MOVICOL® Launched in Japan-The First Polyethylene Glycol Preparation for Chronic Constipation in JapanThis material is an English translation of the press release issued on November 29, 2018 inJapanese, and the Japanese release is given priority regarding content and interpretation.
November 29, 2018
Mochida Pharmaceutical Co., Ltd.
EA Pharma Co., Ltd.
Eisai Co., Ltd.
Mochida Pharmaceutical Co., Ltd. (President, Naoyuki Mochida; Headquarters, Shinjuku-ku,Tokyo, Japan, “Mochida”), EA Pharma Co., Ltd. (President, Yuji Matsue; Headquarters,Chuo-ku, Tokyo, Japan, “EA Pharma”) and EA Pharma’s parent company Eisai Co., Ltd.
(CEO, Haruo Naito; Headquarters, Bunkyo-ku, Tokyo, Japan, "Eisai") announced today thatthe constipation treatment “MOVICOL®” (Development code AJG555) was included inJapan’s National Health Insurance drug price list as of November 20, 2018, and Mochida andEA Pharma launched the product onto the Japan market today.
MOVICOL® is the first polyethylene glycol preparation indicated for treatment of chronic
constipation1) in Japan, available for adults and children 2 years of age and older.MOVICOL®
increases the moisture in the intestinal tract by osmolality of its main ingredient polyethylene
glycol (macrogol 4000), which increases fecal moisture, softens feces, increases fecal volume
and physiologically activates the peristaltic movement of the colon to promote bowel
movement. Furthermore, MOVICOL® is a powdered medicine to be dissolved in water before
administration, which enables suitable increase or decrease of the dose to obtain the preferredstool consistency.

Outside Japan, this product has been marketed mainly in Europe by Norgine B.V.
(Headquarters, the Netherlands, “Norgine”) under the brand name MOVICOL* and is used bymany patients with chronic constipation. In Japan, the Evaluation Committee on Unapprovedor Off-Labeled Drugs with High Medical Needs2) of Ministry of Health, Labour and Welfare
recognized the “high unmet medical needs” of polyethylene glycol preparations for chronic
constipation, and Ajinomoto Pharmaceuticals Co., Ltd. (now EA Pharma) developed thisproduct with Mochida for oral chronic constipation treatment in pediatric and adult patients inJapan under the license granted by Norgine to Ajinomoto Pharmaceuticals Co., Ltd. (now EAPharma).
In a placebo-controlled double-blind PIII clinical trial in adults conducted in Japan, theMOVICOL® group demonstrated a statistically significant increase in spontaneous bowel
movement frequency3) (the primary endpoint) compared to the placebo group. In thesubsequent 52-week consecutive administration period, the spontaneous bowel movement
frequency was steadily maintained in most cases. In a PIII clinical trial (a baseline-controlledopen-label study) in pediatric patients, a statistically significant increase in spontaneous
bowel movement frequency (the primary endpoint) was observed compared to baseline. The
major adverse drug reactions in these trials were diarrhea and abdominal pain.
Mochida and EA Pharma have commenced distribution of the product under the same brandname in Japan. EA Pharma and Eisai jointly provide information for the proper use ofMOVICOL® under a co-promotion agreement.
The prevalence of constipation is high in young women and both elderly men and women,
and the symptoms can become severe particularly in pediatric patients. The symptoms ofconstipation include reduced bowel movement, feeling of incomplete evacuation, and hardstools. When the symptoms become chronic, many patients suffer from a decline of QOL(Quality of Life). With the new treatment MOVICOL® in addition to “GOOFICE® 5 mg Tablet”(bile acid transporter inhibitor for chronic constipation treatment) launched in Japan in April
2018, Mochida, EA Pharma and Eisai are striving to increase treatment options for patientswith chronic constipation and diverse disease histories as they seek to further contribute toaddressing the needs of, and increasing the benefits provided to, patients, their families andhealthcare providers.
1) Excluding structural disease-induced constipation
2) The Evaluation Committee on Unapproved or Off-Labeled Drugs with High Medical Needs
This committee was organized in the Ministry of Health, Labour and Welfare to evaluate the medical needs of the drugsand indications that are not approved in Japan (“unapproved or off-labeled drugs”) and the appropriateness of filing thepublic knowledge-based application and requirement of additional studies for filing the marketing and manufacturing
application to promote development of unapproved or off-labeled drugs by pharmaceutical companies.
3) Defecation without use of laxative, enema or manual disimpaction

EndMore Information
1. “MOVICOL®” Product Outline
Brand name
Ingredients

Formulation,contents

Indication

MOVICOL®
macrogol 4000, sodium chloride, sodium bicarbonate,
potassium chloride
Powdered preparation for oral fluid
1 sachet (6.8523g) includes the following ingredients:
Macrogol 4000
6.5625g
Sodium chloride
0.1754g
Sodium bicarbonate
0.0893g
Potassium chloride
0.0251g
Chronic constipation (excluding structural disease-inducedconstipation)
Dissolve this powdered medicine in water and administer orally.
For children aged between 2 and 6 years, normally 1 sachet should
be administered orally at once per day for the initial dose. Then, thedose can be increased or decreased depending on symptoms,administered orally 1-3 times per day. The maximum daily dose is 4sachets (up to 2 sachets at once). An interval of at least 2 days isneeded between every dose escalation, and the dose should not
be increased in excess of 1 sachet per day.

Dosage andadministration

For children aged between 7 and 11 years, normally 2 sachetsshould be administered orally at once per day for the initial dose.
Then, the dose can be increased or decreased depending on
symptoms, administered orally 1-3 times per day. The maximum
daily dose is 4 sachets (up to 2 sachets at once). An interval of atleast 2 days is needed between every dose escalation, and thedose should not be increased in excess of 1 sachet per day.
For adults and children aged 12 years and older, normally 2sachets should be administered orally at once per day for the initialdose. Then, the dose can be increased or decreased depending on
symptoms, administered orally 1-3 times per day. The maximum
daily dose is 6 sachets (up to 4 sachets at once). An interval of atleast 2 days is needed between every dose escalation, and thedose should not be increased in excess of 2 sachets per day.

Packaging
National Health
Insurance Drug(NHI) Price
Date of manufacture
and marketing
approval

100 sachets
MOVICOL® 6.8523g 1 sachet ¥83.90

September 21, 2018

Date of inclusion inthe NHI drug pricelist
LaunchManufacturer anddistributor
Promotion alliancewith EA Pharma Co.,Ltd.
Distributor

November 20, 2018
November 29, 2018
EA Pharma Co., Ltd.

Eisai Co., Ltd.
Mochida Pharmaceutical Co., Ltd.

2. About “GOOFICE® 5 mg Tablet”“GOOFICE® 5 mg Tablet”, which EA Pharma in-licensed from Albireo AB (Headquarters,Sweden), is an orally available chronic constipation** treatment having a novel mechanism ofaction. “GOOFICE® 5 mg Tablet” inhibits the bile acid transporter that regulates reabsorptionof bile acids thereby increasing the flow of bile acids to the colon, which is expected toenhance colonic motility. Mochida and EA Pharma have a joint development and marketing
agreement for “GOOFICE® 5 mg Tablet”, and started distribution of “GOOFICE® 5 mg Tablet”
respectively under the same brand name on April 19, 2018 in Japan. EA Pharma also has aco-promotion agreement with Eisai. EA Pharma and Eisai jointly provide information for theproper use of “GOOFICE® 5 mg Tablet”.
**Excluding structural disease-induced constipation

3. About Mochida Pharmaceutical Co., Ltd.
Mochida Pharmaceutical Co., Ltd. has been committed to research and development ofinnovative pharmaceutical products since its establishment thereby providing distinctive
medicines to the medical field. Currently, the core pharmaceutical business focusesresources on the targeted areas of cardiovascular medicine, obstetrics and gynecology,dermatology, psychiatry and gastroenterology, while also providing medicine for intractabledisease as well as generics including biosimilars, to meet medical needs.
For more information on Mochida Pharmaceutical Co., Ltd.,
please see http://www.mochida.co.jp/

4. 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 AjinomotoGroup having amino acid as its business core. EA Pharma is a gastrointestinal specialty
pharma with a full value chain covering R&D, logistics and sales & marketing.
For more information on EA Pharma Co., Ltd., please see http://www.eapharma.co.jp/

5. About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company
headquartered in Japan. We define our corporate mission as "giving first thought to patientsand their families and to increasing the benefits health care provides," which we call ourhuman health care (hhc) philosophy. With approximately 10,000 employees working acrossour global network of R&D facilities, manufacturing sites and marketing subsidiaries, westrive to realize our hhc philosophy by delivering innovative products to address unmet
medical needs, with a particular focus in our strategic areas of Oncology and Neurology.
For more information on Eisai Co., Ltd., please see https://www.eisai.co.jp/*“MOVICOL” is a registered trademark of the Norgine group.
(In this document, MOVICOL means the product marketed in non-Japan countries.)