As biotech CEOs know all to well, what pharma taketh, pharma can giveth back. And that's especially true when the product in question isn't living up to its potential.

Last week, Orexigen Therapeutics Inc. was the latest recipient of a returned asset, agreeing to pay its soon-to-be-former partner Takeda Pharmaceutical Co. Ltd. $60 million plus milestones to reacquire the U.S. rights to Contrave (naltrexone HCl / bupropion HCl extended release).

Orexigen and Takeda, of Osaka, Japan, have had a tumultuous relationship after Orexigen disclosed the interim results of their cardiovascular outcomes study to too many people and the FDA decided that the companies would have to run a new clinical trial to determine whether Contrave was helping or hurting patients' hearts.

Last August, the companies amended their agreement so that Orexigen would foot the bill for the new trial up to $210 million, after which the cost would be split equally. The previous arrangement had the companies splitting the cost evenly from the start. (See BioWorld Today, Aug. 7, 2015.)

Like its competitors, Contrave never lived up to its potential. Sales of the obesity drug in 2015 came in at just $53 million.

Orexigen isn't the only one back in charge of the fate of its drugs. Sanofi SA handed back two drugs recently. Earlier this year, Mannkind Corp. and Ionis Pharmaceuticals Inc. announced that Paris-based Sanofi had returned rights to Afrezza (insulin human) and Kynamro (mipomersen sodium), respectively.

Like Contrave, neither of the drugs have produced much in the way of sales. Afrezza sales in the fourth quarter amounted to a paltry €2 million (about US$2.3 million) and Kynamro sales have been so low since the FDA approval in early 2013 that Sanofi has never disclosed how much Kynamaro has sold.

NOW WHAT?

The three companies are taking different approaches for how to handle their newly reacquired rights.

Orexigen plans to launch Contrave on its own after the 180-day transfer period or potentially sooner. The company plans to spend $80 million to $100 million per year, including about $25 million in direct-to-consumer advertising, to market Contrave. The company plans to use 160 sales reps to target about 18,000 physicians that are in the top 60 percent of obesity prescription writers.

San Diego-based Orexigen will issue $165 million of convertible senior secured notes to help fund the launch with a goal of being profitable in 2019. In addition to selling more drug than Takeda did, Orexigen's plan to become profitable includes the obesity market increasing by 5 percent to 10 percent per year and an increase in the gross-to-net ratio to 40 percent to 45 percent by 2018.

RBC Capital Markets analyst Simos Simeonidis isn't convinced Orexigen's sales force plans will be enough. "We view it as highly unlikely that Orexigen's sales force of 160 will manage to achieve what Takeda's sales force of 900 was not able to do, despite having established physician and managed care relationships," Simeonidis wrote in a note to clients.

While Orexigen plans to market Contrave on its own stateside, in Central and Eastern Europe, the company has enlisted the help of Valeant Pharmaceuticals International Inc. to commercialize the drug, which goes by the name Mysimba in the EU. The agreement, announced last week, covers the 12 EU countries – Greece, Slovenia, Slovakia, Czech Republic, Hungary, Croatia, Lithuania, Estonia, Poland, Latvia, Bulgaria, and Romania – where Mysimba is approved and also covers several non-EU countries where Valeant will apply for marketing authorization.

Mannkind, of Valencia, Calif., is taking a similar tactic to Orexigen's U.S. strategy, planning to market the drug on its own after regaining rights next month. While the company can do some planning now, the flurry of work won't begin until the reins are handed over on April 5. On its earnings call last week, Mannkind's CEO Matthew Pfeffer, pointed out that the company can't even submit its proposed new packaging with Mannkind's name on it to the FDA until the new drug application is under its control.

Management was light on the details of its plan, but Pfeffer tried to assure investors that it could succeed where Sanofi had failed. "So we've done a lot of research on the issues that prevented the product from selling more and where the mistakes were made. And so we have a preliminary plan," Pfeffer said on the conference call.

Part of that plan includes hiring a chief commercial officer, Michael Castagna, last week to lead the relaunch. Castagna tried to spin the return of Afrezza in the best possible light. "As a small pharma, Mannkind can approach their sales and marketing efforts of Afrezza with laser focus, unencumbered by internal conflicting product demand or other challenges that often exist in large pharmas."

Jefferies analyst, David Steinberg, who covers Amphastar, which provides Mannkind with its insulin API, isn't as confident in Mannkind's abilities. Steinberg removed revenue from Mannkind from his estimates of Amphastar's revenue and earnings. "Given Sanofi's recent decision to return Afrezza rights to Mannkind, there is increased risk that Mannkind could file for bankruptcy protection in the coming year if the company is unable to commercialize the drug," Steinberg wrote in a note to clients in January.

San Diego-based Ionis, on the other hand, is looking for a new partner for Kynamro, which is still being sold by Sanofi's Genzyme division for the time being.

"We are early in the process so it probably would be premature for me to go into a lot of detail. Suffice to say that we have found that there has been quite a great deal of interest with regards to new partners in taking on commercializing Kynamro," Ionis' chief financial officer, Elizabeth Hougen, told investors on an earnings call last month.

"We will have updates for you in the next few months for sure," added Stan Crooke, Ionis' CEO.

The company's 10-K filed with the SEC was a bit more cautious, "We do not intend to commercialize Kynamro ourselves. If we cannot find a suitable partner for Kynamro, we will not receive any revenue for Kynamro."