Eisai Inc. and Arena Pharmaceuticals, Inc. announced top-line results from the phase 2 trial investigating lorcaserin HCl, a serotonin 2C receptor agonist, for smoking cessation. The trial demonstrated statistically significant improvement over placebo in reducing the number of patients who smoke after 12 weeks of treatment. The detailed results of the trial are expected to be presented at a future scientific meeting.
Lorcaserin is an investigational product for smoking cessation. The efficacy and safety of lorcaserin for smoking cessation have not been established.
"We are pleased that this proof-of-concept trial provides what we believe is the first clinical evidence that a selective serotonin 2C agonist may have a treatment effect for smoking cessation," said Jack Lief, Arena's president and chief executive officer. "We will evaluate the full data set to determine next steps regarding further development of lorcaserin for this potential indication."
The 12-week, randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of lorcaserin as a potential aid to smoking cessation. In the trial, 603 active smokers were randomized to receive lorcaserin 10 mg once daily (QD), 10 mg twice daily (BID) or placebo in a 1:1:1 ratio. Patients at baseline were dependent on nicotine and averaged 18 cigarettes per day. Patients were dosed for two weeks before attempting to quit around Day 15 of the trial and received smoking cessation counseling during the trial.
"Smoking is recognized as one of the greatest global public health challenges, but unfortunately millions of people around the world continue to smoke and find it hard to quit," said Gary Palmer, MD, Eisai's chief medical officer. "These data advance our knowledge about lorcaserin and its potential development as an aid to smoking cessation."
The primary objective of the trial was assessment of smoking cessation efficacy. The carbon monoxide confirmed continuous abstinence rate (CAR), defined as no reported smoking or other nicotine use and an end-expiratory exhaled carbon monoxide measurement of less than or equal to ten parts per million, measured during the last four weeks of the trial (Weeks 9-12), was the basis for determining efficacy. The primary endpoint was achieved by 5.6%, 8.7%, and 15.3% of patients in the placebo, QD and BID groups, respectively (p-value = 0.003 and odds ratio = 3.02 for BID vs. placebo; the result for QD vs. placebo was not statistically significant).
Secondary objectives for the trial included assessment of body weight change and of safety and tolerability. At Week 12 in the MITT population, there was a statistically significant difference in weight between lorcaserin BID and placebo (-0.98 kg and -0.01 kg, respectively, p-value = 0.0004).
The overall adverse event profile appears similar to the profile in previous trials of lorcaserin, with the most common adverse events being headache, nausea, constipation, dizziness and dry mouth.
Arena and Eisai share the development costs of the smoking cessation development programme.
Internally discovered at Arena, lorcaserin is believed to selectively activate serotonin 2C receptors in the brain. Preclinical data suggest that serotonin 2C receptors may modulate the mesolimbic dopaminergic reward system. The exact mechanism of action of lorcaserin is not known.
Lorcaserin is marketed in the United States under the brand name Belviq. Belviq is a serotonin 2C receptor agonist approved as an adjunct to 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 is safe and effective when taken with other prescription, over-the-counter, or herbal weight loss products, nor is it known if Belviq changes the risk of heart problems or stroke, or death due to heart problems or stroke.
Belviq is believed to decrease food consumption and promote satiety by selectively activating serotonin 2C receptors in the brain. The exact mechanism of action of Belviq is not known.
Eisai is responsible for the marketing and distribution of Belviq in most territories worldwide under its agreement with Arena. Belviq is a registered trademark of Arena Pharmaceuticals GmbH.
Arena is embracing the challenge of improving health by seeking to bring innovative medicines targeting G protein-coupled receptors to patients. Arena's internally discovered drug, Belviq (lorcaserin HCl), is approved in the United States, and Arena is focused on discovering, developing and commercializing additional drugs to address unmet medical needs.