In the largest-ever takeover by a Japanese company, drugmaker Takeda has clinched a deal to acquire Shire for $62 billion, ending its lengthy courtship of its Irish rival and giving it a lucrative portfolio of rare disease drugs.

Shire had rejected four previous offers from Takeda due to concerns not only about the price but also the high ratio of stock to cash. But the companies announced Tuesday they had reached agreement on a recommended offer that will pay Shire shareholders $66.56 per share — $30.33 in cash, with the remainder in the form of 0.839 of a new Takeda share.

The deal would be the world’s biggest takeover so far this year and represents a 59.6% premium to Shire’s closing price on March 27, before Takeda first declared its interest.

“Shire’s highly complementary product portfolio and pipeline, as well as experienced employees, will accelerate our transformation for a stronger Takeda,” Christophe Weber, the Japanese firm’s CEO, said in a news release.

Shire makes such profitable drugs as the ADHD treatments Adderall and Vyvanse. Its rare disease drugs have high profit margins and it also offers blood-derived therapies for serious conditions such as hemophilia.

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Takeda’s best-selling drugs treat metabolic diseases, cancer, and cardiovascular problems. Since becoming Takeda’s CEO in 2015, Reuters reports, Weber “has been hunting for acquisitions to make the company more global and reduce its exposure to a mature Japanese pharmaceutical market.”

While Shire’s board has accepted Takeda’s offer, it still requires the approval of 75% of Shire shareholders and two-thirds of Takeda investors. Takeda will need to take on debt equal to five times EBITDA to complete the acquisition, prompting Standard & Poor’s to warn of a potential credit downgrade.

“Buying Shire is a big financial stretch for Takeda but Weber believes it will generate substantial cash flow, enabling the enlarged group to pay down its borrowings quickly,” Reuters said.

Shire has grown rapidly through acquisitions to generate revenues of about $15.2 billion last year but it has been facing increased competition from generic drugs. It has annual operating profits of $6 billion compared to Takeda’s $2 billion.

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