The yen also continued to firm against the dollar, rising 114.81 from 114.80 and rose 165.25 from 165.27 against the euro.

Takeda Pharmaceutical Company led the decliners in the Nikkei 225 index with a loss of 12.41% followed by losses in Marui Group of 7.93%, in Toagosei of 7%, in Terumo Corp of 6%, and in Shionogi &Company of 4.5%.

The U.S. Food and Drug Administration requested more clinical data on the cholesterol drug TAK-475. Takeda also advised doctors in the study in U.S, Europe and Japan to suspend tests using 100-milligram doses on concerns it might increase the enzyme transaminase in some patients and cause liver damage according to local newspapers in Osaka, where the company is headquartered.

Extra tests might further delay the approval of the drug and deny the company the opportunity to enter the $28 billion market. Brokerages Shimura and Mitsubishi UFJ Securities also cut the recommendation of the stock.

Takeda is under pressure to find the next mega drug to replace ACTOS, diabetes treatment drug. ACTOS, since its introduction in August 1999, has been prescribed to 70 million times to more than 8 million patients with type 2 diabetes. ACTOS patent is expiring in four years and is expected to face a still competition from generic drug makers.

Eisai Company Limited slumped 3.12% after it reported that it will delay its application for breast cancer drug with the U.S. FDA and a set-back in tests on successor drug to Aricept for the treatment of Alzheimer and experimental drug for the treatment of Parkinson disease.