FDA: Weight Control Drug Lorcaserin May Raise Cancer Risk

In continuation of my update on lorcaserin

The prescription weight control medicine lorcaserin (Belviq, Belviq XR) may increase the risk for cancer, according to the results of a clinical trial assessing the safety of the drug, the U.S. Food and Drug Administration says.

The agency said, "[W]e cannot conclude that lorcaserin contributes to the cancer risk" but "wanted to make the public aware of this potential risk. We are continuing to evaluate the clinical trial results and will communicate our final conclusions and recommendations when we have completed our review."

Health care providers should balance the benefits of taking lorcaserin against the potential risks when deciding whether to prescribe or continue patients on the medication, the FDA advised. It said that patients currently taking lorcaserin should talk to their health care professionals about the potential increased risk for cancer with use of the medication.

Lorcaserin is approved for use with a reduced-calorie diet and increased physical activity to help weight loss in adults who are obese or are overweight and have weight-related medical problems. Lorcaserin increases feelings of fullness so that people eat less. It is available as a tablet (Belviq) and an extended-release tablet (Belviq XR).

https://en.wikipedia.org/wiki/Lorcaserin

Study provides insight into how weight-loss drug acts in the brain

In continuation of  my update on lorcaserin

A weight-loss drug dampened the response to food cues in regions of the brain associated with attention and emotion, leading to decreases in caloric intake, weight and body mass index (BMI), a team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) reported. In the first study of the drug lorcaserin in the human brain, the research revealed the mechanism underlying the drug's efficacy and provides insight into which individuals may benefit most from the medication. The paper was published today in the journal Diabetes, the journal of the American Diabetes Association.

"Human feeding behaviors involve areas of the brain responsible for cognitive control and decision-making," said Christos S. Mantzoros, MD, Director of the Human Nutrition Unit in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Professor of Medicine at Harvard Medical School. "We wanted to find out if lorcaserin was acting on these brain regions and, if so, where and how. One-third of the U.S. population is obese, and another one-third is overweight. This is a huge burden on individuals and the health care system. In addition, it increases the risk of diabetes, cardiovascular disease and many types of cancer. We need to continue to develop safe and effective therapies to combat this epidemic."

Approved by the FDA in 2012, the generic drug lorcaserin is a medication prescribed for obese or overweight adults who also have weight-related health complications such as diabetes. Several studies have shown the drug helps about half of the people who take it lose more than 5 percent of their body mass within a year, but there's a great deal of variability in individual results, and the mechanism underlying its effect was previously unknown.

To determine how the drug works in the human brain, Mantzoros and colleagues observed 48 obese men and women - half taking the drug, half taking a placebo - over the course of a four-week experiment. Participants came into the clinic on four occasions for blood work, physical exams, measurements and weight-loss counseling with a registered dietician. They were also expected to keep records of the food they ate during the study.

On three visits - before receiving any medication (Week 0), after a week of medication (Week 1), and after four weeks of medication (Week 4) - exams were followed by two brain scans: one after the patients had fasted for at least 12 hours, the other after they had eaten a meal. The scans were taken using functional magnetic resonance imaging (fMRI) to measure changes in blood flow in an active brain, which suggests which regions play a role during a given task. During each scan, participants were shown 150 images of foods generally considered highly desirable, such as cake and onion rings; foods generally considered less desirable like vegetables; and nonfood items like rocks and trees.

At Week 1, the fMRI scans in the fasting state revealed that people taking the drug showed decreased brain activity in response to images of highly desirable foods in the attention-related parietal and visual cortices. At Week 4, the lorcaserin group in the fed state showed less activity in the parietal cortex - which is responsible for integrating sensory information - when looking at any of the food images.

The data also revealed that subjects who had the strongest brain responses to food prior to taking lorcaserin saw the most success with the weight-loss medication.

"Decreases in caloric intake, weight, and BMI were linked to strong responses to food cues in the areas of the brain related to emotion, pleasure and attention prior to taking the weight-loss drug, which suggests that lorcaserin could prove to be of particular benefit to 'emotional eaters,' " Mantzoros said.Lorcaserin targets only a very specific serotonin receptor (known as 5-HT2c), shown in animal studies to play a role in abnormal food consumption. A previous generation of weight loss drugs was linked to this receptor, but because their scope was broader, those products also had dire cardiac side effects including pulmonary hypertension and valve problems. Lorcaserin could produce weight loss without these cardiac risks, the authors noted.

"In addition, the different mechanism of action in comparison to other drugs for obesity creates an opportunity for combination drugs for the treatment of obesity," Mantzoros said. "This might create more powerful solutions and is something that remains to be explored."

Lorcaserin Receives Positive Vote From FDA Advisory Committee

In continuation of my update on Lorcaserin

Lorcaserin Receives Positive Vote From FDA Advisory Committee:  

(FDA) Endocrinologic and Metabolic Drugs Advisory Committee voted 18 to 4, with one abstention, that the available data demonstrate that the potential benefits of lorcaserin outweigh the potential risks when used long-term in a population of overweight and obese individuals. Lorcaserin is an investigational drug candidate intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese (BMI greater than or equal to 30) or patients who are overweight (BMI greater than or equal to 27) and have at least one weight-related co-morbid condition.

"The advisory committee's positive vote supports our belief in lorcaserin as a potential new treatment option for the medical management of overweight and obesity," said Jack Lief, Arena's President and Chief Executive Officer. "We will continue to work with the FDA as the agency completes its review of the lorcaserin new drug application."

Eisai Inc. and Arena Pharmaceuticals Announce FDA Approval of Belviq XR (lorcaserin HCl) Extended-Release Tablets

In continuation of my update on Lorcaserin

Eisai Inc. and Arena Pharmaceuticals, Inc.   announced   the approval by  U.S. Food and Drug Administration (FDA)  the New Drug Application (NDA) for Belviq XR (lorcaserin HCl) CIV extended-release 20 mg tablets. The new formulation of lorcaserin will offer patients a once-a-day dosing option that may help them achieve and maintain weight loss. Belviq XR is expected to be available in the fall of 2016. In connection with the approval, Arena will receive a $10 million milestone payment.

Belviq XR is proven to be slowly absorbed in the body and lasts throughout the day. Both the original 10 mg twice-daily formulation of Belviq and newly-approved 20 mg once-daily extended release formulation are approved for use with a reduced-calorie diet and increased physical activity for chronic weight management in adults who have a body mass index (BMI) of 30 kg/m2 or greater (obese), or BMI of 27 kg/m2 or greater (overweight) with at least one weight-related medical condition, such as high blood pressure, high cholesterol, or type 2 diabetes. It is not known if Belviq or Belviq XR, when taken with other prescription, over-the-counter, or herbal weight-loss products, is safe and effective. It is not known if Belviq or Belviq XR changes your risk of heart problems, stroke, or death due to heart problems or stroke.

"With approximately two-thirds of the U.S. population living with extra weight or obesity, there is a significant and growing need to address chronic weight management," said Louis J. Aronne, M.D., Director of the Comprehensive Weight Control Center at Weill Cornell Medicine, physician at NewYork-Presbyterian/Weill Cornell Medical Center and Principal Investigator of the BELVIQ clinical trials. "Having a once-daily treatment may offer an option for patients to stay on track to meet their weight loss goals."

The bioequivalence and bioavailability of once-daily Belviq XR 20 mg compared with twice-daily Belviq 10 mg was based on two Phase 1 registrational clinical trials among healthy adult subjects. The most common treatment-emergent adverse events were similar to those seen in the Phase 3 clinical trials of Belviq 10 mg twice-daily.

"We're excited to offer this once-a-day option of lorcaserin," said Andrew Satlin, M.D., Executive Vice President, Neurology Business Group, Eisai Inc. "This option may provide another choice for patients who are overweight or obese and find it difficult to lose weight through diet and exercise alone. The development of this new formulation further underscores Eisai's ongoing commitment to help address the health care needs of this underserved population."

"We are pleased that once-daily Belviq XR has been approved by the FDA and will provide patients another option for weight loss," said Amit D. Munshi, Arena's President and Chief Executive Officer. "The approval of this new formulation is another example of Arena's success in supporting our collaborators."

What are Belviq and Belviq XR?

Belviq and Belviq XR are FDA-approved prescription weight-loss medications that, when used with diet and exercise, can help some overweight (Body Mass Index [BMI] ≥27 kg/m2) adults with a weight-related medical problem, or obese (BMI ≥30 kg/m²) adults, lose weight and keep it off.

It is not known if Belviq or Belviq XR when taken with other prescription, over-the-counter, or herbal weight-loss products is safe and effective. It is not known if Belviq or Belviq XR changes your risk of heart problems, stroke, or death due to heart problems or stroke.

Positive results from Phase 3 trial of wieght reducing drug Lorcaserin...

We knew that Lorcaserin, is a serotonergic weight-loss drug developed by Arena Pharmaceuticals. It is currently undergoing the final phase of clinical trials in preparation for submission for FDA approval.

Lorcaserin is a selective 5-HT2C receptor agonist and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus.

Mode of action : Arena believes that the activation of 5-HT2C receptors in the hypothalamus promotes weight loss through appetite suppression, and this is supported by animal studies, but it is unclear whether the dose range used in human trials will be sufficient to demonstrate the same level of weight loss. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, motor behavior, and endocrine secretion, the exact mechanism of appetite regulation is not yet known.

Arena reported positive, highly significant top-line results in September 2009. Arena will also present new data analyses from lorcaserin's successful Phase 3 pivotal program in oral and poster sessions. In an independent clinical symposium, expert academic scientists and physicians will spotlight the 5HT-2C mechanism for weight management. As per the claim by the company, the positive results from the Phase 3 pivotal program highlight lorcaserin's potential to provide physicians with a treatment option that combines three important attributes - efficacy, safety and tolerability. Hope in the days to come will have a drug to treat obesity too...

Ref : http://invest.arenapharm.com/releasedetail.cfm?ReleaseID=417902

Arena Pharmaceuticals and Eisai Announce FDA Approval of BELVIQ® (lorcaserin HCl) for Chronic Weight Management in Adults who are Overweight with a Comorbidity or Obese (NASDAQ:ARNA)

In continuation of my update on lorcaserin

Arena Pharmaceuticals and Eisai Announce FDA Approval of BELVIQ® (lorcaserin HCl) for Chronic Weight Management in Adults who are Overweight with a Comorbidity or Obese (NASDAQ:ARNA)

Diet Drugs: Which Ones Work?

Any of the prescription weight-loss drugs on the market can help obese people shed pounds, although some seem more effective than others, a new study finds.

Currently, five drugs are approved in the United States for managing obesity. But little has been known about how they stack up against one another, said Dr. Siddharth Singh, the lead researcher on the new study.

The findings  based on more than 29,000 people in total show all five drugs can work. But people on certain drugs tended to be more successful, at least over one year.

Specifically, people using Qsymia (phentermine-topiramate) or Victoza (liraglutide) had the highest odds of shedding at least 5 percent of their initial weight. Those taking Xenical (orlistat) had the lowest odds.

phentermine liraglutide

 orlistat  lorcaserin

 Bupropion/naltrexone 

However, there is no single drug that's "best" for everyone, stressed Singh, an assistant clinical professor at the University of California, San Diego.

He cautioned that his team's numbers are just averages across study groups. Plus, he said, the side effects of each medication vary, and that is an important factor in treatment decisions.

"Obesity treatment always needs to be personalized," Singh said.

Nikhil Dhurandhar, a spokesman for the Obesity Society, agreed that people respond differently to any given weight-loss drug.

"In general, if you give drug 'X,' there will be a wide variation in patients' responses," said Dhurandhar, who is also a professor of nutritional sciences at Texas Tech University in Lubbock. He wasn't involved in the study.

Some people will have "zero" weight loss   or even gain weight -- while others will see the pounds drop off, Dhurandhar said.

He also stressed that there is no such thing as a magic weight-loss pill.

"These drugs can help you eat less through effects on appetite," Dhurandhar explained. "But you have to change your diet and get regular exercise."

"Medications are supplements, not substitutes, to your efforts," he said.

For the study, Singh's team analyzed findings from 28 clinical trials testing the five approved drugs for obesity: Qsymia, Victoza and Xenical, along with Belviq (lorcaserin) and Contrave (naltrexone-bupropion).

On average, the researchers found, each drug worked better than a placebo in helping obese adults lose weight over a year. But certain medications seemed more effective than others.

People on Qsymia typically lost the most weight -- almost 20 pounds more, versus study patients given placebo pills. They were also nine times more likely to drop at least 5 percent of their initial weight, the researchers found.

People taking Xenical or Belviq tended to shed the fewest pounds -- 6 to 7 pounds more than placebo users. Contrave and Victoza patients typically lost 11 to 12 pounds more, compared with placebo.

But not everyone benefited. In studies of all of the drugs, Singh noted, a significant number of people dropped out because of side effects.

And those dropouts were more common with certain medications, the study found. People taking Contrave or Victoza were almost three times more likely to quit a trial over side effects, compared with placebo users. According to Victoza's maker, the drug can cause inflammation of the pancreas or kidney problems.

Just as people vary in their weight-loss success with any given drug, their risks of side effects will differ, too, Singh said.

He pointed to Contrave as an example. Because it contains the antidepressant bupropion, it carries a boxed warning about the potential risk of suicidal thoughts. So it might not be the best choice for someone with psychiatric conditions that could make them more vulnerable, Singh said.

Victoza, meanwhile, is an injection drug prescribed for controlling high blood sugar in people with type 2 diabetes. So if a patient needs medication for diabetes as well as weight loss, Victoza might be a good option, Singh said.

Most of the medications have been approved only in the past few years, so one question is whether they maintain their effects over the long run, Singh said.

"We do need more long-term data," Dhurandhar agreed.

Still, he said, medications are an important option for managing obesity. And if one does not work, Dhurandhar added, he'd recommend trying another.