LONDON/NEW YORK (Reuters) - London-listed drugmaker Shire Plc said on Tuesday it was willing to recommend to its shareholders a deal with Takeda Pharmaceutical Co, after the Japanese company sweetened its acquisition offer to 46 billion pounds ($64 billion).

FILE PHOTO: Vitamins made by Shire are displayed at a chemist's in northwest London, Britain, July 11, 2014. REUTERS/Suzanne Plunkett/File Photo

The development, first reported by Reuters earlier on Tuesday, represents a major breakthrough for the companies in their negotiations, following a pursuit that started on March 28 when Takeda said it was considering a bid for Shire. Since then, Takeda has made five offers, the latest earlier on Tuesday.

Shire said in a statement it had agreed to extend a Wednesday regulatory deadline for the deal talks to conclude to May 8 in order to allow Takeda to carry out more due diligence and firm up its bid. Shire added that the deadline could be extended further, if needed.

Any deal between the two companies is still subject to the resolution of several issues, including completion of due diligence by Shire on Takeda, Shire said.

Takeda added in its own statement that it intended to maintain its dividend policy and investment-grade credit rating following the deal.

Shire focuses on treatments for rare diseases and attention deficit hyperactivity disorder. The acquisition would be the largest ever overseas acquisition by a Japanese company and propel Takeda, led by Frenchman Christophe Weber, into the top ranks of global drugmakers.

It would significantly boost Takeda’s position in gastrointestinal disorders, neuroscience, and rare diseases, including a blockbuster hemophilia franchise.

But the transaction would be a huge financial stretch, since Shire is worth considerably more than the Japanese group. Ambitious cost cutting will be required to make the deal

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