Eisai Announces Long-Term Cardiovascular Outcomes Data for Anti-Obesity Agent BELVIQ® Presented at the European Society of Cardiology and Published in the New England Journal of Medicine

WOODCLIFF LAKE, N.J., Aug. 27, 2018 /PRNewswire/ -- Eisai Inc. announced today that results from the CAMELLIA-TIMI 61 cardiovascular (CV) outcomes trial in patients treated with BELVIQ^® (lorcaserin HCl) CIV 10 mg twice-daily were presented at the European Society of Cardiology (ESC) Congress 2018 and concurrently published in the New England Journal of Medicine. As previously reported, the study met its primary safety objective and met the FDA-mandated criteria for cardiovascular safety, finding that long-term treatment with BELVIQ did not increase the incidence of major adverse cardiovascular events (MACE) in overweight and obese patients at high risk for a CV event. With this result, BELVIQ is the first-ever weight loss medication approved for chronic weight management to achieve this objective in a dedicated CV outcomes trial. In addition, exploratory assessments of the efficacy of BELVIQ on change in weight from baseline was improved over the duration of the study, out to more than three years. Improvements in the CV and metabolic profiles of patients treated with BELVIQ were also observed in exploratory endpoints.

CAMELLIA-TIMI 61, 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. The study was conducted as part of a post-marketing requirement by the U.S. Food and Drug Administration (FDA). The primary objective was evaluating long-term CV safety, by assessing the incidence of MACE in overweight and obese adults with existing CV disease or type 2 diabetes mellitus (T2DM) with 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.

In this large, dedicated CV outcomes trial of patients with high risk for a CV event, BELVIQ did not increase the incidence of MACE. At the time of study completion, MACE occurred in 364 patients in the BELVIQ arm (2.0%/year) and 369 patients in the placebo arm (2.1%/year; hazard ratio, 0.99; 95% confidence interval [CI], 0.85-1.14; p for noninferiority < 0.001).

Exploratory assessments of the efficacy of BELVIQ showed that BELVIQ more than tripled the odds of achieving at least 5% or 10% weight loss compared to placebo. At one year, more patients treated with BELVIQ versus placebo lost greater than or equal to five percent of body weight (39% vs. 17%; odds ratio [OR] 3.01; 95%CI 2.74-3.30; nominal p-value<0.001) or greater than or equal to 10 percent of body weight (15% vs. 5%; OR 3.40; CI: 2.92-3.95; 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). This difference remained significant through 40 months [-4.0kg (95%CI -4.3, -3.8) with BELVIQ vs. -2.1kg (95%CI, -2.3, -1.8) with placebo; treatment difference -1.9kg (95%CI -2.3, -1.6; nominal p-value<0.001)].

Furthermore, treatment with BELVIQ, on top of standard of care for the respective comorbid conditions in CAMELLIA-TIMI 61, was associated with improvements at one year in systolic blood pressure (placebo-subtracted difference -0.9 mm Hg), diastolic blood pressure (-0.8 mmHg), heart rate (-1.0 beat per minute), low-density lipoprotein cholesterol (-1.2 mg/dL), triglycerides (-11.7 mg/dL) and non-HDL cholesterol (-2.6 mg/dL). As a key secondary endpoint, 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%). 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. Additionally, hypoglycemia occurred in 3.9% of patients treated with BELVIQ versus 3.4% in those treated with placebo in the overall safety population. Severe hypoglycemia with serious complications was rare, but more common with BELVIQ versus placebo (0.2% vs. 0.1%), respectively.

“The CAMELLIA-TIMI 61 study found that in obese and overweight patients at high risk for a cardiovascular event, BELVIQ facilitated durable weight loss without an increased risk for major adverse cardiovascular events,” said Erin Bohula, MD, DPHIL cardiologist and staff investigator, TIMI Study Group, Brigham and Women’s Hospital. “These results, for the first time, showed the cardiovascular safety of a weight loss drug in a rigorous study.”

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

“We are pleased these results both fulfill our obligation to evaluate the long-term safety of our medicine, and also provide important new insights about long-term treatment with BELVIQ,” said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “We hope these new findings ultimately will inform care providers and patients, particularly those with cardiovascular-related complications, as they work together toward their weight management goals.”

Eisai and the TIMI Study Group will present additional results of the CAMELLIA-TIMI 61 study at the European Association for Study of Diabetes (EASD) Meeting in Berlin on October 4. With the results of this study, Eisai will have discussions with the U.S. FDA, including potential revision of the product label to include meaningful and important information for prescribers.

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 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 for the potential to delay or prevent 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+, consisting of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization due to unstable angina, heart failure or coronary revascularization. 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.

 Media Inquiries: Investor Inquiries: Michele Randazzo Alex Scott Eisai Inc. Eisai Inc. 201-746-2979 201-746-2177 michele_randazzo@eisai.com alex_scott@eisai.com 

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