WOODCLIFF LAKE, N.J., Oct. 4, 2018 /PRNewswire/ -- Eisai Inc. announced today new data on prevention and remission of diabetes from the CAMELLIA-TIMI 61 cardiovascular (CV) outcomes trial in patients treated with anti-obesity agent BELVIQ^® (lorcaserin HCl) CIV 10 mg twice-daily that were presented at the 54^th Annual meeting of the European Association for the Study of Diabetes (EASD) and concurrently published in The Lancet. This new analysis assessed metabolic effects on enrolled patients with type 2 diabetes mellitus (T2DM), pre-diabetes, and normoglycemia at baseline.

In the pre-specified secondary efficacy analysis in patients with pre-diabetes, treatment with BELVIQ compared to placebo reduced the risk of incident diabetes by 19% (8.5% vs. 10.3%; HR 0.81; 95% CI: 0.66-0.99; nominal p-value=0.038). Furthermore, lorcaserin tended to increase the rate of achievement of normoglycemia in patients with pre-diabetes (9.2% vs. 7.6%; HR 1.20, 0.97-1.49; nominal p-value=0.093) and increased the rate of remission of hyperglycemia in patients with diabetes (7.1% vs. 6.0%; HR 1.21, 1.00-1.45; nominal p-value=0.049). Additionally, in exploratory analyses, at 1 year, lorcarserin compared to placebo reduced HbA1c in patients with T2DM by 0.33% (95% CI: −0.38 to −0.29; nominal p-value<0.0001) from a mean baseline of 7.0%. In the 1,100 patients with T2DM with a baseline HbA1c greater than 8.0%, the mean reduction in HbA1c at 1 year was 0.87% (95% CI: 0.76−0.97) with lorcaserin compared with 0.35% (0.23−0.46) for placebo, translating into a net reduction of 0.52% (0.37−0.68; nominal p-value<0.0001). Treatment with BELVIQ also reduced the risk of a composite of microvascular events of incident microalbuminuria, diabetic retinopathy or neuropathy by 21% in patients with diabetes (10.1% vs. 12.4%; HR 0.79; 95% CI: 0.69-0.92; nominal p-value=0.001).

Additionally, in patients with diabetes at baseline hypoglycemia occurred in 6.6% of patients treated with BELVIQ versus 5.8% in those treated with placebo, with most (>85% of events) occurring in patients on either insulin or a sulfonylurea at baseline (196 vs. 171 events of hypoglycemia; nominal p-value=0.18). Severe hypoglycemia with serious complications was rare, but more common with BELVIQ versus placebo (0.4% vs. 0.1%), respectively.

In exploratory analyses after 1 year, net weight loss was greater with BELVIQ compared with placebo for patients with T2DM (least-squares mean treatment difference at 1 year (-2.6 kg [95% CI: -2.9, -2.3], nominal p-value<0.0001), pre-diabetes (-2.8 kg [-3.2, -2.5], nominal p-value<0.0001) and normoglycemia (-3.3 kg [-4.0, -2.6], nominal p-value<0.0001). At 1 year, more patients randomized to BELVIQ versus placebo lost ≥5% of body weight in each subgroup: T2DM (37% vs 17%, nominal p-value<0.0001), pre-diabetes (40% vs 18%, nominal p-value<0.0001) and normoglycemia (42% vs 17%, nominal p-value<0.0001). The between-treatment group weight loss remained significant within each glycemic subgroup over the duration of the trial.

"The prevalence of diabetes is growing, which is likely related in part to the increasing prevalence of obesity," said Erin Bohula, MD, DPHIL cardiologist and staff investigator, TIMI Study Group, Brigham and Women's Hospital. "These data provide valuable information to doctors treating patients that are overweight and obese with T2DM or who are at risk of developing T2DM."

The overall safety profile for BELVIQ in CAMELLIA-TIMI 61 was consistent with that of the approved label, with dizziness, fatigue, headache, nausea, and diarrhea being the most commonly reported adverse events observed in CAMELLIA-TIMI 61.

No significant differences were seen in the overall incidence of serious adverse events between BELVIQ and placebo (31% vs. 32%). Adverse events attributed to study drug and leading to drug discontinuation were more frequent with BELVIQ versus placebo (7.2% vs. 3.7%), respectively, with the most commonly reported adverse events in this category for BELVIQ being dizziness, fatigue, headache, diarrhea, and nausea.

"Adults with diabetes are two to four times more likely to die from heart disease compared to adults without diabetes," said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. "Eisai is committed to furthering the study of BEVLIQ and assessing its potential in addressing risk factors such as diabetes and heart disease in overweight and obese patients."

CAMELLIA-TIMI 61 was a randomized, double-blind, placebo-controlled, multinational clinical trial that investigated the long-term CV and metabolic safety and efficacy of BELVIQ in obese or overweight patients with or at high risk for diabetes and adverse CV events. The primary objectives of the study were previously reported and published in the New England Journal of Medicine on August 26^th.

The study was conducted in collaboration with the Thrombolysis in Myocardial Infarction (TIMI) Study Group of Brigham and Women's Hospital, was a 12,000 patient study of BELVIQ at over 400 sites in eight countries, including the United States, and is the largest CV outcomes trial to date for a weight loss medication. At baseline, the study enrolled 6,816 patients with T2DM (57%), 3,991 patients with pre-diabetes (33%), and 1,193 patients with normoglycemia (10%). Patients with T2DM were eligible for enrollment if they had a screening hemoglobin A1c of <10% and a stable clinical and treatment course of T2DM in the preceding three months with no hospitalizations for hypo- or hyperglycemia. In the absence of prevalent T2DM, pre-diabetes was defined as a hemoglobin ≥5.7%-<6.5% or a fasting plasma glucose of 100-125mg/dL.

This release discusses investigational uses for FDA-approved products. It is not intended to convey conclusions about efficacy and safety. There is no guarantee that any investigational uses of FDA-approved products will successfully complete clinical development or gain FDA approval.

About BELVIQ^®

BELVIQ^®/BELVIQ XR^® is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m² or greater (obese), or 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes).

Limitations of Use:

• The safety and efficacy of co-administration of BELVIQ/BELVIQ XR with other products intended for weight loss, including prescription drugs (e.g., phentermine), over-the-counter drugs, and herbal preparations, have not been established.
• The effect of BELVIQ/BELVIQ XR on cardiovascular morbidity and mortality has not been established.

About the Study

The CAMELLIA (Cardiovascular And Metabolic Effects of Lorcaserin In Overweight And Obese Patients) TIMI 61 study was the largest double-blind, placebo-controlled, parallel-group Phase IIIB/IV study among weight loss medications. The study consisted of over 12,000 overweight and obese patients with established CV disease or CV risk factors.

The study exclusively enrolled patients at high risk for a CV event.  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 type 2 diabetes mellitus (T2DM), 90% with hypertension, 94% with hyperlipidemia, 20% with chronic kidney disease and approximately 30% with obstructive sleep apnea. Approximately 75% of patients had established atherosclerotic CV disease. 

The primary safety objective was to evaluate that BELVIQ did not increase the incidence of major adverse cardiovascular events (MACE), defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. If the primary safety objective was met, the efficacy objective was to evaluate the impact of BELVIQ on reducing the incidence of MACE+, defined as MACE or hospitalization due to unstable angina or heart failure, or any coronary revascularization. Secondary objectives included evaluation to reduce incidence of conversion to T2DM in patients with pre-diabetes or no diabetes at baseline and improvement of glycemic control in patients with T2DM.

CAMELLIA-TIMI 61 met its primary safety objective, finding that long-term treatment with BELVIQ did not increase incidence of MACE, defined as cardiovascular death or non-fatal myocardial infarction or non-fatal stroke, in overweight and obese patients at high risk for CV events. With this result, BELVIQ is the first-ever weight loss medication approved for chronic weight management to achieve this objective in a dedicated long-term cardiovascular outcome trial.   

Since the study met the primary safety endpoint for MACE, the study also assessed for the primary efficacy endpoint of whether or not BELVIQ reduced the incidence of cardiovascular events compared to placebo for a broader composite endpoint, MACE+. Although superiority to placebo was not met, BELVIQ was non-inferior to placebo on the MACE+ composite, with similar event rates for BELVIQ and placebo.

Important Safety Information

Contraindication

• Pregnancy: BELVIQ/BELVIQ XR should not be taken during pregnancy or by women who are planning to become pregnant.
• Hypersensitivity: Patients with prior hypersensitivity reactions to lorcaserin or to any of the product components should not take BELVIQ/BELVIQ XR.

Warnings and Precautions

• Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions: BELVIQ/BELVIQ XR is serotonergic drugs. The development of potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported during use of serotonergic drugs, and dopamine antagonists, particularly when used in combination. Patients should be monitored for the emergence of serotonin syndrome symptoms or NMS-like reactions. Manage with immediate discontinuation of BELVIQ/BELVIQ XR and any concomitant serotonergic or antidopaminergic agents and initiate supportive symptomatic treatment.

• Valvular heart disease: Patients should not take BELVIQ/BELVIQ XR in combination with potent 5-HT2B receptor agonists that have been associated with regurgitant valvular heart disease. Use BELVIQ/BELVIQ XR with caution in patients with congestive heart failure (CHF). Evaluate patients who develop signs and symptoms of valvular heart disease and consider discontinuation of BELVIQ/BELVIQ XR.

• Cognitive impairment: Impairment in cognitive function has been reported in patients taking BELVIQ. Patients should use with caution when operating heavy machinery.

• Psychiatric disorders: The recommended daily dose should not be exceeded, as higher doses may cause psychiatric disorders. Discontinue BELVIQ/BELVIQ XR in patients who develop suicidal thoughts or behaviors.

• Hypoglycemia: Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus who are being treated with antidiabetic medications measure blood sugar levels before and during treatment with BELVIQ/BELVIQ XR and consider changes in medication regimen.

• Priapism: Men who experience priapism should immediately discontinue BELVIQ/BELVIQ XR and seek emergency medical attention. BELVIQ/BELVIQ XR should be used with caution with erectile dysfunction medications, in men who have conditions that might predispose them to priapism  or in men with anatomical deformation of the penis.

• Heart rate decreases: BELVIQ/BELVIQ XR may cause a slow heartbeat and should be used with caution in patients with a history of bradycardia or heart block greater than first degree.

• Additional Considerations: Consider monitoring for CBC changes, signs and symptoms of prolactin excess, and pulmonary hypertension.

Most Common Adverse Reactions:

• BELVIQ^® - in patients without diabetes: headache (17%), dizziness (9%), fatigue (7%), nausea (8%), dry mouth (5%), and constipation (6%); in patients with diabetes: hypoglycemia (29%), headache (15%), back pain (12%), cough (8%), and fatigue (7%).
• BELVIQ XR^® - common side effects in patients on BELVIQ XR were similar to those seen in patients on BELVIQ.

Nursing Mothers

• BELVIQ/BELVIQ XR should not be taken by women who are nursing.

BELVIQ^®/BELVIQ XR^® is a federally controlled substance (CIV) because they may be abused or lead to dependence.

For more information about BELVIQ/BELVIQ XR, see full Prescribing Information.

About Obesity

Obesity is a serious and growing public health issue. The prevalence of obesity in the U.S. has more than doubled among adults in the past 30 years. Approximately 69 percent of American adults over the age of 20 are affected by obesity and overweight. This dramatic rise in obesity has also had a major impact on other diseases. Indeed, obesity is an important risk factor for heart disease and stroke, directly or indirectly through intervening risk factors, such as hypertension, dyslipidemia, and diabetes.

About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal. We give our first thoughts to patients and their families, and helping to increase the benefits health care provides. As the U.S. pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a passionate commitment to patient care that is the driving force behind our efforts to discover and develop innovative therapies to help address unmet medical needs.

Eisai is a fully integrated pharmaceutical business that operates in two global business groups: oncology and neurology (dementia-related diseases and neurodegenerative diseases). Each group functions as an end-to-end global business with discovery, development, manufacturing and marketing capabilities. Our U.S. headquarters, commercial and clinical development organizations are located in New Jersey; our discovery labs are in Massachusetts and Pennsylvania; and our global demand chain organization resides in Maryland and North Carolina. To learn more about Eisai Inc., please visit us at www.eisai.com/US and follow us on Twitter and LinkedIn.

SOURCE Eisai Inc.