Otsuka Pharmaceutical Co., Ltd.

April 12, 2013

Otsuka’s New Drug Application For Tolvaptan, An Investigational Compound For Autosomal Dominant Polycystic Kidney Disease (ADPKD), Accepted For Review By The US Food And Drug Administration (FDA)

• Tolvaptan was discovered by Otsuka in Japan and is being investigated for ADPKD. If approved by FDA, tolvaptan will become the first pharmaceutical therapy for patients with ADPKD.
• ADPKD is the most common type of inherited kidney disease.
• Otsuka’s development of tolvaptan as a treatment for ADPKD illustrates the company’s commitment to address significant unmet medical needs for diseases that have not traditionally been a priority for the pharmaceutical industry.

TOKYO, JAPAN -- April 12, 2013 -- Otsuka Pharmaceutical Co., Ltd. (Otsuka) announced today that the U.S. Food and Drug Administration (FDA) has accepted for priority review the company’s new drug application (NDA) for the potential use of tolvaptan for the treatment of autosomal dominant polycystic kidney disease (ADPKD). Phase III clinical trial results that form the basis of the regulatory filing were published in the New England Journal of Medicine.ⁱ

ADPKD is a hereditary disease characterized by the development of multiple cysts in the kidneys. ADPKD is the most common inherited kidney disease and the fourth most common overall cause of kidney failure worldwide, with the diagnosed prevalence estimated to be between 1:1,000 and 1:4,000 globally.ⁱⁱⁱ

Tolvaptan is a selective V₂ vasopressin receptor antagonist that has been hypothesized to slow the progression of ADPKD by reducing the development and growth of kidney cysts, which are characteristic of the disease. ADPKD is often associated with pain, hypertension, decreased kidney function and ultimately, kidney failure.

Under the Prescription Drug User Fee Act – or PDUFA – the FDA’s goal for reviewing a drug with Priority Review status is six months from the NDA submission date. The FDA target action date (PDUFA date) for this NDA is September 2013.

“The submission of this NDA represents an important milestone for Otsuka and for patients with this rare and devastating disease, and is another example of Otsuka’s commitment to innovation and serving unmet medical needs” said Dr. Taro Iwamoto, President and Representative Director, Otsuka Pharmaceutical Co., Ltd. “Tolvaptan was discovered by Otsuka in Japan, and, if approved by the FDA, will become the first approved pharmaceutical therapy for patients who suffer from ADPKD.”

About ADPKD

Autosomal Dominant (ADPKD) is characterized by the development of multiple, non-malignant cysts arising in the kidneys due to inherited or acquired genetic mutation(s).^ii,iii Cyst development and growth in both kidneys causes slow deterioration of kidney function, and in approximately 50% of patients with ADPKD, leads to end-stage renal disease (ESRD).^iv

ADPKD typically results in symptom manifestations (e.g. hypertension and kidney pain) in adulthood.ⁱⁱⁱ

• *i：Article published on November 3rd, 2012 at NEJM.org
• *ii：Torres, VE, Harris, PC, and Pirson, Y. Autosomal Dominant Polycystic Kidney Disease Lancet. 2007;369:1287-1301.
• *iii：Tan Y, Blumenfeld J, and Rennert H. Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs. Biochimica Biophysica Acta. 2011;1812:1202-1212.
• *iv：Patel V, Chowhury R, and Igarashi P. Advances in the pathogenesis and treatment of polycystic kidney disease. Curr Opin Nephrol Hypertens. 2009;18:99-106.