The FDA approves Contrave(NB) for weight loss
In September 2014, the United States Food and Drug Administration(U.S. FDA) approved a new weight loss drug, Contrave, a novel combination product for the treatment of obesity composed of bupropion and naltrexone)hereafter called NB) developed by Orexigen.
Indications for Contrave: The treatment of obesity and weight management, including weight loss and maintenance of weight loss, used along with lifestyle modification.
Contrave is recommended for patients with an initial body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more risk factors (e.g. diabetes, dyslipidemia, sleep apnea, or hypertension).
Dosing of Contrave: The recommended daily dose of Contrave is two 8 mg naltrexone/90 mg bupropion (8/90) tablets taken twice daily for a total daily dose of 32 mg naltrexone/360 mg bupropion (32/360).
Assess Effectiveness of Contrave in 4 months: Most patients who respond to Contrave will have done so by 4 months of treatment. If a patient has not exhibited clinically meaningful weight loss (e.g., at least 5%) after 4 months of treatment, the physician should consider discontinuation of Contrave and initiation of other weight management strategies should be considered.
Dose Escalation of Contrave: Upon initiation, Contrave dosing should be escalated starting with one tablet taken daily for the first week, followed by the addition of another tablet each day during each subsequent week, until the total daily maintenance dose of two tablets twice a day (32/360) is reached at the start of Week 4.
Patients may experience elevated blood pressure or pulse during Contrave treatment; the risk may be greater during the initial 3 months of therapy. If clinically relevant and sustained (e.g., at least two consecutive measurements) increases in blood pressure or pulse occur, Contrave should be discontinued. As patients with hypertension or a history of hypertension may be at increased risk of blood pressure elevations, care should be exercised when initiating treatment with Contrave in such patients.
Studies in support of Contrave for weight loss
Achieving 5% weight loss is not only an FDA guidance efficacy benchmark, but this degree of weight loss is known to confer significant cardiometabolic benefit. Similarly, the Contrave trials demonstrated beneficial effects on prespecified weight-related cardiometabolic parameters, including:
- waist circumference,
- triglycerides, HDL-cholesterol,
- high-sensitivity C-reactive protein (hs-CRP),
- glycemic control (fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance [HOMA-IR], and, in patients with diabetes, hemoglobin A1c [HbA1c]),
- quality of life and control of eating.
All four Phase 3 studies showed statistically significant improvement in each co-primary endpoint relative to placebo. Contrave met the second benchmark for weight loss efficacy in three of the four studies.
How does Contrave work for weight loss?
Contrave (generally referred to as “NB” hereafter), a novel combination product for the treatment of obesity, is composed of bupropion (a relatively weak inhibitor of the neuronal uptake of norepinephrine [NE] and dopamine [DA]) combined with naltrexone (a mu-opioid receptor antagonist). Bupropion has been shown to stimulate hypothalamic pro-opiomelanocortin (POMC) neurons that release alpha -melanocyte stimulating hormone (α-MSH) which, in turn, binds to melanocortin 4 (MC4) receptors.
The binding of α-MSH to MC4 receptors initiates a cascade of actions that results in weight loss via reduced energy intake and increased energy expenditure (Cowley et al., 1999). When α-MSH is released, POMC neurons simultaneously release β-endorphin, an endogenous agonist of the mu-opioid receptor that mediates a negative feedback loop on POMC neurons leading to a decrease in the release of α-MSH (Cowley et al., 2001; Ibrahim et al., 2003; Kelly et al., 1990; Loose and Kelly, 1990). Blocking this inhibitory feedback loop with naltrexone is proposed to facilitate a more potent and longer-lasting activation of POMC neurons, thereby amplifying effects on energy balance. As a result, co-administration of bupropion and naltrexone produces a substantially greater effect on the POMC firing rate than either compound administered alone, suggesting that the drugs act synergistically.
Why do we need another weight loss drug?
Obesity is a rapidly growing epidemic among adults, adolescents, and children in the United States. Currently, there are three main approaches to the treatment of obesity:
(1) diet, physical activity, and behavioral modification (diet and exercise);
(2) pharmacotherapy; and
Diet and exercise is the mainstay of weight management and generally precedes other measures. Unfortunately, diet and exercise alone yield mostly limited and transient weight loss, with many individuals finding it difficult to adhere to such regimens. The strategy to implement pharmacotherapeutic or surgical approaches in addition to diet and exercise depends upon the patient’s BMI as well as the presence of obesity-related comorbidities.
However, unlike the situation for other metabolic diseases such as hypertension and type 2 diabetes, there are very limited obesity pharmacotherapies available. Although orlistat is approved for long-term use and provides efficacy beyond that usually achievable using diet and exercise alone, it is not tolerated well by some patients. The other available pharmacotherapies, e.g. phentermine, are approved for short-term use only. While more invasive options (e.g., gastric banding, bariatric surgery) do result in greater weight loss than is achievable with pharmacotherapy, these are targeted primarily to those patients with the highest BMI. The benefit of surgery is also offset by greater expense and risk. In the face of such limited options, patients often resort to the use of off-label medications or dietary supplements that may be ineffective or unsafe. In this context, agents such as NB may offer viable alternatives for many obese patients.
Contrave weight loss drug clinical studies
All four studies in the NB Phase 3 program demonstrated statistically significant and clinically meaningful weight loss following up to 56 weeks of treatment with NB32 (and NB16 in Study NB-301) compared with placebo.
The average percent weight loss from baseline observed with NB treatment across the four studies corresponded to between approximately 5 and 9 kg (11 to 22 pounds).
SAFETY OF CONTRAVE
The safety profile of NB was well characterized in a large clinical program that included 3475 NB treated patients overall and 2313 patient-years of experience, using primarily the proposed NB32 and NB16 daily doses. Data were integrated (pooled) across the 24-week primary efficacy period of Phase 2 study NB-201 and the four 56-week Phase 3 studies (NB-301, NB -302, NB-303, and NB-304) to create the Primary Dataset (N=1515 placebo patients; N=3239 NB patients), as these studies were all placebo-controlled and 6- to 12-months in duration. The observed NB safety and tolerability profile was generally comparable to the well-established safety profiles associated with naltrexone and bupropion, each with more than 20 years of post-marketing experience and approximately 1 million and more than 50 million unique exposures, respectively.1 The individual doses of naltrexone and bupropion in the NB combination were within or lower than the approved range of doses for the individual components. With the exception of nausea and vomiting, the NB combination of naltrexone and bupropion did not appear to be associated with increased adverse events (AEs) relative to the individual components.
Adverse Events/Side Effects of Contrave. The most commonly reported AEs (those that occurred at a ≥5% incidence in the Total NB group and greater than the incidence in the placebo group) for patients treated with Contrave.
Summary of Contrave for weight loss
The benefits of Contrave outweigh the risks given the clinically meaningful weight loss and improvement in multiple markers of cardiometabolic risk and patient-reported quality of life.
These benefits in aggregate are expected to be greater in general clinical practice, as proposed labeling would lead to discontinuation of treatment for patients not experiencing at least a 5% decrease from baseline in body weight. Benefits are observed across a range of overweight and obese patient subgroups and in various treatment settings.
Of note, the population of patients receiving currently approved bupropion-containing therapies has important similarities to patients enrolled in the Contrave clinical program, as well as the population of patients who receive currently marketed obesity pharmacotherapy.
In addition, clinical experience and investigation in relevant patient populations, including those with cardiovascular risk factors or established cardiovascular disease, have not identified specific safety signals for clinical cardiovascular events.
Overall, the Contrave safety profile is well-understood, with known risks that are predictable and manageable via appropriate risk mitigation approaches.
Orexigen is developing a plan for additional clinical studies to assess: 1) prescription utilization patterns, 2) physician and patient adherence to labeling, and 3) the impact of Contrave on cardiovascular outcomes. Takeida Pharmaceuticals distributes the medication in the United States.
Price of Contrave
The good news is that Contrave is one of the best priced new weight loss medications ever with the cost of a month supply of Contrave with insurance costing a maximum of $55.00(goes down to 45.00 after 2 months) and without insurance, a maximum of $70.00(goes down to 60.00 after 2 months) per month. This compares favorably with Qsymia that costs up to $150.00 per month and Belviq that costs up to $225.00 per month out of pocket without insurance.
Comparison of Contrave to other new weight loss medications
Comparing Contrave to the other weight loss medications based on the studies so far shows Contrave is somewhat in the middle in terms of weight loss results. The studies have shown Contrave is expected to lead to about 5% weight loss in a year for most people. Qsymia, a combination of Phentermine and Topiramate, is a bit more effective at 9% and Belviq is a bit less effective than Contrave at 3-4.5% although individual results may vary and further studies are needed to compare these medications head to head!
Locations for Contrave weight loss doctors
Contrave Doctor in Philadelphia, PA
Most W8MD Medical Weight Loss Centers offer Contrave, Belviq, Qsymia, Phentermine, Topiramate, Phendimetrazine, Diethylpropion and other weight loss medications when clinically appropriate after consultation with our medical weight loss physicians.
W8MD’s Philadelphia Insurance Weight Loss & Sleep Center: 1718, Welsh Rd, Philadelphia, PA, 19115 Ph: 1-215-676-2334
Contrave Doctor in King of Prussia, PA
W8MD’s King Of Prussia Weight Loss & Sleep Center: 987 Old Eagle School Rd, Ste 712, Wayne, PA, 19087 Ph: 215-676-2334
Contrave Doctor in New York City
W8MD’s NYC Insurance Weight Loss & Sleep Center: 2003, Bath Avenue, Brooklyn, NY, 11214 Ph: 1-718-946-5500.
Contrave Doctor, New Jersey
W8MD weight loss program in New Jersey
W8MD weight loss program at Vida Sleep Center of Dr. Felix Roque’s office at 543, 45th Street, Union City, New Jersey. 543 45th St, Union City, NJ 07087. Phone: (201) 766-6469. This center bills out of network for insurance.
Call W8MD today at 1-800-W8MD-007 to learn more. As a unique medical weight loss program that accepts health insurance with experienced and trained weight loss physicians, W8MD attracts patients from far and near including other states and sometimes even other countries!
Reviews of W8MD medical weight loss program on Yelp:
Wonderful doctor. Speaks to me with respect and great knowledge on weight loss. Fabulous results after 2 months, I’ve lost 30 pounds. Highly recommend. – Mike B.