Shares of Takeda Pharmaceutical Co. fell the most in nine years after the firm disclosed it is considering a bid for Shire PLC that could approach $50 billion (about ¥5.3 trillion), which would be the Japanese company’s biggest takeover ever.

The decline in early Tokyo trading shaved $3 billion from Takeda's market cap. Coupled with a rally in Shire's stock on the news, the valuation gap between the two companies widened by almost $6.5 billion, posing a bigger financial challenge for Takeda if it decides to go forward with an offer.

"Takeda is just desperate to beef up its pipeline, and they've been doing small bits of acquisitions on the biotech side," said Fumiyoshi Sakai, a Tokyo-based analyst at Credit Suisse Securities. "But how they are going to finance $40-some billion? That's another one."