For the second time this summer, a Japanese drugmaker has agreed to pay $50 million upfront for the rights to a forthcoming diet pill. This time, Takeda Pharmaceuticals is giving Orexigen Therapeutics $50 million for exclusive North American marketing rights (but co-promotion in the US) for Contrave and another $1 billion for meeting regulatory and sales milestones, along with double-digit royalties (see statement).

Just a few weeks ago, Eisai paid $50 million for the rights to sell Arena Pharmaceuticals’ lorcaserin in the US; another $160 million based on development and approval milestones, and a $1.16 billion, one-time payment that may follow based on annual sales. Neither pill has been approved - an FDA advisory panel will review Arena’s lorcaserin on Sept. 16, while Orexigen’s Contrave is reviewed in December.

The moves underscore how Japanese drugmakers - which, as a group, have been more aggressive in buying other drugmakers in the recent past - are desperate to widen their reach in the US and, in the process, lay claim to a diet pill market that has been underserved thanks to a series of spectacular failures over safety concerns that sparked recalls and rejections. Think fen-phen or Acomplia.

Whether they are making the right bet is uncertain. In July, an FDA advisory committee rejected Vivus Pharmaceuticals’ Qnexa pill over doubts about usage by pregnant women and psychiatric side effects. Orexigen’s Contrave is similar to Qnexa - both are two-drug combos, although Contrave combines the Wellbutrin antidepressant and ReVia, which is used to fight opioid and alcohol addiction.

The real issue for Takeda, though, is that Contrave can cause a temporary increase in blood pressure (look here). Given concerns over cardiovascular risks - see the latest worries about Meridia - one can imagine an FDA panel viewing yet another diet pill with heightened scrutiny. Despite the fact that truly effective diet drugs are lacking, Takeda’s investment may prove to be a classic fat chance.