-There are none for ages and then several come along at once. In the United States, physicians managing obese patients were essentially only able to prescribe Roche's Xenical (orlistat) and phentermine (and other noradrenergic anorectic agents) for years, and then Arena Pharmaceutical/Eisai's Belviq (lorcaserin) and Vivus's Qsymia (phentermine/topiramate fixed-dose combination [FDC]) were approved in June and July, respectively, during 2012. Then since September 2014, we have seen the approval of Orexigen Therapeutics/Takeda Pharmaceutical's Contrave/Mysimba (naltrexone/bupropion FDC) and Novo Nordisk's Saxenda (liraglutide 3 mg) in the United States and Europe.
The European approvals are of particular note, owing to the limited number of prescription treatment options available, which is basically one: orlistat. The withdrawal of several antiobesity products owing to serious safety concerns has led to particularly tough regulatory scrutiny of novel weight loss agents. European marketing authorization for Qsymia and Belviq has been sought but neither has been granted approval. Even though European thought leaders recognize the important unmet need in their region they tend to be more cautious about the potential for weight loss drugs than their U.S counterparts.
Contrave, which is to be marketed as Mysimba in Europe, has seen stronger uptake in the United States than was achieved by Belviq and Qsymia. This is probably due to physicians perceiving Contrave to have a better risk-benefit profile than its competitors: Qsymia is highly efficacious but has potentially serious safety concerns, whereas Belviq has less safety concerns but only modest efficacy. Xenical's peripheral action makes it the safest option, according to thought leaders, but it has only modest efficacy and it is poorly tolerated owing to the need for three tablets per day and additional fat soluble vitamins, as well as some rather unpleasant gastrointestinal side effects. Moreover, the price of the recent generic orlistat products does not seem to be much less than Xenical. Saxenda, too, appears to offer a happy medium with respect to efficacy, safety, and tolerability. However, it is an injection, which will put some patients off and encourage some physicians to use it after exhausting oral therapies; it is also likely to be an expensive option.
So what does it mean for physicians and patients. More treatment between diet and exercise and bariatric surgery can only be a good thing. In the United States, the new approvals offer more treatment options, but in Europe they will triple the treatment options and transform the market. Although uptake is expected to be relatively slow, Contrave will eat into Xenical patient share and pick up good sales as a result. Saxenda is likely to be used less, probably in later lines of therapy and in severely obese and prediabetic patients, but its anticipated higher price should also result in solid sales. However, reimbursement will be challenging for these agents in both regions. Nonetheless, I am sure there are a number of patients and doctors who are keen to catch the Contrave/Mysimba and Saxenda buses as they arrive.
Tim Blackstock, M.B. Ch.B., M.Phil., is a Senior Analyst in the Cardiovascular, Metabolic, and Renal Disorders team at Decision Resources Group.
In-depth analysis of obesity, with accompanying epidemiology driven sales forecast models, are presented in Decision Resources Group's Obesity Pharmacor, available here.