate (Qnexa) and lorcaserin hydrochloride (Lorqess) were both rejected by the FDA after they fared poorly at advisory committee meetings.
Click to expand...

Big pharma seems desparate for a weight loss drug. Contrave sucks as much as Alli/Xenical. Its use by bodybuilders (or lack of) should be a clue.
 
Re: Weight-Loss

Real Evidence for Diets That Are Just Imaginary
http://www.nytimes.com/2010/12/14/science/14tier.html

By JOHN TIERNEY
Published: December 13, 2010

Call it the Imagine Diet. You wouldn’t have to count calories, track food points or memorize rules. If, say, some alleged friend left a box of chocolate truffles in your home this holiday season, you would neither throw them away nor inhale them all. Instead, you would start eating imaginary chocolates.

You would give yourself a few seconds to imagine tasting and chewing one truffle. (If there’s a picture on the box, you could focus on it.) Then you would imagine eating another, and then another and another...until at last you could open the box of real chocolates without making a total pig of yourself. And then you could start on fantasies of other vices you wanted to eliminate.

So far, the Imagine Diet exists only in my imagination, as does any evidence of its efficacy. But there is some real evidence for the benefits of imaginary eating from experiments at Carnegie Mellon University reported in the current issue of Science. When people imagined themselves eating M & M’s or pieces of cheese, they became less likely to gorge themselves on the real thing.

This form of mental dieting — I think, therefore I’m full — sounds bizarrely counterintuitive, because we’re all familiar with the opposite phenomenon: thoughts of food that make us more eager to eat it.

Indeed, there’s a well-established phenomenon called sensitization, or sometimes the whetting effect: if you picture yourself eating chocolate, your desire for it increases, and such thoughts can cause you to literally salivate.

Similarly, imagining the sight or the smell of a cigarette will increase a smoker’s craving to light up. And when you actually smell or get a taste of something, that initial sensation can also increase your desire for it.

But eventually that effect is counterbalanced by another well-established phenomenon called habituation. Just as you adjust to bright lights and stop being bothered by bad smells, you get habituated to a food as you eat it.

“After you eat the first little cheeseburger at White Castle, your craving is probably greater than it was before you started your meal,” says Carey Morewedge, a psychologist at Carnegie Mellon and the lead author of the Science article. “But your craving is probably going to be lower by the time you start your eighth.”

At that point, you may stop ordering sliders and think you’ve lost your appetite for any food. But habituation is quite specific to the food you’re eating, as has been repeatedly demonstrated both by researchers and by pastry chefs. Restaurant patrons may feel they can’t eat another bite after going through the entree, but they suddenly feel peckish when the dessert cart arrives.

The experiments at Carnegie Mellon are the first to show that habituation to food can occur simply by thinking about eating, according to Dr. Morewedge and his colleagues Young Eun Huh and Joachim Vosgerau.

The habituation occurred as people imagined eating 30 M & M’s or 30 cubes of Kraft Cheddar, one at a time. They were shown photos of each M & M for three seconds, and each cube of cheese for five seconds.

The habituation effect didn’t occur when people imagined eating just three M & M’s or cubes of cheese. Nor did it occur when people imagined moving M & M’s one at a time into a bowl or doing other mental tasks, like feeding quarters into a laundry machine.

The effect required lots of mental eating, and it was specific to each food: the people who imagined eating chocolate didn’t lose their desire for cheese.

The imaginary eating didn’t make people feel any fuller, and it didn’t change their overall opinion of M & M’s or Kraft cheese cubes. They just didn’t feel like eating as much of it at that moment.

“Our desire for food has two components: liking and wanting,” Dr. Morewedge says. “We may very much like ice cream but not want to eat it for breakfast. Imagined consumption didn’t affect how much people in our experiments liked M & M’s, but did reduce how many they wanted to eat. Habituation is generally considered to be a motivational process.”

The importance of mind over stomach was demonstrated in 1998 in a striking experiment with two men whose mental functions were normal except for a severe form of amnesia. They were unable to remember an event for more than a minute. Their eating habits were studied on several days by researchers, led by Paul Rozin at the University of Pennsylvania, who created a rather extended lunch period.

After each man ate his lunch, the food was cleared. In a few minutes, a researcher appeared with an identical meal and announced, “Here’s lunch.” The men always ate up without any complaint about feeling full. Then, after the food was cleared and another few minutes passed, a third lunch was served, and the men always dug into it, too.

In fact, one of them stood up after his third lunch of the day and announced that he would “go for a walk and get a good meal.” Asked what he planned to eat, he replied, “Veal parmigiana” — the same food he had just had for lunch.

When the researchers tried the same experiment on a control group with normal memories, the people all refused a second lunch. They, unlike the men with amnesia, consistently felt less hungry after eating, but the sensation apparently wasn’t just coming from their stomachs, as the researchers concluded.

“Nonphysiological factors seem to be of major importance in the onset and cessation of normal eating,” Dr. Rozin and his colleagues wrote in Psychological Science. “The results suggest that one of the principal nonphysiological factors is memory for what has recently been eaten.”

Now it look as if even memories of imaginary foods can affect people’s desire to eat. Dr. Rozin says he is impressed with the new Carnegie Mellon study, and so is Leonard Epstein, an expert on habituation to food. Dr. Epstein, a psychologist at the State University at Buffalo, says the results raise intriguing questions for further research.

“Can you reproduce the effects over time, or do they only work once or twice?” Dr. Epstein said. “Obviously for this to be useful clinically, it is necessary to work repeatedly. Does it work for everyone, including obese people? Does it work for all foods, or just snack foods?”

Dr. Morewedge agrees that it’s too early to know how long-lived or useful this effect will be, or whether it will work at all with addictive substances like tobacco.

He hopes to study what happens when people imagine smoking cigarettes. But the results so far, he says, offer some hope of eventually diverting people to healthier diets.

For instance, if you had a bag of carrots and a bag of potato chips in your home, you might try mentally consuming the chips so that you’d be more inclined to reach for a real carrot. And then, assuming that worked, perhaps you could try habituating to other vices.

If you wanted to curb your lust for someone, would it help to envision an erotic encounter in exquisite detail? (In which case pornographers could call themselves providers of therapeutic materials.)

To cut your credit card bills, could you embark on imaginary shopping expeditions? Would fantasizing about goofing off help you stop procrastinating? If you imagined watching “Jersey Shore,” could you avoid the real show?

Dr. Morewedge doesn’t yet have answers, although he does allow that “habituation processes seems to be similar across a variety of modalities and stimuli.” Habituation is inhibited by variety, he says, so for it occur with activities other than eating, you’d presumably have to keep imagining the same act being performed in precisely the same way. And to habituate to a food, you’d have to do more than have vague thoughts about it.

“Our results suggest that you have to engage in the mental activity simulating actual consumption,” Dr. Morewedge says. “You can’t just imagine a whole steak or a whole bar of candy — you have to imagine eating a piece at a time.”

That was easy enough to do in the Carnegie Mellon experiments, which showed people pictures of each piece of food for a few seconds. But what if you want to try this at home? Clearly, there’s a need for an Imagine Diet smartphone app, or at least a book filled with lush illustrations of the planet’s most fattening foods.

No one has any plans for the Imagine Diet Book — not yet, anyway — but Dr. Morewedge and his colleagues have been joking about introducing a new format to the diet genre.

“It would be all pictures,” he says. “The first diet flip book.”


Morewedge CK, Huh YE, Vosgerau J. Thought for Food: Imagined Consumption Reduces Actual Consumption. Science 2010;330(6010):1530-3. Thought for Food: Imagined Consumption Reduces Actual Consumption | Science/AAAS

The consumption of a food typically leads to a decrease in its subsequent intake through habituation a decrease in one’s responsiveness to the food and motivation to obtain it. We demonstrated that habituation to a food item can occur even when its consumption is merely imagined. Five experiments showed that people who repeatedly imagined eating a food (such as cheese) many times subsequently consumed less of the imagined food than did people who repeatedly imagined eating that food fewer times, imagined eating a different food (such as candy), or did not imagine eating a food. They did so because they desired to eat it less, not because they considered it less palatable. These results suggest that mental representation alone can engender habituation to a stimulus.
 
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