On Monday Takeda Pharmaceutical confirmed to acquire Shire for £45.3 billion ($61.50 billion). The final deal will be 46 percent cash and 54 percent stock.

The deal will be the largest overseas acquisition by a Japanese company, led by Frenchman Christophe Weber. The tie-up inducts frantic months of mergers & acquisitions as big drug-makers like Novartis and Sanofi look to improve their conduit by bringing in promising medicines developed by younger companies.

The group will be a Japanese leader in gastroenterology, neuroscience, oncology, rare diseases and blood-derived therapies which are used for hemophilia

The deal happened on the last day for Takeda to make a firm bid.  Previously Shire rejected four offers, due to price concerns. Shire shareowners will receive $30.33 in cash and 0.839 new Takeda shares or 1.678 Takeda American depositary shares. Valuing the offer at 48.17 pounds a share based on the latest price and exchange rate.

Shire's shares, which had been trading about 10 pounds below the value of Takeda's offer, traded 4 percent higher at just over 40 pounds, still well under the agreed price and indicating that shareholders still have reservations.

Although the deal must get the support of 75 percent of Shire's voting shareholders, some of whom do not want to hold Takeda paper, Weber told reporters he believed investors would back the transaction.

"Their board and our board is confident that both shareholders will see the benefit of the acquisition," he said.