Your informational guide to Tesofensine
One of the other medications for obesity that is going through trial stages of testing is one called Contrave® its manufacturer is Orexigen Therapeutics Inc. But interestingly it is actually just a combination of two already approved and existing drugs for other ailments. These already existing medications are the antidepressant Wellbutrin® (or also known as bupropion which has also been used as a smoking cessation). The other is a drug they use for addictions (primarily alcohol, street drugs etc) named Revia® or Vivitrol® or generic name Naltrexone. During phase 2 testing different dosages where used in a once daily formula these include:
(16 mg naltrexone *IR - 400 mg bupropion *SR)
(32 mg naltrexone *IR - 400 mg bupropion *SR)
(48 mg naltrexone *IR - 400 mg bupropion *SR)
*IR= Immediate Release
The (32 mg naltrexone *IR / 400 mg bupropion *SR) on average showed the best benefit to risk ratio thus making it a favorite.
However it should be noted that the actual Contrave® being used in phase 3 trials, and is most likely the one to be used, has an Orexigen developed naltrexone SR to make the drug more tolerable. Contrave® = (naltrexone SR / Bupropion SR)
In other testing back in June of 2007 Orexigen announced that after reviewing information from a phase 2 trial test with Contrave that patients demonstrated a 50% decrease in metabolic syndrome. Metabolic syndrome is a group of related disorders that increase the risk of developing metabolic/cardiovascular problems. These include things like high blood pressure, high insulin levels excess fat specifically around the waist etc. These can lead to a risk of developing diabetes and other weight related health problems.
After the 24 week period of testing Contrave for obesity it was pointed out that of the 31% of the people who had metabolic syndrome, 16% no longer experienced it. The patients on the placebo also had a decrease but a very minimal amount, their numbers went from 38% to 30%.
Contrave works in the brain or hypothalamus where the control center for ones appetite is. Some people have seen decent weight loss with bupropion alone, but the combination is where the benefits of weight loss really get underway. And the fact that bupropion alone has not been FDA approved to be prescribed as a weight loss drug. In tests with a placebo + naltrexone, a placebo + bupropion, Contrave out did both. There have been clinical trials that have shown its effectiveness of Contrave including the phase 3 testing where more than 4500 patients going above the FDA's efficacy benchmark for clinically significant weight loss.
On average, the participants lost between 9% to 15% of their body weight (in conjunction with the overall test that included some diet restrictions and exercise). This was much better than the patients that where in the placebo group. And according to the FDA, that constitutes as an amount that would allow it to be considered as a potentially approved obesity drug based on that finding alone. But these findings also come with some side effects for some of its users.
Some of the potential side effects reported are mild to moderate nausea, some mid to moderate headaches and constipation some of which weakened, or disappeared after further use. This does not mean that Contrave is on its way to become approved. When and if Contrave is presented to the FDA for approval, the FDA will consider many different factors in its decision of approval or not. Some concerns are things like cardiovascular safety, and psychological issues.
July 21st, 2009
Orexigen announced that all three remaining phase 3 trials testing Contrave met their endpoints.
Dec 17th, 2009
News out that Orexigen Therapeutics plan on bringing Contrave before the FDA within months...
Jan 13th, 2010
Orexigen Therapeutics Inc, is currently in talks with some potential partners to help market the drug Contrave but stated today they are willing to go it alone if no suitable partner if found and are comfortable doing so. Contrave is expected to be submitted to the FDA for approval sometime early this year.
March 9th, 2010
Orexigen Therapeutics plans to file Contrave to the FDA for potential approval by the end of April.
March 12th, 2010
Orexigen Therapeutics have signed a deal with Canadian drug maker Patheon to be the manufacturer of it. The FDA decision date is at approximately February 2011.
March 31st, 2010
Today Orexigen Therapeutics submitted its Investigational Obesity Drug Contrave to the FDA for approval. Also known as a NDA (New Drug Approval) Orexigen believes it covers all areas the FDA requires for a drug to be considered under a weight loss and weight maintenance medication.
April 13th, 2010
Today Orexigen reported that Contrave was less effective than earlier reported. But still well within the FDA's guidelines for a medication to be considered as an obesity reducing drug. The errors are as follows: After 56 weeks of taking Contrave 50.5% of patients lost at least 5% of their weight. The previous report was 56.3%. Also, the people that lost at least 10% of their weight was 28.3% not the 32.9% as previously reported. It is now expected that as a result of an "annoying clerical error" it will delay the FDA review by a few weeks.
June 1st, 2010
Today Orexigen Therapeutics announced that the FDA has accepted the NDA (new drug application) for Contrave. This means that it has been permitted to be given a FDA review. This does not mean at this time that it has been accepted for the public for the treatment of obesity.
June 17th, 2010
Today Orexigen Therapeutics was informed that the FDA will review Contrave, their treatment for obesity, on January 31st, 2011.
June 23rd, 2010
Orexigen Therapeutics released news that there has been a tentative date set for an FDA Advisory Committee Review for Contrave. This day will be December 7th, 2010.
June 25th, 2010
Contrave was reported to help diabetes patients lose weight as well as control their glucose levels according to a study lasting for 56 weeks. According to this study, 69% of the patients taking Contrave where able to achieve desirable blood glucose levels compared to the placebo group.
June 26th, 2010
Orexigen indicated with news that Contrave not only has shown it reduces weight but also depression for those suffering from obesity. In a 24 week test Contrave showed it significantly improved depressive symptoms in overweight patients with major depression.
"Treatment with Contrave32 (32mg naltrexone sustained release (SR)/360mg bupropion SR) resulted in the MADRS (Montgomery-Asberg Depression Rating Scale) score decreasing from an average of 23.7 at baseline (consistent with moderate depression) to 10.5 (mild depression) (p<0.001) at week 12 and further decreasing to 8.4 (remission) at week 24 (p<0.001). Patients who completed the study lost an average of 9.2% of total body weight and reported substantial reductions in hunger, strength and frequency of food cravings and demonstrated improved control of eating."
Studies have shown that depression tends to be higher in obese people as well as depression can often lead to increases in obesity.
July 29th, 2010
Results from the phase 3 test Cor-I trials (largest of the phase 3 and lasting 56 weeks) were made known today. They show that patients taking the diet drug Contrave where 2-3 times more likely to lose at least 5 to10% of their weight compared to those taking the placebo. More specifically to these results showed a decreased waist circumference, lower HDL cholesterol, other cardiometabolic risk factors and a decreased appetite.
The studies also showed that 34% of patients completing this study lost at least 10% of their weight compared to only an 11% of the placebo group.
What was concerning is that only about half of the people who started the trials actually stayed with it to completion and about 30% experienced various forms of nausea.
Sept 2nd, 2010
Orexigen Therapeutics has sold the marketing rights for its experimental obesity medication Contrave to Takeda Pharmaceutical Co Ltd of Japan. The deal involves a $50 million dollar upfront payment. This
gives Takeda the writes to market Contrave in United States, Mexico and Canada. But Orexigen will be able to co-promote it within the US. This agreement also states that Takeda will pay royalties starting at
20% and increasing to 35% on net sales of its drug in these countries as well as future development costs will be shared. It is estimated that if Contrave is approved, this deal could be worth up to $1 Billion.
December 3rd, 2010
In a press release today, The FDA said that Contrave caused an elevated blood pressure (hypertension) in some of the patients, but more so in ones that had type 2 diabetes. Contrave was also effective in one of the standards for being considered an effective weight loss drug having had "produced statistically significant weight loss in obese subjects" . The FDA also mentioned that Contrave "attenuates or eliminates the blood pressure and pulse reductions that are normally seen with weight loss," thus leaving a question mark on the long term risk on cardiovascular issues. The question then remains if the FDA will require more testing before a possible approval or if they potentially would require it post approval. Tuesday December 7th is the expected date the FDA panel advisory members will vote on the recommendation or disapproval of Contrave for the ultimate decision January 31st 2011.
December 7th, 2010
Today the FDA panel members voted 13-7 to recommend the approval of Contrave as a medication to fight obesity. As a result the FDA will most likely approve Contrave January 31st 2011. The FDA most often takes the advice of its panel with regards to approving medication. It is our speculation that it would be available anywhere from 6 weeks to a few months after this date.
February 1st, 2011
The Food and Drug Administration has decided that Contrave will need to undergo further study to ensure it does not significantly increase the risk of heart attacks. As a result Contrave has been rejected. It was somewhat of a surprise given that the FDA panel in December recommended its approval.
April 4th, 2011
Information about a late stage trial with Contrave showed that it did not change blood pressure on its patients. Regular blood pressure patterns where normal and had no affect from Contrave during the one year of patients taking this medication.
June 3rd, 2011
Orexigen Therapeutics today has announced that it is open to possible opportunities for its anti-obesity drug Contrave outside of the US after what it feels are unrealistic demands by the FDA for further cardiovascular risk studies. Studies that could take several years and several thousand people in addition to their already phase three trials. As a result, they have put further development of Contrave on hold. Orexigen however, has decided to appeal the decision by the FDA as it feels their demands are unreasonable. According to Orexigen, the FDA intends on holding an advisory committee on cardiovascular risks for obesity medications at the beginning of 2012. This could have a possible positive impact on Contrave in the future.
Contrave® is the brand name given to the trial obesity medication from Orexigen Therapeutics Inc . It is currently being tested to fight obesity.
Chemical Make Up