LONDON--(BUSINESS WIRE)--Aug 2, 2018--Otsuka Pharmaceutical Europe Ltd. (OPEL) today announced that the European Commission has approved an extension of indication for JINARC ® (tolvaptan) to include adult patients with CKD stage 4 Autosomal Dominant Polycystic Kidney Disease (ADPKD). 1 JINARC ® was approved in 2015 for the treatment of ADPKD in adults with CKD stage 1-3 at initiation of treatment and evidence of rapidly progressing disease. 1 The decision to include stage 4 within the JINARC ® licence comes following the submission of additional data from the REPRISE study that supported the safety and efficacy of this treatment in patients with more advanced renal disease.

Data from the tolvaptan clinical trial programme were submitted to the European Commission, including the REPRISE 2 study, which supported the efficacy and tolerability of JINARC ® observed in the previous TEMPO 3:4 3 and TEMPO 4:4 4 studies. These studies confirmed that tolvaptan slows the progression of ADPKD in patients with earlier (CKD stage 1-3) as well as those with advanced (CKD stage 4) stages of disease. 2,3,4

JINARC ® is a selective vasopressin-2-receptor antagonist containing the active substance tolvaptan. It blocks receptors in the kidneys that are responsible for the action of vasopressin. Suppression of vasopressin activity reduces the formation and enlargement of cysts and protects kidney function in patients with polycystic kidney disease (PKD). ADPKD is a progressive genetic disorder affecting the kidneys, in which fluid-filled cysts develop in the kidneys over time, enlarging these organs and reducing their ability to function normally, leading to kidney failure in most patients. 5 ADPKD is the most common type of PKD, and is the fourth leading cause of kidney failure. 5,6 Approximately 70% of European patients with ADPKD progress to end-stage renal disease (ESRD) at a median age of 58 years. 7

JINARC ® is the only pharmacological treatment indicated to slow the progression of cyst development and renal insufficiency in ADPKD patients with evidence of rapidly progressing disease.

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▼ This medicinal product is subject to additional patient monitoring. This will allow quick identification of new safety information. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to their relevant local bodies.

Notes to Editors

About the JINARC®studies

The REPRISE study was a phase 3b, multi-centre, randomised-withdrawal, placebo-controlled, double blind trial involving 1,370 subjects, comparing the efficacy and safety of tolvaptan (45 to 120 mg/day, split-dose) in ADPKD patients with CKD between late stage 2 to early stage 4 (eGFR between 25 and 65 mL/min/1.73 m 2 ). Results showed that tolvaptan significantly reduced the rate of estimated Glomerular Filtration Rate (eGFR) decline by 35% compared to placebo over 1 year (N=1,370; difference in eGFR change: is 1.27 mL/min/1.73 m 2, 95% CI 0.86-1.68, P<0.001). 2,8

TEMPO 3:4 was a phase 3, multi-centre, double-blind, randomised, placebo-controlled, parallel-arm 36-month trial involving 1,445 patients to determine long-term safety and efficacy of oral tolvaptan tablet regimens in adults with ADPKD. Results showed that tolvaptan slowed Total Kidney Volume (TKV) growth and eGFR decline, relative to placebo. 3

TEMPO 4:4 was a two-year multi-centre, open-label extension study of TEMPO 3:4, including 871 subjects, designed to provide an additional 2 years data on the long-term efficacy and safety of tolvaptan in ADPKD. Although TEMPO 4:4 did not meet its primary TKV endpoint, results were suggestive of a disease-modifying effect on the secondary endpoint of renal function (eGFR). 4

The results of the REPRISE study suggest that although the overall risks versus benefits will need to be carefully considered before initiating treatments in patients with late-stage ADPKD, in selected patients with CKD stage 4, JINARC ® has a positive benefit/risk balance. 9,10

Treatment must be initiated and monitored under the supervision of physicians with expertise in managing ADPKD.

About Otsuka

Otsuka Pharmaceutical Co., Ltd. is a global healthcare company with the corporate philosophy: “Otsuka-people creating new products for better health worldwide.” Otsuka researches, develops, manufactures and markets innovative products, with a focus on pharmaceutical products to meet unmet medical needs and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leader in the challenging area of mental health and also has R&D programs on several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

Otsuka established a presence in Europe in 1974 and today Otsuka Pharmaceutical Europe Ltd. employs approximately 600 people who channel their passion and energy into converting the latest science into much-needed medicines.

Otsuka Pharmaceutical Company is a subsidiary of Otsuka Holdings Co., Ltd. headquartered in Tokyo, Japan. The Otsuka group of companies employed 46,000 people worldwide and had consolidated sales of approximately EUR 9.8 billion in 2017.

All Otsuka stories start by taking the road less travelled. Learn more about Otsuka Pharmaceutical Company on its global website at https://www.otsuka.co.jp/en. Learn more about Otsuka in Europe at www.otsuka-europe.com or visit our Twitter page www.twitter.com/otsukaeurope.

1 European Commission. Commission implementing decision of 26.7.2018 amending the marketing authorization granted by Decision C(2015)3676(final) for “Jinarc – tolvaptan”, a medicinal product for human use. 2018.

2 Torres V et al. Tolvaptan in later-stage autosomal dominant polycystic kidney disease. N Engl J Med 2017; 377(20): 1930-42.

3 Torres V et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012; 367(25): 2407-18.

4 Torres V et al. Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial. Nephrol Dial Transplant. 2017; 32(7): 1262.

5 National Kidney Foundation (2017) Polycystic Kidney Disease. Available at: https://www.kidney.org/atoz/content/polycystic [Last accessed: July 2018]

6 Chebib F et al. Autosomal Dominant Polycystic Kidney Disease: Core Curriculum 2016. Am J Kidney Dis. May 2016; 67(5): 792-810.

7 Spithoven EM et al. Analysis of data from the ERA-EDTA Registry indicates that conventional treatments for chronic kidney disease do not reduce the need for renal replacement therapy in autosomal dominant polycystic kidney disease. Kidney Int 2014; 86: 1244-52.

8 OPDC Data on file 2017

9 European Medicines Agency. CHMP extension of indication variation assessment report. 2018.

10 European Medicines Agency. Extension of indication variation. Final clinical assessment report. 2018.

OPEL/0718/COMS/1054

OPUK/0718/JIN/1416

July 2018

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CONTACT: Otsuka

(In Europe)

Alison Ross

Head of Communications – Europe

Otsuka Pharmaceutical Europe Ltd.

+44 (0)203 7475000

ARoss@Otsuka-Europe.com

or

(Outside Europe)

Jeffrey Gilbert

Leader, Pharmaceutical Public Relations

Otsuka Pharmaceutical Co., Ltd.

+81 3 6361 7379

Gilbert.jeffrey@otsuka.jp

KEYWORD: UNITED KINGDOM EUROPE

INDUSTRY KEYWORD: HEALTH BIOTECHNOLOGY PHARMACEUTICAL

SOURCE: Otsuka Pharmaceutical Europe Ltd

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PUB: 08/02/2018 06:40 AM/DISC: 08/02/2018 06:40 AM

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