Contrave® (naltrexone HCI / bupropion HCI): North American Rights Licensed to Takeda Pharmaceuticals
Orexigen has licensed U.S. rights to Contrave to Takeda Pharmaceutical Company. Under the terms of the original September 2010 collaboration agreement, the Company received from Takeda a nonrefundable upfront cash payment of $50.0 million, and in the fourth quarter of 2014 Orexigen received additional payments totaling $100.0 million that was achieved between the execution of the collaboration agreement and the first commercial sale of Contrave in the United States. Takeda is responsible for all commercial activities and related expenses. Orexigen is eligible to receive tiered royalty payments ranging from a minimum of 20% to a maximum of 35%, subject to customary reductions, on increasing levels of net sales in the United States. Orexigen is eligible to receive $45 million in anniversary milestone payments through 2017, as well as additional payments of over $880 million upon achieving certain sales-based milestones.
In July 2015, Orexigen and Takeda amended and restated the collaboration agreement. The Restated Collaboration Agreement is substantially the same as the prior agreement subject to the following key changes. Full rights to Canada and Mexico have been returned to Orexigen. Orexigen is responsible for the cost of the cardiovascular outcomes clinical trial (the “CVOT”) to be conducted by Takeda up to the currently-projected total cost of the trial, above which the parties will generally share the costs equally. Takeda and the Company will be responsible for 75% and 25% of expenses, respectively, of any other post-approval development costs, including all other post-marketing requirement studies other than the CVOT. The Company is also eligible to receive up to an additional $105 million of potential milestone payments upon achievement of a combination of factors related to superiority claims reflected in approved labeling for Contrave, a lack of generic competition and net sales.
Contrave Korean Distributorship Agreement with Kwang Dong Pharmaceutical Company
In August 2015, Orexigen’s wholly-owned subsidiary Orexigen Therapeutics Ireland Ltd. and Kwang Dong Pharmaceutical Company, Ltd. executed a distributorship agreement for South Korea for Contrave® (naltrexone HCl / bupropion HCl extended release) monotherapy for weight management in overweight or obese adult patients. Under the terms of the agreement, Kwang Dong will be responsible for seeking regulatory approval and for all commercialization activity and expenses. Orexigen will supply Contrave tablets to Kwang Dong for a $7 million upfront payment, approximately 35 – 40% of net sales, potential sales-based milestone payments, and other fees. Kwang Dong expects to begin marketing Contrave in the second half of 2016, if regulatory approval is obtained.
Naltrexone HCl /bupropion HCl: Rest-of-World Rights
Outside the United States and Korea, Orexigen retains all rights to naltrexone HCl /bupropion HCl (branded as Mysimba™ in the European Union) and is pursuing pharmaceutical partnerships to support rest-of-world development and commercialization.
Important Safety Information for Contrave
CONTRAVE can cause serious side effects of suicidal thoughts or actions. One of the ingredients in CONTRAVE is bupropion HCl. Bupropion has caused some people to have suicidal thoughts or actions or unusual changes in behavior, whether or not they are taking medicines used to treat depression. Bupropion may increase suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. If you already have depression or other mental illnesses, taking bupropion may cause it to get worse, especially within the first few months of treatment.
Do not take CONTRAVE if you:
Stop taking CONTRAVE and call a healthcare provider right away if you, or your family member, have any of the following symptoms, especially if they are new, worse, or worry you: thoughts about suicide or dying; attempts to commit suicide; depression; anxiety; feeling very agitated or restless; panic attacks; trouble sleeping (insomnia); irritability; acting aggressive, being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking (mania); other unusual changes in behavior or mood.
While taking CONTRAVE, you or your family members should pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings and maintain communication with your healthcare provider. CONTRAVE has not been studied in and is not approved for use in children under the age of 18.
Tell your healthcare provider about all of your medical conditions
- Have uncontrolled high blood pressure
- Have or have had seizures
- Use other medicines that contain bupropion such as WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, and APLENZIN
- Have or have had an eating disorder called anorexia or bulimia
- Are dependent on opioid pain medicines or use medicines to help stop taking opioids such as methadone or buprenorphine, or are in opiate withdrawal
- Drink a lot of alcohol and abruptly stop drinking, as this may increase your chance of having a seizure; or use medicines called sedatives (these make you sleepy), benzodiazepines, or anti-seizure medicines and you stop using them all of a sudden
- Have taken medicines called monoamine oxidase inhibitors (MAOIs), including linezolid, within the last 14 days
- Are allergic to naltrexone HCl or bupropion HCl or any of the ingredients in CONTRAVE
- Are pregnant or planning to become pregnant. Tell your healthcare provider right away if you become pregnant while taking CONTRAVE
, especially: depression or other mental illnesses; attempted suicide; seizures; head injury; tumor or infection of your brain or spine; low blood sugar or low levels of sodium in your blood; liver or kidney problems; high blood pressure; heart problems or stroke; eating disorder. Also tell your doctor if you drink a lot of alcohol and plan to suddenly stop; abuse prescription medicines or street drugs; are over the age of 65; have any other medical conditions; or are breastfeeding or plan to breastfeed.
Tell your healthcare provider about all the medicines you take
including prescription and over-the-counter medicines, vitamins, and herbal supplements. Do not take any other medicines while you are taking CONTRAVE unless your healthcare provider has said it is okay to take them
Swallow CONTRAVE tablets whole. Do not cut, chew, or crush CONTRAVE tablets
. Tell your healthcare provider if you cannot swallow CONTRAVE tablets whole. Do not
take CONTRAVE with high-fat meals. It may increase your risk of seizures. Take CONTRAVE exactly as prescribed.
Possible serious side effects of CONTRAVE:
- If you have a seizure, stop taking CONTRAVE, tell your healthcare provider right away, and do not take CONTRAVE again
- If you take opioid medicines, there may be a risk of opioid overdose. You should get emergency medical help right away if you have trouble breathing; become drowsy with slowed breathing; have slow, shallow breathing; or feel faint, dizzy, or confused
- Sudden opioid withdrawal can be severe and may require hospitalization
- Stop taking CONTRAVE and get medical help immediately if you have any of the following signs and symptoms of severe allergic reactions: rash, itching, hives, fever, swollen lymph glands, painful sores in your mouth or around your eyes, swelling of your lips or tongue, chest pain, or trouble breathing
- Increases in blood pressure or heart rate may occur
- CONTRAVE can cause liver damage or hepatitis. Stop taking CONTRAVE if you have any of the following symptoms of liver problems: stomach area pain lasting more than a few days, dark urine, yellowing of the whites of your eyes, or tiredness
- Manic episodes can occur. CONTRAVE can cause some people who were manic or depressed in the past to become manic or depressed again
- CONTRAVE can cause visual problems (angle-closure glaucoma). Signs and symptoms may include: eye pain, changes in vision, swelling or redness in or around the eye. Talk with your doctor to find out if you are at risk and to get treatment to prevent it
- Increased risk of low blood sugar (hypoglycemia) in people with type 2 diabetes mellitus who also take medicines to treat their diabetes (such as insulin or sulfonylureas). You should check your blood sugar before you start and while taking CONTRAVE
The most common side effects of CONTRAVE include nausea, constipation, headache, vomiting, dizziness, trouble sleeping, dry mouth, and diarrhea.
Tell your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of CONTRAVE.
Use of CONTRAVE
CONTRAVE is a prescription medicine that contains 2 medicines (naltrexone HCl and bupropion HCl) that may help some obese adults*, or overweight adults who also have weight-related medical problems†, lose weight and keep the weight off.
*Body mass index (BMI) of 30 kg/m2 or greater.
- CONTRAVE should be used with a reduced calorie diet and increased physical activity
- It is not known if CONTRAVE changes your risk of heart problems or stroke or of death due to heart problems or stroke
- It is not known if CONTRAVE is safe and effective when taken with other prescription, over-the-counter, or herbal weight loss products
†BMI of 27 kg/m2 or greater with at least one weight-related medical problem such as high blood pressure, high cholesterol, or type 2 diabetes.
Talk to your healthcare provider. Please see accompanying Full Prescribing Information, including Medication Guide, for CONTRAVE.
You are encouraged to report negative side effects of prescription drugs to the FDA.
or call 1-800-FDA-1088.