Obesity, a public health epidemic is growing at an alarming rate not only in developed countries but in developing nations as well. Given the growing unmet demand and patients clamoring for a quick remedy, a weight-loss drug with a high benefit to risk ratio can be expected to achieve a blockbuster status. However, a really effective and safe weight-loss therapy is long overdue.
According to the National Center for Health Statistics, 34% of American adults are obese and 32.7% are overweight. A person with a body mass index, or *BMI, of 25-29.9 is said to be overweight, while an obese person will have a BMI of 30 or more. (*BMI is a measure of body fat based on height and weight).
Obese people are often at risk for type II diabetes, cardiac disorder, and hypertension. A study conducted by researchers at the German Institute of Human Nutrition, the results of which were published in November 13, 2008 issue of the New England Journal of Medicine reveals that "for every 5-centimeter increase in waist circumference, the chances of death rose 17% for men and 13% for women."
It is claimed that obesity is responsible for over 300,000 deaths a year in the U.S. With obesity set to remain a leading health problem for years to come, the anti-obesity drug treatment market can be expected to offer immense opportunities for drug companies involved in developing weight-loss drugs, provided the drug is safe and really effective.
Arena Pharmaceuticals Inc. (ARNA), Orexigen Therapeutics Inc. (OREX) and Vivus Inc. (VVUS), which are racing to find a prescription diet drug, presented positive study results of their investigational drugs at the American Diabetes Association's, or ADA's, 69th Scientific Sessions in New Orleans, Louisiana on Saturday.
Arena Pharma reported additional data from its late-stage trial dubbed BLOOM, which showed that its experimental drug Lorcaserin helped patients achieve highly significant categorical and absolute weight loss in the first year, and continued treatment with Lorcaserin in the second year helped significantly more patients maintain their weight loss as compared to those on placebo.
According to Arena, treatment with Lorcaserin also resulted in highly significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk. Lorcaserin did not result in increased risk of depression and was not associated with the development of cardiac valvular insufficiency.
In March, Arena stock got battered despite the company reporting positive top-line results from the BLOOM study. The trial results reported in March revealed that 47.5% of patients treated with Lorcaserin lost greater than or equal to 5% of their body weight from baseline compared to 20.3% in the placebo group.
Average weight loss in the Lorcaserin group was 5.8% of body weight, or 12.7 pounds, compared to 2.2% of body weight, or 4.7 pounds. Thus, the placebo-adjusted weight loss works out to 3.6%.
According to the FDA approval standards for diet drugs, the difference in average weight loss between the investigational drug and placebo-treated groups should be at least 5% or the proportion of patients who lose greater than or equal to 5% of baseline body weight in the treatment group should be at least 35%. Though it is not necessary that a drug should satisfy both the benchmarks, investors were disappointed with the inferior placebo-adjusted weight loss percentage and drove the company's stock price down by 28% to $3.23 on March 30.
Arena Pharma is on track to announce the results of its second late-stage trial BLOSSOM in September and file its New Drug Application for Lorcaserin by the end of the year.
ARNA, which has been trading in the range of $2.26 - $7.42 over the past twelve months, closed Monday's trade at $4.94.
Orexigen Therapeutics Inc. (OREX) announced additional positive findings from NB-302, the first of four phase III trials of its investigational weight-loss drug Contrave on Saturday.
The NB-302 results show that Contrave initiates and sustains weight loss and can improve predictive markers for heart disease such as waist circumference, triglycerides, HDL-cholesterol and hsCRP.
Orexigen also revealed that Contrave was not associated with suicidality or worsening of mood or depressive symptoms, and in fact was associated with a decreased incidence of treatment-emergent depression compared to placebo. In addition, patients treated with Contrave achieved significant improvements in overall quality of life and benefits, such as improved physical function and self-esteem, occurred early in treatment and were maintained over one year.
Early this year, Orexigen reported that in the NB-302 trial, obese patients treated with Contrave lost an average of 20.3 pounds to 25.0 pounds, or 9.3% to 11.5% of their baseline body weight, compared to 11.0 pounds to 16.0 pounds, or 5.1% to 7.3% of baseline body weight, for patients treated with placebo. The placebo-adjusted weight loss works out to 4.2%. In addition, in the categorical weight reduction analysis, the percentage of patients who lost greater than or equal to 10% of their body weight was 41.5% in the Contrave group, compared to 20.2% in the placebo group. As in the case of Arena, since the placebo-adjusted weight loss percentage was less than the FDA benchmark of 5%, investors were disappointed and the stock lost nearly 16% and fell to $5.10, following the release of the trial results on January 9.
Orexigen expects to report results from the three other phase III trials (NB-301, NB-303, NB-304) in the third quarter of 2009. Pending positive results, the company is on track to submit a New Drug Application for Contrave with the FDA in the first half of 2010.
Thus far, OREX has hit a 52-week low of $1.55 and 52-week high of $12.28. The stock closed Monday's trade at $3.88.
At the ADA Annual Meeting, Vivus Inc. (VVUS), yet another company, which is developing a prescription diet drug, revealed the glycemic findings from EQUATE (OB-301), a phase III trial evaluating its investigational drug Qnexa in non-diabetic, obese patients.
According to the company, after 28 weeks of treatment, blood sugar levels, as measured by hemoglobin A1c (HbA1c), were lower in the patients treated with Qnexa, while the patients in the placebo group had a significant increase in their HbA1c levels.
Vivus also reported the results of a phase II trial dubbed DM-230 evaluating Qnexa in patients with type 2 diabetes. The clinical trial revealed that Qnexa, significantly reduced patients' hemoglobin A1c (HbA1c) -- a key indicator of blood sugar control -- and helped patients achieve and maintain significant weight loss. The study also showed that Qnexa had a positive impact on other risk factors associated with diseases prevalent in people living with diabetes.
In the phase II trial, patients treated with Qnexa lost 9.4% of their baseline body weight, or 20.5 pounds, compared to 2.7%, or 6.1 pounds, for the placebo group. About 65% of the patients treated with Qnexa lost at least 5% of their body weight compared to 24% in the placebo group.
Last December, Vivus reported that the EQUATE study met the primary endpoint by demonstrating superior weight loss with Qnexa. Subjects treated with full-dose and mid-dose Qnexa had an average weight loss of 9.2% and 8.5% respectively, compared to weight loss of 1.7% reported in the placebo group. The differences between the treatment groups and placebo were 7.5% and 6.8%, respectively, which were well above the FDA's benchmark of 5% difference.
The average weight loss in the EQUATE study was 19.8 pounds and 18.2 pounds in the treatment arms as compared to 3.3 pounds in the placebo group. Qnexa was well-tolerated, with no drug-related serious adverse events in the study.
In addition to the EQUATE study, the phase III Qnexa program also includes trials -- CONQUER (OB-303) and EQUIP (OB-302), which are currently underway. Vivus expects to report the results of these trials in the third-quarter of this year.
VVUS, which has been trading in the range of $2.72 - $9.27 for the past twelve months, closed Monday's trade at $5.49.
Market Opportunities
The market for anti-obesity drugs is virtually untapped and continues to hold a glittering allure. Till date there has been no 'silver bullet' remedy for obesity. Analysts estimate that the potential market for obesity drug ranges from $5 billion to $10 billion per year.
A couple of approved diet drugs have been recalled, following reports of adverse side reactions like heart damage and some of the investigational obesity drugs have gone belly-up. Abbott Laboratories' (ABT) Meridia and Roche's Xenical are the only two FDA-approved prescription anti-obesity drugs currently on the market. GlaxoSmithKline plc's (GSK) Alli is the only FDA-approved, over-the-counter weight-loss product.
Meridia, which was approved by the FDA in 1997, works by acting on certain brain chemicals that regulate appetite and reduce food intake by increasing a feeling of fullness.
Xenical does not interfere with the appetite but reduces the absorption of dietary fat into the bloodstream. The drug was approved by the FDA in 1999.
The safety and efficacy of Meridia have been questioned by its opponents ever since reports of adverse reactions to the diet drug surfaced in 2002. That year, the consumer-protection group Pubic Citizens petitioned to the FDA to recall Meridia saying that the risk of use outweighed the benefit, and described the drug as "unacceptably dangerous."
However, in 2005, the regulatory agency refused to ban Meridia saying "overall risk-benefit profile supports it remaining available as a prescription drug for the treatment of appropriately selected obese patients."
The FDA has strengthened the warnings in Meridia's labeling. Early this year, the FDA expanded its nationwide alert to consumers about tainted weight loss pills that contain undeclared, active pharmaceutical ingredients. As of date, the list of tainted weight-loss drugs number about 70 and some of these drugs have been found to contain undeclared active pharmaceutical ingredients like sibutramine and rimonabant. Sibutramine is the active ingredient in Meridia and Rimonabant was the active ingredient in the recalled Acomplia.
The UN's World Health Organisation, or WHO, estimates that in 2015, the number of obese people around the world will surge to more than 700 million, up from 400 million adults who were obese in 2005.
Headstones In Graveyard Of Obesity Drugs
The drug therapy for treatment of obesity has a checkered past. There have been a recall of obesity drugs and some of the drugmakers have abandoned potential obesity drugs - some of which were under late-stage development.
Fen-phen, a combination drug of Phentermine and Fenfluramine, and a related drug Redux marketed by Wyeth were withdrawn from the U.S. market in September 1997 after the drugs were found to be associated with a serious heart condition known as valvular regurgitation, or leaky heart valves.
In November 2008, Solvay Pharmaceuticals pulled the plug on its obesity compound SLV319, which was under phase II development, citing the current stringent regulatory environment. According to the company, the discontinuation was not related to any adverse events or the efficacy of the compound.
Considering the changing regulatory perspectives on the risk/benefit profile of the cannabinoid type 1 class of drugs, Pfizer Inc. (PFE) abandoned the development of CP-945598 (Otenabant) for weight management in early November last year. CP-945598, a selective antagonist of the cannabinoid type 1 receptor was in late-stage development when the company pulled the plug on the trial.
Yet another investigational obesity drug, which was under phase III development, to bite the dust last year was Merck's Taranabant. Merck halted development of the drug in early October as it had too many side effects. Though Taranabant was considered a potential blockbuster, some analysts were wary of the drug's approval as it belonged to the same class as Sanofi-Aventis' (SNY) weight-loss drug Acomplia. In June 2007, the FDA rejected Acomplia saying that the drug's benefits did not outweigh its risks.
The much-touted Acomplia, which was approved in the EU (European Union) in 2006, also had an abrupt end last year. With new data from post-marketing trials linking the drug to serious psychiatric disorders, Sanofi-Aventis on the recommendation of the EMEA, withdrew Acomplia from the European markets in late October last year. The drug had been on sale in the EU for over two-and-a half years.
Closing Thoughts
Even the deep-pocketed pharma giants have failed in their quest to strike gold with obesity drugs. But that has not deterred fledgling biotechs from joining in the race to create the magic pill. The market for anti-obesity drugs has a huge untapped potential and there is enough room for all the players. But the first company to hit the market with a safe and effective weight-loss drug could reap huge profits.
...So who will win the race to find a "cure" for obesity? Stay tuned.
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June 05, 2026 16:18 ET A busy week for economic news flow saw a slew of reports being released that reflected the trends in the U.S. labor market. In Europe, economic growth and inflation data gained attention as the European Central Bank and Bank of England head for policy session later in the month. In Asia, the monetary policy session of the Indian central bank was in focus as the country, a major oil importer, reels under the pressures of a weaker rupee and rising inflation.