SAN DIEGO, April 25, 2017 /PRNewswire/ -- Orexigen
Therapeutics, Inc. (Nasdaq: OREX), a biopharmaceutical company helping to improve the health and lives of patients struggling
with weight loss, today announced that Health
Canada has completed its screening phase and accepted for review a New Drug Submission for marketing approval of Contrave®
(naltrexone HCl and bupropion HCl). The regulatory submission was filed by Valeant Canada, an affiliate of Valeant
Pharmaceuticals International, Inc. If approved, Valeant will market and distribute Contrave in Canada as part of its distributorship agreement with Orexigen, executed in August 2016.
"We are excited about achieving this important step toward making Contrave available for patients in Canada," said Dr. Thomas Cannell, Chief Operating Officer and President of Global Commercial Products
of Orexigen. "We look forward to leveraging our strong alliance management capabilities to support Valeant's commercialization in
the Canadian market."
Under the terms of the agreement, Valeant is responsible for obtaining regulatory approval and for all commercialization
activity and expenses. Valeant expects to begin marketing Contrave in the first half of 2018, if regulatory approval is
obtained.
According to data from Statistics Canada, obesity and related comorbidities continue to be a growing problem in Canada, with almost two thirds of Canadian adults either overweight or struggling with obesity.
Estimates of the economic burden of obesity in Canada range from $4.6 billion to $7.1 billion annually.1
Orexigen has partnerships to commercialize Contrave and Mysimba® (naltrexone HCl / bupropion HCl prolonged release) in a total
of 39 countries worldwide, including partnerships with Valeant in Canada, Australia, New Zealand, South Africa and
21 European countries.
About Valeant Canada
Valeant Canada is an affiliate of Valeant Pharmaceuticals International Inc., a multinational specialty pharmaceutical company
that develops, manufactures, and markets a broad range of pharmaceutical products, primarily in the areas of dermatology, eye
health, cardio-metabolic, and neurology. More information about Valeant Canada can be found at www.valeantcanada.com.
About Orexigen Therapeutics
Orexigen Therapeutics, Inc. is a biopharmaceutical company focused on the treatment of obesity. Orexigen's first
product, Contrave® (naltrexone HCl and bupropion HCl extended release), was approved in the United
States in September 2014 and became the most prescribed branded obesity medication in
the United States in June 2015. In the European Union, the
drug has been approved under the brand name Mysimba® (naltrexone HCl/ bupropion HCl prolonged release). Orexigen is
undertaking a range of development and commercialization activities, both on its own and with strategic partners, to bring
Contrave / Mysimba to patients around the world. Further information about Orexigen can be found at www.orexigen.com .
About CONTRAVE
CONTRAVE, approved by the United States Food and Drug Administration in September 2014, is
indicated for use 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, type 2 diabetes mellitus or dyslipidemia). Further
information about Contrave can be found at www.contrave.com
.
The exact neurochemical effects of CONTRAVE leading to weight loss are not fully understood. CONTRAVE has two components:
naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and
norepinephrine. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain
involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit
(reward system).
Four 56-week multicenter, double-blind, placebo-controlled Phase 3 clinical trials were conducted to evaluate the effect of
CONTRAVE in conjunction with lifestyle modification in 4,536 subjects randomized to CONTRAVE or placebo. In these studies,
the most common adverse reactions (>5 percent) seen in patients taking CONTRAVE included nausea, constipation, headache,
vomiting, dizziness, insomnia, dry mouth and diarrhea.
Important Safety Information
WARNING: SUICIDAL THOUGHTS AND BEHAVIORS; AND NEUROPSYCHIATRIC REACTIONS
Suicidality and Antidepressant Drugs
CONTRAVE is not approved for use in the treatment of major depressive disorder or other psychiatric disorders. CONTRAVE
contains bupropion, the same active ingredient as some other antidepressant medications (including, but not limited to,
WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, and APLENZIN). Antidepressants increased the risk of suicidal thoughts and behavior in
children, adolescents, and young adults in short-term trials. These trials did not show an increase in the risk of suicidal
thoughts and behavior with antidepressant use in subjects over age 24; there was a reduction in risk with antidepressant use in
subjects aged 65 and older. In patients of all ages who are started on CONTRAVE, monitor closely for worsening, and for the
emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication
with the prescriber. CONTRAVE is not approved for use in pediatric patients.
Neuropsychiatric Reactions in Patients Taking Bupropion for Smoking Cessation
Serious neuropsychiatric reactions have occurred in patients taking bupropion for smoking cessation. The majority of these
reactions occurred during bupropion treatment, but some occurred in the context of discontinuing treatment. In many cases, a
causal relationship to bupropion treatment is not certain, because depressed mood may be a symptom of nicotine withdrawal.
However, some of the cases occurred in patients taking bupropion who continued to smoke. Although CONTRAVE is not approved for
smoking cessation, observe all patients for neuropsychiatric reactions. Instruct the patient to contact a healthcare provider if
such reactions occur.
Contraindications
CONTRAVE is contraindicated in: uncontrolled hypertension; seizure disorder or a history of seizures; use of other
bupropion-containing products; bulimia or anorexia nervosa, which increase the risk for seizure; chronic opioid or opiate agonist
(eg, methadone) or partial agonists (eg, buprenorphine) use, or acute opiate withdrawal; patients undergoing an abrupt
discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs; use during/within 14 days following treatment
with monoamine oxidase inhibitors (MAOIs)—there is an increased risk of hypertensive reactions when CONTRAVE is used
concomitantly with MAOIs and use with reversible MAOIs such as linezolid or intravenous methylene blue is also contraindicated;
known allergy to any component of CONTRAVE anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have been reported;
pregnancy.
WARNINGS AND PRECAUTIONS
Suicidal Behavior and Ideation
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely
for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of
drug therapy, or at times of dose changes, either increases or decreases. This warning applies to CONTRAVE because one of its
components, bupropion, is a member of an antidepressant class.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in
patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be
precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of
the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications,
both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of anxiety,
agitation, irritability, unusual changes in behavior, and other symptoms, as well as the emergence of suicidality, and to report
such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers.
Prescriptions for CONTRAVE should be written for the smallest quantity of tablets consistent with good patient management, in
order to reduce the risk of overdose.
Neuropsychiatric Symptoms and Suicide Risk in Smoking Cessation Treatment
CONTRAVE is not approved for smoking cessation treatment, but serious neuropsychiatric symptoms have been reported in patients
taking bupropion for smoking cessation. These have included changes in mood (including depression and mania), psychosis,
hallucinations, paranoia, delusions, homicidal ideation, hostility, agitation, aggression, anxiety, and panic, as well as
suicidal ideation, suicide attempt, and completed suicide. Observe patients for the occurrence of neuropsychiatric reactions.
Instruct patients to contact a healthcare professional if such reactions occur.
Seizures
CONTRAVE can cause seizures. The risk of seizure is dose-related. Discontinue treatment and do not restart CONTRAVE in
patients who experience a seizure. Caution should be used when prescribing CONTRAVE to patients with predisposing factors that
may increase the risk of seizure, including: history of head trauma or prior seizure, severe stroke, arteriovenous malformation,
central nervous system tumor or infection, or metabolic disorders (eg, hypoglycemia, hyponatremia, severe hepatic impairment, and
hypoxia); excessive use of alcohol or sedatives, addiction to cocaine or stimulants, or withdrawal from sedatives; patients with
diabetes treated with insulin and/or oral diabetic medications (sulfonylureas and meglitinides) that may cause hypoglycemia;
concomitant administration of medications that may lower the seizure threshold, including other bupropion products,
antipsychotics, tricyclic antidepressants, theophylline, systemic steroids.
Clinical experience with bupropion suggests that the risk of seizure may be minimized by adhering to the recommended dosing
recommendations, in particular: the total daily dose of CONTRAVE does not exceed 360 mg of the bupropion component (ie, four
tablets per day); the daily dose is administered in divided doses (twice daily); the dose is escalated gradually; no more than
two tablets are taken at one time; coadministration of CONTRAVE with high-fat meals is avoided; if a dose is missed, a patient
should wait until the next scheduled dose to resume the regular dosing schedule.
Patients Receiving Opioid Analgesics
Vulnerability to Opioid Overdose: CONTRAVE should not be administered to patients receiving chronic opioids, due to the
naltrexone component, which is an opioid receptor antagonist. If chronic opiate therapy is required, CONTRAVE treatment should be
stopped. In patients requiring intermittent opiate treatment, CONTRAVE therapy should be temporarily discontinued and lower doses
of opioids may be needed. Patients should be alerted that they may be more sensitive to opioids, even at lower doses, after
CONTRAVE treatment is discontinued. An attempt by a patient to overcome any naltrexone opioid blockade by administering large
amounts of exogenous opioids is especially dangerous and may lead to a fatal overdose or life-threatening opioid intoxication
(eg, respiratory arrest, circulatory collapse). Patients should be told of the serious consequences of trying to overcome the
opioid blockade.
Precipitated Opioid Withdrawal: An opioid-free interval of a minimum of 7 to 10 days is recommended for patients
previously dependent on short-acting opioids, and those patients transitioning from buprenorphine or methadone may need as long
as two weeks. Patients should be made aware of the risks associated with precipitated withdrawal and encouraged to give an
accurate account of last opioid use.
Increase in Blood Pressure (BP) and Heart Rate (HR)
CONTRAVE can cause an increase in systolic BP, diastolic BP, and/or resting HR. These events were observed in both patients
with and without evidence of preexisting hypertension. In clinical practice with other bupropion-containing products,
hypertension, in some cases severe and requiring acute treatment, has been reported. Blood pressure and pulse should be measured
prior to starting therapy with CONTRAVE and should be monitored at regular intervals consistent with usual clinical practice,
particularly among patients with cardiac or cerebrovascular disease and/or with controlled hypertension prior to treatment.
Allergic Reactions
Anaphylactoid/anaphylactic reactions and symptoms suggestive of delayed hypersensitivity have been reported with bupropion, as
well as rare spontaneous reports of erythema multiforme, Stevens-Johnson syndrome, and anaphylactic shock. Instruct patients to
discontinue CONTRAVE and consult a healthcare provider if they develop an allergic or anaphylactoid/anaphylactic reaction (eg,
skin rash, pruritus, hives, chest pain, edema, or shortness of breath) during this treatment.
Hepatotoxicity
Cases of hepatitis, clinically significant liver dysfunction, and transient asymptomatic hepatic transaminase elevations have
been observed with naltrexone exposure. Patients should be warned of the risk of hepatic injury and advised to seek medical
attention if they experience symptoms of acute hepatitis. CONTRAVE should be discontinued in the event of symptoms/signs of acute
hepatitis.
Activation of Mania
Bupropion, a component of CONTRAVE, is a drug used for the treatment of depression. Antidepressant treatment can precipitate a
manic, mixed, or hypomanic episode. The risk appears to be increased in patients with bipolar disorder or who have risk factors
for bipolar disorder. Prior to initiating CONTRAVE, screen patients for history of bipolar disorder and the presence of risk
factors for bipolar disorder (eg, family history of bipolar disorder, suicide, or depression). CONTRAVE is not approved for use
in treating bipolar depression.
Angle-Closure Glaucoma
The pupillary dilation that occurs following use of many antidepressant drugs, including bupropion, may trigger an
angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
Hypoglycemia with Use of Antidiabetic Medications
Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or
insulin secretagogues (eg, sulfonylureas). Measurement of blood glucose levels prior to starting CONTRAVE and during CONTRAVE
treatment is recommended in patients with type 2 diabetes. Decreases in medication doses for antidiabetic medications which are
non-glucose-dependent should be considered to mitigate the risk of hypoglycemia.
Adverse Reactions
Most common adverse reactions (≥5%) include: nausea (32.5%), constipation (19.2%), headache (17.6%), vomiting (10.7%),
dizziness (9.9%), insomnia (9.2%), dry mouth (8.1%), and diarrhea (7.1%).
Drug Interactions
Increased risk of hypertensive reactions can occur when CONTRAVE is used concomitantly with MAOIs. Use caution and consider
dose reduction of drugs metabolized by CYP2D6 when using with CONTRAVE. Avoid concomitant use with CYP2B6 inducers. Reduce
CONTRAVE dose when taken with CYP2B6 inhibitors. Dose CONTRAVE with caution when used with drugs that lower seizure threshold.
Use caution and monitor for CNS toxicity when using CONTRAVE concomitantly with dopaminergic drugs (levodopa and amantadine).
CONTRAVE can cause false positive urine test results for amphetamines.
Indication
CONTRAVE 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, type
2 diabetes mellitus, or dyslipidemia)
Limitations of Use
The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established. The safety and effectiveness of
CONTRAVE in combination with other products intended for weight loss, including prescription drugs and over-the-counter drugs,
and herbal preparations, have not been established.
Please see accompanying full Prescribing Information and Medication Guide for CONTRAVE.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
CONTRAVE® is a trademark of Orexigen Therapeutics, Inc. registered with the U.S. Patent and Trademark Office. All other
trademarks are the property of their respective owners.
Forward-Looking Statements
Orexigen cautions you that statements included in this press release that are not a description of historical facts are
forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "should,"
"intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward-looking
statements. These statements are based on our current beliefs and expectations. These forward-looking statements include
statements regarding: the potential for and timing of regulatory approval and commercialization of Contrave in Canada; and the potential for Valeant to be an ideal partner for Contrave in Canada. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen
that any of its plans will be achieved. Actual results may differ materially from those expressed or implied in this release due
to the risk and uncertainties inherent in the Orexigen business, including, without limitation: the potential that the marketing
and commercialization of Contrave will not be successful, particularly in the U.S.; the capabilities of our existing distribution
partners and the ability to obtain partnerships and marketing authorizations globally; competition in the global obesity market,
particularly from existing therapies; additional analysis of the interim results or the final data from the terminated Light
Study, including safety-related data, and the additional CVOT may produce negative or inconclusive results, or may be
inconsistent with the conclusion that the interim analysis was successful; our ability to retain ownership of Contrave and
Mysimba and create value in certain markets outside of the United States; our ability to
adequately inform consumers about Contrave; our ability to successfully commercialize Contrave with a specialty sales force in
the United States; our ability to obtain and maintain global intellectual property protection
for Contrave and Mysimba; legal or regulatory proceedings against Orexigen, as well as potential reputational harm, as a result
of misleading public claims about Orexigen; the therapeutic and commercial value of Contrave; our ability to successfully
acquire, develop and market additional product candidates or approved products; our ability to maintain sufficient capital to
fund our operations for the foreseeable future; estimates of the capacity of manufacturing and other facilities to support
Contrave; the potential for a Delaware court to determine that one or more of the patents are
not valid or that Actavis' proposed generic product is not infringing each of the patents at issue; and other risks described in
Orexigen's filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these
forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update
this news release to reflect events or circumstances after the date hereof, except as required by law. Further information
regarding these and other risks is included under the heading "Risk Factors" in Orexigen's Quarterly Report on Form 10-K filed
with the Securities and Exchange Commission on March 30, 2017 and its other reports, which are
available from the SEC's website (www.sec.gov) and on Orexigen's
website (www.orexigen.com) under the heading "Investors."
All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe
harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.
SOURCE Orexigen Therapeutics, Inc.
References:
-
Obesity in Canada: A Whole-of-Society Approach for a Healther Canada – Report of the Standing Senate Committee on
Social Affairs, Science and Technology Date accessed: 29 March 2016
Orexigen Contacts:
Jason Keyes
Chief Financial Officer
Orexigen Therapeutics, Inc.
+1-858-875-8600
jkeyes@orexigen.com
Erika Hackmann
Y&R PR (Media Contact for Orexigen)
+1-917-538-3375
erika.hackmann@yr.com
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SOURCE Orexigen Therapeutics, Inc.