Low-Dosage Xenical (alli) Approved for Over-The-Counter Use (February 2007)

GlaxoSmithKline Consumer Healthcare announced Feb. 11th that the US Food and Drug Administration approved the weight-loss product orlistat 60 mg capsules for over-the-counter (OTC) use in the United States. GSK Consumer Healthcare will market OTC orlistat under the brand name alli ™ (pronounced AL-eye).  Approved for use by overweight adults in conjunction with a reduced-calorie, low-fat diet, alli helps people lose 50% more weight than with diet alone.  alli is the only FDA-approved weight loss product available to consumers without a prescription, and it is the first clinically-proven over-the-counter product to be combined with a comprehensive support program. alli is expected to be available in stores nationwide by summer 2007. This approval marks the start of an educational program that includes a series of resources online at myalli.com.

GSK Consumer Healthcare selected alli as the brand name because it conveys the concept of partnership with consumers in their weight-loss efforts.  With alli, consumers have access to an individually tailored online action plan that provides support and the necessary tools to help them lose 50% more weight than with diet alone, says GlaxoSmithKline.

Unlike other products on store shelves, alli is a proven medicine with a comprehensive support program. To help consumers get off to a successful start, the alli package will include Welcome and Companion Guides, a Guide to Healthy Eating, a Daily Journal, a Calorie and Fat Counter, Quick Fact Cards, and free access to an individualized online action plan at:  www.myalli.com.

"With alli , we're excited to offer a revolutionary approach to weight loss," says Steven L. Burton, Vice President, Weight Control, GlaxoSmithKline Consumer Healthcare. " alli is more than a pill - it's a comprehensive program that works in conjunction with a sensible diet to increase weight loss. Because weight loss doesn't happen overnight, we're starting to educate consumers now about the importance of realistic expectations, gradual weight loss and lifestyle changes. That's the way to see results, and with alli, we know they can do it."

GSK Consumer Healthcare is gearing up production to have the product ready for shipment and in stores by the summer. The company is using this period to build awareness and understanding about the product and its intended user.  It's for the committed consumer who can follow a reduced-calorie, low-fat diet. alli is indicated for weight loss in overweight adults 18 years and older when used along with a reduced-calorie, low-fat diet. The recommended dose of alli is one 60 mg capsule three times a day with meals containing fat.

Taken at meal-time, alli works by blocking about 25% of the fat in the food a person eats. Because of the way it works, alli must be used in conjunction with a reduced-calorie, low-fat diet containing about 15 grams of fat per meal.

Acomplia (Rimonabant) - U.S. Approval Status

The latest new prescription anti-obesity drug that is closest to U.S. market launch is Rimonabant, brand name Acomplia. This is a drug under development by Sanofi-Aventis (formerly Sanofi-Synthlabo). Acomplia is a selective CB1 endocannabinoid receptor antagonist indicted for the treatment of obesity. The drug has progressed to phase III development. It works by blocking endogenous cannabinoid binding to neuronal CB1 receptors. Other drug companies are developing their own compounds that work on the same brain receptors, but Sanofi-Aventis is the first to perform clinical trials.

It is the only endocannabinoid receptor antagonist in clinical development and this offers a unique therapeutic approach to appetite control and weight reduction. The drug also has potential as a treatment for smoking cessation.

Acomplia (Rimonabant), stalled at the U.S. Food and Drug Administration for more than a year, now will not be acted on at least until the end of July, Sanofi-Aventis announced on Febriuary 12, 2007

The French pharmaceutical company said that in an effort to improve chances that Acomplia will be approved for sale in the United States, it has submitted new data from its SERENADE study to the FDA showing that the drug also improves blood sugar control in patients with Type 2 diabetes.

No reason for the new delay was given by Sanofi or the FDA, but few observers believe the agency will act on Acomplia until its Endocrinologic and Metabolic drugs Advisory Committee weighs in on the issue of the drug’s side effects.

The advisory committee’s next meeting is tentatively scheduled for June 13 and 14, 2007.

Sanofi has long refused to provide any information about what sort of data the FDA has been seeking, though many analysts have speculated that it involves concerns about Acomplia’s side effects, which include depression.   Clinical trials had a relatively high patient dropout rate due to such side effects as dizziness, nauseam anxiety and depressed feelings.

Acomplia (Rimonabant), which remains a considerable distance away from approval by the FDA, has nevertheless edged a step closer to eager American customers with the news that it can now be bought in some pharmacies across the Mexican border.

Mexican prices for the diet drug reportedly are in the $100 range for 28 pills, making purchases in Mexican border towns, if a visitor either lives just across the border or is in Mexico on holiday, a less expensive option than purchasing the diet pills by mail order from Europe.

The FDA has repeatedly warned that many “brand-name” drugs purchased in Mexican border pharmacies (even those in perfect packaging) have been found to be counterfeit. Surprisingly low prices for drugs should be treated with particular suspicion.

The importation of “unapproved new drugs” – any drugs that have not received FDA approval, as is the case with Acomplia, is prohibited.    

In December 2005, a probe by the FDA found that the majority of prescription drugs ordered from web sites believed to be Canadian pharmacies originate from out side Canada. This finding came from an inspection of packages ordered by U.S. consumers, that came into JFK, Miami, and Los Angeles international airports. Out of nearly 4,000 shipments, 43% were ordered from "Canadian" Internet pharmacies and were represented as being of Canadian origin. Of the 1,700 suspicious packages, 85% of the drugs weren't manufactured in Canada and in fact came from 27 different countries. According to the FDA: "This operation suggests that drugs ordered from so-called Canadian Internet sites are not drugs of known safety and efficacy."

In addition to having been falsely promoted, many of the drugs weren't adequately labeled in English to help assure safe and effective usage.

Obesity costs America a staggering $100+ billion in health care costs and weight-loss products and programs, according to the U.S. Surgeon General. And as the rate of obesity in America is growing, there has been a fundamental shift in how obesity is viewed--as a disease rather than simply poor lifestyle habits.

"Obesity used to be viewed as a lack of willpower in a patient... It was not viewed as a medical problem. Today I think it is.", according to Douglas Greene at the University of Michigan. The bottom line is that a growing consensus holds that the traditional approach to weight-loss - diet and exercise - is futile for the majority of people.

We may be entering a new era of "lifestyle drugs" aimed at tackling such things as: hair loss, aging skin, weight gain—all the lifestyle issues of the baby boomers. As a recent Business Week article pointed out, "At a time when people lay out $20 or $30 a month on cable TV, it seems likely they’ll pay as much for a lifestyle drug."… "Hundreds of millions of dollars are being poured into efforts to discover safe and effective treatments for obesity, anxiety, memory loss, depression, incontinence, and arthritis."

However, there is no guarantee that the new drugs being developed will work long-term, and the FDA is likely to set high standards for approval. Questions remain as to how long studies must last and what amount of weight loss is optimal. Some FDA advisers want the drugs to also reduce the incidence of such obesity-related problems as diabetes or hypertension. And, because obesity isn’t directly life-threatening like AIDS or cancer, the risk of taking a drug over the long term is weighed carefully against the benefit of weight loss.

In 1997, bariatricians and other doctors were swamped with demand from their patients for prescription diet medications. The ranks of the American Society of Bariatric Physicians (ASBP) tripled to record levels and prescriptions for the two drugs approved for use, the "fen/phen" combination, skyrocketed. "Fen/phen" refers to the combination of: Fenfluramine, and Phentermine.

Phentermine is sold under 18 different brand names. The most commonly used are: Phentermine, Fastin, Pondimin, Adipex-P, and Ionamin. Others include: Anorexin, Bacarate, Bontril, Melfiat, Obenil, Plegine, Preludin, Pre-State, Sanorex, Statobex, Tenuate, Tepanil, Trimtabs, and Voranil.

Dexfenfluramine, (brand name Redux) made by Interneuron Pharmaceuticals Inc. in Lexington, MA, already was available in 65 countries.

Finding a profitable drug will require some luck. Researchers believe obesity results from a number of genetic and environmental factors. The hope is that doctors will one day have a variety of drugs to customize treatment of overweight persons.

Many doctors believed that these newly popular drugs, used in combination, would work better than any diet drugs still on the market (i.e. dietylpropion and mazindol), and that it represents a long-overdue change in the way the medical profession views weight control. Many doctors believe that medication may be the best way to correct a serotonin imbalance. Others, however, think it just exposes patients to more potential side effects, or that overuse or abuse may become a problem.

These medications generally work best when combined with exercise programs, and are found to be least effective when overeating takes place mainly for psychological reasons (depression, stress, loneliness).

Some obesity experts fear the Redux scare will cause long-term damage to the notion of treating obesity with drugs. Also potentially hurt are the prospects of new diet drugs, working differently, that await FDA approval or are in late stage clinical trials, and in the development of new agents." Personnel at the American Society of Bariatric Physicians (obesity specialist physicians) are afraid the problems are going to cause a setback in the approval of new agents.

It appears that the FDA may be moving toward easier approval of obesity drugs. A draft proposal indicates that human trials required for the drugs’ approval may be shorter and won’t have to show as many benefits as earlier-proposed guidelines. If the FDA approves the changes, a new generation of anti-obesity prescription drugs are more likely to reach the market over the next several years. Before dexfenfluramine, the agency had not approved one since the 1970s.

Pharmaceutical firms say that the new anti-obesity drugs should only be used along with strict programs of exercise and diet. However, we all saw how fast Redux caught fire with dieters who merely wanted to lose a few cosmetic pounds. The discovery of a flawed fat gene is no excuse to junk the treadmill and toss out the calorie counters. That was the unanimous message from nutritionists, fitness experts and diet coaches.

It would be simplistic to say that currently-used diet medications, and future ones under development through the early part of this century, will render obsolete commercial weight loss programs and other commonly used over-the-counter do-it-yourself products. Not everyone will be able to afford the ongoing costs. Not everyone will be candidates for such treatment. Some of the therapies may include taking injections, a turn-off for the squeamish. Others may prefer a more "natural" approach to weight management - proper diet and more exercise.

The role of many physicians in weight management is also suspect. Traditionally, doctors have not had the time to counsel their patients in depth about smoking cessation or losing weight. And, the psychological/emotional issues related to obesity are crucial. Will doctors that don’t specialize in treating obesity (i.e. general practitioners, etc.), increasingly squeezed by managed care and growing caseloads under HMOs, have the time to motivate, cajole, counsel and offer the peer support that commercial weight loss organizations such as Weight Watchers, Jenny Craig, or eDiets.com offer? BestDietForMe.com/Marketdata analysts don't think so.

Prescribing diet drugs can become a "cash cow" for many doctors whose incomes have been squeezed by managed care. The "diet industry" sometimes also attracts doctors with troubled pasts. Penalties for dispensing bad weight loss counseling are rare and minor. They may keep physicians out of insurance plans, but that doesn’t matter much in weight loss and other optional medical services, since insurance rarely covers diet plans and patients pay their doctors "out-of-pocket".

Preliminary results from early studies on the use of daily injections of genetically engineered leptin are reporting weight loss among some genetically obese subjects. Higher doses may be needed for higher weights. The most common side effects were pain at the injection site and headache. There appear to be no significant adverse effects on major organs, including the heart, liver, kidney, central nervous system, or gastrointestinal tract. It also does not appear to affect insulin levels, a previous concern.

According to the Wall Street Journal, Genomics-based obesity drugs are being tested in human trials. After years of analyzing the human genome, scientists at Millennium Pharmaceuticals say they have finally found a gem; an obesity drug that works by changing metabolism.

Traditionally, obesity drugs have been appetite suppressants, which often come with severe side effects. The new drug, co-developed with Abbott Laboratories of North Chicago, is part of a new class of medications that seek to alter metabolism.

Known by the name MLN4760, the drug is based on the discovery of a gene that provides instructions for the production of an enzyme that scientists believe helps prompt the body to store fat. The drug doesn’t act directly on the gene, but rather inhibits the enzyme’s action- theoretically prompting the body to burn fat, rather than store it. It is still too early to tell if the drug will be a success. Most early-stage drugs in fact fail.

Sibutramine (Meridia) keeps two important brain chemicals -- serotonin and norepinephrine -- in balance, which helps to increase metabolism. It causes a feeling of fullness and increases energy levels. Studies indicate that sibutramine helps with weight loss and helps maintain it. Patients who discontinue the drug, however, report significant weight gain afterward. Some studies also report improved cholesterol and other lipid levels with the use of this drug.

Common side effects include dry mouth, constipation, and insomnia. Also of concern are reports of increases in heart rate and blood pressure, although on the positive side, several studies reported significant improvements in cholesterol. Experts believe that sibutramine is probably safe, but the long-term effects are still unknown.

Orlistat (Xenical) can help about one third of obese patients with modest weight loss, and can assist in long term maintenance of weight loss. It reduces the body's absorption of fat from foods, reducing weight and cholesterol. Orlistat blocks the action of lipase, an enzyme in the intestine that breaks down fat.

Studies have found that at the end of the first year Orlistat users achieve an average of 5% to 10% drop in body weight. Studies are also reporting that the drug may delay or prevent the onset of type 2 diabetes, improve cholesterol levels regardless of weight loss, and reduce blood pressure. It should be noted that some people who take this drug experience an increase in blood pressure. The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients.

Thousands of new U.S. users flock to the drug each month. But discouraged by the cost, lack of overnight results, and the occasional nasty side effects—diarrhea after a high-fat meal, many drop it more quickly than the average diet. As a result, the Swiss company has had to launch costly marketing and hand-holding efforts, and even offers months of free pills to get patients to stay on the drug.

Roche installed a phone counseling-support program called Xenicare several years ago, which may/may not be operating today. Only 15% of Xenical users were enrolled in that support program. Fewer than half of Xenical patients got refills beyond a month of two. Abbott Labs may have a support program for Meridia similar to Xenicare's. But it, too, has struggled with prescription renewals.

Following are other appetite suppressants are available by prescription for diet and weight loss.

Ganes Chemicals is the only U.S. manufacturer left that makes the raw material used to produce Phentermine. It takes several months to make this raw material. This fact has contributed to periodic shortages (and accompanying rapid price increases) of phentermine, most recently during 1999. Due to the 1999 shortage it was estimated that prices soared ten-fold.

Phentermine, half of the controversial weight-loss combination fen-phen, is back, but this time it’s being combined with popular antidepressants to help people lose weight.

Although the phentermine-antidepressant cocktail has produced anecdotal reports of massive weight loss, it has also raised concerns because there aren’t long-term studies on safety and effectiveness. In addition, the combinations aren’t approved by the Food and Drug Administration and are strongly discouraged by some antidepressant makers.

"The Future of the treatment of obesity is going to be the use of combinations of drugs," says Richard L. Atkinson, professor of medicine at the University of Wisconsin in Madison and president of the American Obesity Association.

Phentermine has been available as a prescription weight loss drug for more than 40 years. It became a household name in 1997 when doctors began widely prescribing it in combination with fenfluramine. But the fen-phen cocktail ultimately was linked to serious heart-value problems and the fenfluramine half, which was implicated as the troublemaker, was pulled from the market.

Phentermine continues to be used as an appetite suppressant. The drug accounts for about half of all weight-loss prescriptions, in part because it’s significantly cheaper than the other major FDA approved diet drugs, Meridia and Xenical. Insurance companies typically don’t cover diet drugs.

Now, a handful of doctors have begun combining phentermine with other drugs, notably popular antidepressants such as Prozac, Effexor, and Celexa. Side effects can include dry mouth, insomnia, headaches, and constipation. The drug combinations are considered an "off label" use and aren’t sanctioned by the FDA.

Meridia is taken once a day, and will cost about $80 per month. Most people are limited to one year with this diet drug.

Phentermine is taken once per day, with a typical cost of $30-40 per month. This diet drug, which has been used for decades, originally had a limitation of 12-20 weeks. However, today it is commonly used for much longer periods with no problem. Many bariatricians use it with their patients for as long as several years. Some states may have limits, however. Adipex may be slightly more costly than other brand names of Phentermine (Fastin, Ionamin, etc.).

The above prices are for "traditional" prescriptions obtained after an in-person visit with your physician. Internet pharmacies generally charge higher prices, since they are also selling the "convenience" of obtaining these drugs without a visit to your doctor. This is a practice that will be coming under greater scrutiny by Congress in the near future. It is a very dangerous practice and is not advocated by BestDietForMe.com/Marketdata analysts and many others. Many feel that it is simply not possible to adequately evaluate a person’s complete health status over the phone or by filling out a brief survey on the Internet, for the purpose of prescribing medications.