New data in adults with obesity or who are overweight with comorbidities losing at least 5% body weight with Saxenda® (liraglutide [rDNA origin] injection) showed improvement in blood glucose, CV risk factors and quality of life outcomes

News provided by

Mar 07, 2015, 04:00 ET

SAN DIEGO, March 7, 2015 /PRNewswire/ -- Today, new data from the phase 3a SCALE™ Obesity and Pre-diabetes trial were presented at The Endocrine Society's 97^th Annual Meeting (ENDO), showing that adults with obesity or who are overweight with comorbidities who had lost ≥5% of their body weight at 56 weeks (i.e., weight loss responders), demonstrated greater improvements across a range of efficacy outcomes with Saxenda^® (liraglutide [rDNA origin] injection) treatment in combination with a reduced-calorie diet and increased physical activity, compared with those that had a weight loss of <5% (i.e., non-responders).¹

In the SCALE™ Obesity and Pre-diabetes trial, 63.2% of adults achieved a clinically meaningful body weight reduction of at least 5% with Saxenda^® compared with 27.1% on placebo (P<0.0001). The average weight loss for responders on Saxenda^® treatment was 11.7% compared with 1.7% for non-responders. For placebo treatment, average weight loss in responders was 10.0% versus 0.1% weight gain in non-responders. Saxenda^® treatment was associated with a greater reduction in waist circumference in responders, compared with non-responders (11.0 cm vs. 3.3 cm).¹

In addition to weight loss, improvements across a number of secondary endpoints were also observed in the responder population (Saxenda^® and placebo). A greater improvement was seen in fasting plasma glucose (FPG) in Saxenda^® responders compared with placebo responders (-8.3 vs. -2.8 mg/dl, respectively) as well as non-responders (-5.0 vs. +1.1 mg/dl, respectively). In addition, treatment with Saxenda^® was associated with a greater reduction in systolic blood pressure (SBP) compared with placebo in both responders (-5.5 vs. -3.4 mm Hg, respectively) and non-responders (-2.0 vs. -0.8 mm Hg, respectively). Improvements in physical health scores (as measured by the SF-36 questionnaire) were seen with Saxenda^® and placebo responders (+4.3 vs. +4.1 points, respectively) compared with non-responders (+2.1 vs. +1.3 points, respectively).¹

"These are important findings as they show that for adults with obesity or who are overweight with comorbidities, losing 5% to 10% of their body weight can help improve comorbidities, including fasting plasma glucose and blood pressure," said Dr. Patrick O'Neil, Professor of Psychiatry and Behavioral Sciences at the Medical University of South Carolina and SCALE™ clinical trial investigator. "Those who responded, losing 5% or more of their body weight, not only saw improvements in cardiometabolic risk factors but also in quality of life outcomes, compared with those who did not respond, for both liraglutide and placebo treatment."

Across the SCALE™ clinical development program, Saxenda^® (liraglutide [rDNA origin] injection) was generally well tolerated. The most common side effects observed were related to the gastrointestinal system.² In the SCALE™ Obesity and Pre-diabetes trial, rates of adverse events were similar in both responders and non-responders. The number of adverse events leading to trial withdrawal was lower in responders compared with non-responders.¹

Indications and Usage

Saxenda^® (liraglutide [rDNA origin] injection) is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adult patients 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, type 2 diabetes mellitus, or dyslipidemia).

Limitations of Use

Saxenda^® is not indicated for the treatment of type 2 diabetes.
Saxenda^® should not be used in combination with any other GLP-1 receptor agonist.
Saxenda^® should not be used with insulin.
The effects of Saxenda^® on cardiovascular morbidity and mortality have not been established.
The safety and efficacy of coadministration with other products for weight loss have not been established.
Saxenda^® has not been studied in patients with a history of pancreatitis.

For full prescribing information, please go to www.Saxenda.com.

Important Safety Information

WARNING: RISK OF THYROID C-CELL TUMORS
Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. It is unknown whether Saxenda^® causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined. Saxenda^®(liraglutide [rDNA origin] injection) is contraindicated in patients with a personal or family history of MTC and in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the risk of MTC with use of Saxenda^® and inform them of symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with Saxenda^®.

Contraindications
Saxenda^®is contraindicated in the following conditions:

Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components
Pregnancy

Warnings and Precautions

Acute Pancreatitis: Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of Saxenda^® observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, Saxenda^® should promptly be discontinued and appropriate management should be initiated. If pancreatitis is confirmed, Saxenda^® should not be restarted.
Acute Gallbladder Disease: Substantial or rapid weight loss can increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in Saxenda^®-treated patients than in placebo-treated patients even after accounting for the degree of weight loss. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
Serious Hypoglycemia: When Saxenda^® is used with an insulin secretagogue (e.g., a sulfonylurea) serious hypoglycemia can occur. Consider lowering the dose of the insulin secretagogue to reduce the risk of hypoglycemia.
Heart Rate Increase: For patients who experience a sustained increase in resting heart rate while taking Saxenda^®, Saxenda^® should be discontinued.
Renal Impairment: Renal impairment has been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration, which may sometimes require hemodialysis. Use caution when initiating or escalating doses of Saxenda^® in patients with renal impairment.
Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis and angioedema) have been reported during postmarketing use of liraglutide. If symptoms of hypersensitivity reactions occur, patients must stop taking Saxenda^® and promptly seek medical advice.
Suicidal Behavior and Ideation: Patients treated with Saxenda^® should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Saxenda^® in patients who experience suicidal thoughts or behaviors. Avoid Saxenda^® in patients with a history of suicidal attempts or active suicidal ideation.

Adverse Events

The most common adverse reactions, reporting in ≥5% are: nausea, hypoglycemia, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and increased lipase.

Use in Specific Populations

Nursing mothers should either discontinue Saxenda^® (liraglutide [rDNA origin] injection) or discontinue nursing.
Safety and effectiveness of Saxenda^® have not been established in pediatric patients and is not recommended for use in pediatric patients.

About obesity
Obesity is a disease that requires chronic management.^3-5 It is associated with serious comorbidities including type 2 diabetes, heart disease, obstructive sleep apnea (OSA), certain types of cancer and a decreased life expectancy.^6-8 The risk of morbidity and mortality increases with the severity of obesity.^8,9 It is a complex and multifactorial disease that is influenced by genetic, physiological, environmental and psychological factors.¹⁰

The global increase in the prevalence of obesity is a public health issue that has severe cost implications to healthcare systems.^11,12 In 2011-2012 in the U.S., approximately 35% of adults, or nearly 80 million adults, lived with obesity.¹³

About Saxenda^®
Saxenda^® is a once-daily glucagon-like peptide-1 (GLP-1) analog with 97% similarity to naturally occurring human GLP-1, a hormone that is released in response to food intake.² Like human GLP-1, Saxenda^® regulates appetite and lowers body weight through decreased food intake. As with other GLP-1 receptor agonists, liraglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. These effects can lead to a reduction of blood glucose. Saxenda^® was evaluated in the SCALE™ (Satiety and Clinical Adiposity−Liraglutide Evidence in Nondiabetic and Diabetic people) phase 3 clinical trial program, which involved more than 5,000 study participants who have obesity (BMI ≥30 kg/m² ) or who are overweight (BMI ≥27 kg/m² ) with comorbidities.²

Saxenda^® was approved by the FDA on December 23, 2014, as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥30 kg/m²) or who are overweight (BMI ≥27 kg/m²) with at least one weight-related comorbidity.¹⁴

Saxenda^® received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on January 22, 2015. In accordance with the EMA Centralised Procedure, a decision whether to grant marketing authorization is taken by the European Commission within approximately 2 to 3 months.¹⁴

About SCALE™ Obesity and Pre-diabetes
The SCALE™ Obesity and Pre-diabetes trial is a randomized, double-blind, placebo-controlled, multinational trial in non-diabetic adults with obesity and non-diabetic adults who are overweight with comorbidities. There were 3,731 participants randomized to treatment with Saxenda^® (liraglutide [rDNA origin] injection) or placebo in combination with reduced-calorie diet and increased physical activity.² In addition, participants were further stratified to 56 weeks or 160 weeks of treatment based on pre-diabetes status at baseline screening.¹⁴

The objectives of this trial were to demonstrate clinically meaningful weight loss at 56 weeks, as well as to investigate the long-term potential efficacy of Saxenda^® to delay the onset of type 2 diabetes in participants with pre-diabetes at baseline screening.¹⁵

It is the largest of the phase 3a trials in the SCALE™ clinical development program, which encompassed more than 5,000 adults with obesity or adults who are overweight with comorbidities.¹⁴

About Novo Nordisk
Headquartered in Denmark, Novo Nordisk is a global healthcare company with more than 90 years of innovation and leadership in diabetes care. The company also has leading positions within hemophilia care, growth hormone therapy and hormone replacement therapy. Novo Nordisk employs approximately 41,000 employees in 75 countries, and markets its products in more than 180 countries. For more information, visit novonordisk.com, Facebook, Twitter, LinkedIn, YouTube

Further information
Media:
Katrine Sperling	+45 4442 6718	[email protected]
Sharon Corbitt (US)	+1 609 578 9974	[email protected]

Investors:
Kasper Roseeuw Poulsen	+45 3079 4303	[email protected]
Jannick Lindegaard Denholt	+45 3079 8519	[email protected]
Daniel Bohsen	+45 3079 6376	[email protected]
Frank Daniel Mersebach (US)	+1 609 235 8567	[email protected]

References

1	O'Neil P, Fujioka K, Violante Ortiz R, Claudius B, Jensen CB, Astrup A. Efficacy and safety of liraglutide 3.0 mg in adult overweight and obese weight loss responders without diabetes: the SCALE™ obesity and pre-diabetes, a randomized, double-blind and placebo-controlled trial. Paper presented at: ENDO 2015, The Endocrine Society's 97th Annual Meeting (ENDO). March 5-8, 2015; San Diego, CA.
2	Saxenda [prescribing information]. Plainsboro, NJ:Novo Nordisk Inc; 2015.
3	American Medical Association. Business of the American Medical Association House of Delegates 2013 Annual Meeting annotated reference committee reports: reference committee D. http://www.ama-assn.org/assets/meeting/2013a/a13-addendum-refcomm-d.pdf. Approved June 8, 2014. Accessed September 8, 2014.
4	Mechanick JI, Garber AJ, Handelsman Y, Garvey WT. American Association of Clinical Endocrinologists' position statement on obesity and obesity medicine. Endocr Pract. 2012;18(5):642-648.
5	Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. J Am Coll Cardiol. 2014;63(25_PA):2985-3023.
6	Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of comorbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9(88):1471-2458.
7	Gami AS, Caples SM, Somers VK. Obesity and obstructive sleep apnea. Endocrinol Metab Clin North Am. 2003;32(4):869-894.
8	Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003;138(1):24-32.
9	Bray GA, Bellanger T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine. 2006;29(10):109-117.
10	Wright SM, Aronne LJ. Causes of obesity. Abdom Imaging. 2012; 37(5):730-732.
11	World Health Organization. Fact sheet no. 311: obesity and overweight. http://www.who.int/mediacentre/factsheets/fs311/en/. Updated August 2014. Accessed August 11, 2014.
12	Cawley J, Meyerhoefer C. The medical care costs of obesity: an instrumental variables approach. J Health Economics. 2012;31(1):219-230.
13	Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814.
14	Data on file. Novo Nordisk Inc; Plainsboro, NJ.
15	Novo Nordisk A/S. Effect of liraglutide on body weight in non-diabetic obese subjects or overweight subjects with co-morbidities: SCALE obesity and pre-diabetes. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2015 Feb 5]/ Available from: https://clinicaltrials.gov/ct2/show/NCT01272219 Identifier: NCT01272219.