Japanese pharmaceutical firm Takeda has reached an agreement with rival Shire for a £46 billion takeover, after several previous offers were declined earlier this month.

Under the terms of the acquisition, each Shire shareholder will receive $30.33 for each Shire share and either 0.839 new Takeda shares or 1.678 Takeda ADSs. The acquisition terms imply an equivalent value of £48.17 per Shire share.

Up to three Shire directors are set to join the board once the acquisition is completed, and the takeover will take effect from the first half of 2019.

Takeda said it hopes the deal will create a global, values-based, R&D driven biopharmaceutical leader incorporated and headquartered in Japan and strengthen its core therapeutic areas.

Shire chief executive Flemming Ornskov said: “I would like to thank the entire Shire team for all that we have accomplished over the last five years to transform Shire into the leading rare disease biotech company and a tenacious champion for patients in need.

“I am confident that this relentless focus will enable us to continue delivering against our priorities throughout this process.”

Shares in Shire (LON:SHP) are currently trading up 2.85 percent, at 3,966.00 (0831GMT).