Arena Pharmaceuticals, Inc. presented meta-analyses of the three trials in the lorcaserin phase III clinical trial programme at ECO 2011, the 18th European Congress on Obesity. The analyses show that lorcaserin caused statistically significant weight loss compared to placebo at one year among 7,500 obese and overweight, diabetic and non-diabetic adults. The lorcaserin-mediated weight loss was associated with favourable changes in biomarkers that may be predictive of cardiovascular and metabolic risk and in quality of life.
Christen M Anderson, MD, PhD, vice president, Arena Lorcaserin Development, stated, “We are pleased to have the opportunity to share and discuss the results from the lorcaserin phase III programme with the European medical community at ECO, and we look forward to submitting a Marketing Authorization Application for regulatory approval of lorcaserin in Europe next year.”
At one year, using Modified Intent-to-Treat with Last Observation Carried Forward analysis (MITT-LOCF) of the integrated results, 46.3% of lorcaserin 10 mg twice daily (BID) patients and 40.6% of lorcaserin 10 mg once daily (QD) patients achieved at least 5% weight loss, compared to 22.1% of patients on placebo, and 22.0% of lorcaserin 10 mg BID patients and 17.3% of lorcaserin 10 mg QD patients achieved at least 10% weight loss, compared to 8.3% of patients on placebo. Of the patients completing year one of the trials, 62.3% of lorcaserin 10 mg BID patients and 52.8% of lorcaserin 10 mg QD patients achieved at least 5% weight loss, compared to 32.0% of patients on placebo, and 33.5% of lorcaserin 10 mg BID patients and 25.5% of lorcaserin 10 mg QD patients achieved at least 10% weight loss, compared to 13.8% of patients on placebo. Notably, this meta-analysis included approximately 600 patients enrolled with type 2 diabetes, a disease that typically makes weight loss more difficult to achieve.
Changes in secondary endpoints of cardiovascular and metabolic risk were assessed in the phase III programme. Body Mass Index (BMI), waist circumference, triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, heart rate and quality of life were measured in all three trials in the phase III programme, and the integrated Year 1 results showed favorable statistically significant effects with lorcaserin 10 mg BID treatment compared to placebo. Lorcaserin did not increase heart rate or blood pressure; changes from baseline for patients who took lorcaserin 10 mg BID, lorcaserin 10 mg QD or placebo, respectively, were as follows: systolic blood pressure (mmHg), (-0.9, -0.2, -0.2); diastolic blood pressure (mmHg), (-1.4, -0.5, -0.8); and heart rate (bpm), (-1.0, -0.5, -0.2).
The most frequent lorcaserin-associated adverse events included headache, nausea, dizziness, fatigue and dry mouth. Headache was the only adverse event with an incidence that exceeded the placebo group by greater than 5%. In each trial, echocardiograms were performed at baseline and every six months to measure heart valve regurgitation. In the meta-analysis of the three trials, the proportion of patients who developed FDA-defined valvulopathy (moderate or greater mitral insufficiency and/or mild or greater aortic insufficiency) at Week 52 were as follows: lorcaserin 10 mg BID (2.37%), lorcaserin 10 mg QD (1.57%) and placebo (2.04%).
“There is a significant unmet need for effective treatment options that can help patients reduce their weight and improve their health in a well-tolerated manner,” said William R Shanahan, MD, senior vice president and chief medical officer, Arena. “A diverse group of patients received lorcaserin in our phase III programme and achieved clinically meaningful weight loss and improvements in important cardiovascular and metabolic parameters.”
The three lorcaserin phase III trials randomized a total of 7,794 patients, and 7,500 patients were included in the primary efficacy analyses (MITT-LOCF), which required a patient to have taken at least one dose of study medication and have had at least one weight measurement subsequent to baseline. The MITT-LOCF analyses included 3,349 lorcaserin 10 mg BID patients, 865 lorcaserin 10 mg QD patients and 3,286 placebo patients. Patients had an average BMI, baseline weight and age of approximately 36 kg/m2, 100 kg and 45 years, respectively; approximately 80% of patients were female.
Lorcaserin is an investigational drug candidate intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese (BMI >30) or patients who are overweight (BMI >27) and have at least one weight-related co-morbid condition. Lorcaserin is a new chemical entity that is believed to act as a selective serotonin 2C receptor agonist. The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area believed to be involved in the control of appetite and metabolism. Arena has patents that cover lorcaserin in the United States and other jurisdictions that in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity Arena might obtain.
Arena submitted a New Drug Application (NDA) for lorcaserin to the US Food and Drug Administration (FDA) in December 2009, and the FDA issued a Complete Response Letter (CRL) in October 2010. Arena is engaged in activities to address the issues raised by the FDA as part of its plan to submit a response to the CRL.
The lorcaserin phase III clinical trial programme consists of three double-blind, randomized, placebo-controlled trials, BLOOM (Behavioural modification and Lorcaserin for Overweight and Obesity Management), BLOSSOM (Behavioural modification and LOrcaserin Second Study for Obesity Management) and BLOOM-DM (Behavioural modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus), and enrolled approximately 7,800 patients. BLOOM and BLOSSOM evaluated lorcaserin versus placebo in patients who are obese or patients who are overweight and have at least one weight-related co-morbid condition. BLOOM evaluated 3,182 patients over a two-year treatment period, and BLOSSOM evaluated 4,008 patients over a one-year treatment period. BLOOM-DM evaluated 604 obese and overweight patients with type 2 diabetes over a one-year treatment period. The trials included a standardized programme of moderate diet and exercise guidance.
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.