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.