March 19, 2020
EA Pharma Co., Ltd.
Eisai Co., Ltd.

All-case Surveillance Condition for Approval of “Actonel® 17.5 mgtablets” for Treatment of Paget’s Disease of Bone Cleared in JapanEA Pharma Co., Ltd. (President, Yuji Matsue; Headquarters, Tokyo, Japan) and its parent company EisaiCo., Ltd. (CEO, Haruo Naito; Headquarters, Tokyo, Japan) announced that Japan’s Ministry of Health,Labour and Welfare (MHLW) has given notification of the results of reexamination to the effect that the“all-case surveillance” specified drug use-results survey condition required for the approval of “Actonel®
17.5 mg tablets” (risedronate sodium hydrate) indicated for treatment of Paget’s disease of bone has beenlifted.
In July 2008, MHLW approved the indication for treatment of “Paget’s disease of bone” for Actonel 17.5
mg tablets” with the following conditions for approval: “Because of the very limited number of subjects
treated in the Japanese clinical trials, the applicant is required to conduct all-case drug use-results survey
until data from a certain number of patients are accumulated after market launch, in order to identify thebackground information of patients treated with the product and collect safety and efficacy data on theproduct in the early post-marketing period, and thereby take necessary measures to ensure proper useof the product.”
Based on the safety data in 307 patients and efficacy data in 276 patients submitted to MHLW as theresults of analyses of all-case surveillance, MHLW has concluded that the all-case surveillance wasconducted properly and the necessary measures to ensure proper use of the product were being taken
sufficiently to lift the condition.
EA Pharma Co., Ltd. and Eisai Co., Ltd. continually strive to promote proper use of the product and provide
timely additional information of the product to increase benefits to patients and their families.

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More Information■About “Actonel® 17.5 mg tablets” (risedronate sodium hydrate)“Actonel®” is a bisphosphonate originally synthesized by Norwich Eaton Pharmaceuticals, Inc.
(US) (now Allergan plc). In Japan, “Actonel” launched with indication for once-daily osteoporosis
treatment under the brand name of “Actonel 2.5 mg tablets” in May 2002. Later, additional
formulations - once-weekly “Actonel 17.5 mg tablets” in June 2007 and once-monthly “Actonel 75mg tablets” in February 2013 - became available in the market. “Actonel” has contributed
significantly to the treatment of patients suffering from osteoporosis. “Actonel 17.5 mg tablets”
were further approved for the additional indication for treatment of Paget’s disease of bone in July
2008. “Actonel” is manufactured by EA Pharma Co., Ltd. as the marketing authorization holder,and is marketed by Eisai Co., Ltd in Japan.
■About Paget’s disease of bone
Paget's disease of bone is a metabolic disorder of the bone. Its etiology is unknown. Paget's
disease of bone causes deformity and thickening of the bone due to locally abnormally
accelerated bone resorption and subsequent formation. The major symptoms are pain and bone
deformation of the affected area. Paget’s disease of bone can sometimes complicate
osteoarthritis and neurologic symptoms, which can seriously deteriorate QOL of patients. Further,
Paget’s disease of bone is known to develop to secondary malignant neoplasms including
osteosarcoma, and a highly effective treatment is desired. The prevalence of this disease is very
low in Japan: 2.8 people out of a population of 1 million, according to a report1).
1)

Hashimoto J et al., Prevalence and clinical features of Paget’s disease of bone in Japan. Osteoporosis Japan. 2007; 15(2):241-245■About the results of specified (all-case) drug use-result survey
The specified drug use-result survey is conducted for the purpose of collecting and confirmingside effect incidence by symptom, quality, efficacy and safety information in pediatric, geriatric,pregnant patients, patients with renal dysfunction, hepatic dysfunction, patients who use the drug
for a long time or those patients with any limitations or conditions in drug use. The manufacturing
and distributing company of the drug or the like undertakes the clinical survey.
The drug use-result survey specified in this release was conducted by central registration method
to investigate the safety and efficacy of “Actonel 17.5 mg tablets” and “Benet 17.5 mg tablets”* inactual drug use under the approved conditions. The patients registered were all the 315 patients
who started use of the drug for treatment of Paget’s disease of bone within the period from August
2008 through January 2016 and continued administration of the drug once daily for 8 weeks(administration period) with 48 week’s observation period in 92 medical facilities located in Japan.
In the 307 safety analytical set, side effects were observed in 15% (46 out of 307 patients). The
major side effects were gastrointestinal disorders (6.8%, 21/307 patients) such as

nausea (5cases), abdominal discomfort (4 cases), constipation and dyspepsia (3 cases, respectively),esophagitis and loose stool (2 cases, respectively); metabolism and nutritional disorders (2.3%,7/307 patients) of hypocalcemia (7 cases); general and systemic disorders and local area
symptoms (1.6%, 5/307 patients) of fever (3 cases) and malaise (2 cases); and hepatobiliary
disorders (1.3%, 4/307 patients) such as liver dysfunction (2 cases), musculoskeletal andconnective tissue disorders (1.0%, 3/307 patients) of back pain (2 cases).
With respect to efficacy, excess serum alkaline phosphatase** changes were similar to the results
obtained in the Phase III clinical trial in Japan, and improvement of pain was observed. All bonemetabolism markers (urine type I collagen cross-linked N-telopeptide, urine deoxypyridinoline andserum bone alkaline phosphatase) declined as compared with the levels at the initiation ofadministration.
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Takeda Pharmaceutical Co., Ltd. has obtained manufacturing and marketing approval for Bennet Tablets 17.5
mg (risedronate sodium hydrate).
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Excess serum alkaline phosphatase = actual measurement value of serum ALP －(maximum standard value +minimum standard value)/2■About EA Pharma Co., Ltd.
EA Pharma Co., Ltd., a subsidiary of Eisai Co., Ltd. for gastrointestinal disease area, wasestablished in April 2016 by integration of the gastrointestinal business unit with more than 60 year’s
history of the Eisai Group and the gastrointestinal business unit of the Ajinomoto Group having
amino acid as its business core. EA Pharma Co., Ltd., is a gastrointestinal specialty pharmaceuticalcompany with a full value chain covering R&D, production & logistics and sales & marketing.
For further information on EA Pharma Co., Ltd.,, please visit http://www.eapharma.co.jp/en/■About Eisai Co., Ltd.
Eisai Co., Ltd. defines our corporate mission as "giving first thought to patients and their families
and to increasing the benefits health care provides," which we call our human health care (hhc)philosophy. With approximately 10,000 employees working across our global network of R&D
facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy bydelivering innovative products to address unmet medical needs, with a particular focus in ourstrategic areas of Neurology and Oncology.
As a global pharmaceutical company, our mission extends to patients around the world throughworking with key stakeholders to improve access to medicines in developing and emerging countries.
For further information on Eisai Co., Ltd., please visit https://www.eisai.com.