Results of CAMELLIA-TIMI 61 trial of Belviq showing weight loss and incidence of CV events was presented at ECS Congress and published in NEJM.- Eisai.

Eisai Co., Ltd. has announced that results from the Cardiovascular Outcomes Trial (CAMELLIA-TIMI 61) in patients treated with lorcaserin hydrochloride (generic name, product name in the U.S.: Belviq ) were highlighted in an oral presentation at the European Society of Cardiology (ESC) Congress 2018 held in Munich, Germany, and concurrently published in the New England Journal of Medicine. Belviq is the first ever weight loss medication approved for chronic weight management which has been proven to not increase the incidence of major cardiovascular (CV) events in a dedicated long-term cardiovascular outcome trial.

This study was conducted at over 400 sites in eight countries including the United States in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, and is the largest cardiovascular outcome trial conducted to date for a weight loss medication.

As the primary safety objective, the study assessed the incidence of major adverse cardiovascular events (MACE: defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in 12,000 overweight and obese adults with existing cardiovascular disease or type 2 diabetes mellitus (T2DM) with cardiovascular risk factors who were administered Belviq 10 mg twice-daily (median 3.3 years). Overall, the median age of patients in the study was 64 and the median body mass index (BMI) was 35kg/m2, with 57% of patients at baseline having T2DM, 90% with hypertension, 94% with hyperlipidemia and 20% with chronic kidney disease. Approximately 75% of patients had established atherosclerotic CV disease. At the time of study completion, MACE occurred in 364 of 6,000 patients in the Belviq arm (2.0%/year) and 369 of 6,000 patients in the placebo arm (2.1%/year; hazard ratio, 0.99; 95% confidence interval (CI), 0.85-1.14; non-inferiority margin, 1.4). This demonstrated that Belviq did not increase the incidence of MACE, and therefore the primary safety objective of statistical non-inferiority was met.

Since the primary safety objective was met, the primary efficacy outcome of incidence of CV death, myocardial infarction, stroke hospitalization for unstable angina, heart failure or any coronary revascularization (MACE+) was also assessed. From the results, MACE+ occurred in 707 of 6,000 patients (4.1%/year) in the Belviq arm and in 727 of 6,000 patients in the placebo arm (4.2%/year). Although statistical superiority was not observed (p=0.55), statistical non-inferiority was confirmed (hazard ratio, 0.97; 95% CI, 0.87-1.07; non-inferiority margin, 1.4). In exploratory assessments of the efficacy of Belviq, at one year, significantly more patients treated with Belviq versus placebo lost greater than or equal to five percent of body weight (39% vs. 17%; nominal p-value<0.001) or greater than or equal to ten percent of body weight (15% vs. 5%; nominal p-value><0.001). the average change in weight from baseline was -4.2 kg with belviq and -1.4 kg with placebo, translating to a 2.8 kg greater net weight loss with belviq (nominal p-value><0.001).>

Furthermore, treatment with Belviq (for a period of one year), on top of standard of care for the respective comorbid conditions in CAMELLIA-TIMI 61, was associated with statistically significant improvements in systolic blood pressure (placebo-subtracted difference -0.9 mm Hg), diastolic blood pressure (-0.8 mm Hg), heart rate (-1.0 beat per minute), low-density lipoprotein cholesterol (-1.2 mg/dL), triglycerides (-11.7 mg/dL) and non-high-density lipoprotein cholesterol (-2.6 mg/dL). Belviq also reduced hemoglobin A1C (HBA1c) in patients with T2DM at baseline (placebo-subtracted difference -0.3%) and reduced the rate of new onset diabetes in patients with pre-diabetes at baseline (3.1%/year with Belviq versus 3.8%/year with placebo).

No significant differences were seen in the overall incidence of serious adverse events between Belviq and placebo (31% vs. 32%), and the overall safety profile for Belviq in CAMELLIA-TIMI 61 was consistent with that of the approved label. Dizziness, fatigue, headache, nausea and diarrhea were the most commonly reported adverse events in CAMELLIA-TIMI 61. Adverse events possibly leading to study discontinuation were more frequent with Belviq versus placebo (7.2% vs. 3.7%), with the most commonly reported adverse events in this category for Belviq being dizziness, fatigue, headache, diarrhea and nausea. Further results of analyses of the study will be presented on October 4 at the European Association for Study of Diabetes (EASD) Annual Meeting held in Berlin, Germany.

See- "Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients"-Erin A. Bohula, M.D., D.Phil., Stephen D. Wiviott, M.D., Darren K. McGuire, M.D., M.H.Sc., et al., for the CAMELLIA�TIMI 61 Steering Committee and Investigators*-August 26, 2018 DOI: 10.1056/NEJMoa1808721.