FDA Accepts Eisai’s Supplemental New Drug Application (sNDA) to Update the Labeling for Anti-Obesity Agent BELVIQ® (lorcaserin HCl)

WOODCLIFF LAKE, N.J., Feb. 25, 2019 /PRNewswire/ -- Eisai Inc. announced today that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) to potentially update the label for BELVIQ^® (lorcaserin HCl) CIV 10 mg twice-daily/BELVIQ XR (lorcaserin HCl) CIV once daily to include long-term efficacy and safety data from CAMELLIA-TIMI 61, a clinical trial of BELVIQ in 12,000 overweight and obese patients with cardiovascular (CV) disease and/or multiple CV risk factors such as type 2 diabetes mellitus (T2DM).

The addition of this data has the potential for a revision to the product label’s Indications and Usage, removing the Limitation of Use related to the effect of BELVIQ on CV morbidity and mortality.

As previously reported and published in the New England Journal of Medicine on August 26th, CAMELLIA-TIMI 61 met its primary safety objective, 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 (HR 0.99; 95% CI: 0.85 to 1.14; p<0.001). Since the study met the primary safety endpoint for non-inferiority for MACE, the study continued to assess for the primary efficacy endpoint of whether or not BELVIQ reduced the incidence of major CV events compared to placebo for a broader composite endpoint, MACE+, consisting of CV 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.

“This sNDA file acceptance brings us one step closer to potentially incorporating data into our label based on the first completed large-scale cardiovascular outcomes trial for a weight loss agent,” said Lynn Kramer, M.D., Chief Clinical Officer and Chief Medical Officer, Neurology Business Group, Eisai. “We are excited about our data as it showed BELVIQ did not increase the incidence of MACE and look forward to continuing our discussions with the FDA.”

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. A total of 12,000 patients underwent randomization.

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 approximately 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 trial would continue to assess for the primary efficacy objective which 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 incidence of obesity in the U.S. has risen over 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 with obesity becoming 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.

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SOURCE Eisai Inc.