Healthcare Industry News:  tolvaptan 

Biopharmaceuticals Regulatory

 News Release - March 24, 2014

Otsuka Pharmaceutical's Samsca(R) Approved in Japan as the World's First Drug Therapy for ADPKD, a Rare Kidney Disease

Samsca, discovered and developed by Otsuka Pharmaceutical Co., has been approved in Japan as the first drug treatment in the world to slow the progression of autosomal dominant polycystic kidney disease (ADPKD). With Samsca, long-term progression of the disease may be delayed, which now opens a treatment option for people in Japan with ADPKD.

ADPKD is a genetic disease in which the kidneys become enlarged due to proliferation of fluid-filled cysts. As the disease progresses renal function declines and complications ensue, including hypertension, hematuria and abdominal pain. The decline in renal function is such that by 70 years of age one half of those afflicted with ADPKD reach end-stage renal failure, with quality of life compromised and a burdensome prognosis.i The number of diagnosed patients is estimated to be 30,000 cases in Japan, 200,000 in Europe and 120,000 in the U.S.ii, iii, iv

From 2004, clinical trials were conducted with more than 1,400 patients with ADPKD in 15 countries. In phase-III trials, the rate of change in total kidney volume, a measure of disease progression in early-stage ADPKD patients, was found to be curtailed by approximately 50% when compared to placebo treatment.v Application for regulatory approval was submitted in Europe in December, 2013, while discussions are underway in consultation with the FDA in the U.S. to expeditiously determine the path forward for resubmission.

TOKYO--(Healthcare Sales & Marketing Network)--Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announced it has become the first company in the world to obtain regulatory approval for a pharmacological treatment of autosomal dominant polycystic kidney disease (ADPKD). Samsca® (generic name: tolvaptan) has been approved in Japan in 7.5-mg and 15-mg tablet forms for extended use for the additional indication of ADPKD. Also, the new dosage form of 30-mg Samsca tablets has received approval for the indication of ADPKD.

Samsca was developed over the past 26 years by the efforts of many researchers in Otsuka’s Tokushima, Japan research facility. It is currently used in 14 countries and territories around the world as an aquaretic drug, which facilitates excretion of only free water without electrolyte loss due to its antagonist action on vasopressin V2 receptors. Upon a discovery that proliferation and enlargement of renal cysts are hindered by suppression of cAMP formation at vasopressin V2 receptorsvi, Otsuka launched a new effort from 2004 to develop a drug for the rare disease ADPKD, in conjunction with world specialists including Dr. Vicente E. Torres of the Mayo Clinic in the U.S. In global clinical trials (the TEMPO 3:4 trialvii) conducted in 15 countries on more than 1,400 patients with ADPKD, Samsca was shown to significantly suppress the rate of increase in total kidney volume by approximately 50% more than a placebo. The results of these trials were published in November, 2012 in the New England Journal of Medicine.v

Taro Iwamoto, CEO of Otsuka Pharmaceutical Co., Ltd., stated, “Development of a pharmacotherapy for ADPKD, a rare disease leading to end stage renal failure, has been difficult. Lack of a fundamental therapy for this disease has over many years been a great difficulty for people with ADPKD. We are very pleased that, through this approval, we may be able to contribute something to these patients and their families. Through Samsca’s completely new mode of action, development of a new category of indications was possible. While rigorously pursuing safety and effectiveness, in the future we look forward to having something to present to patients who suffer from this disease, not only in Japan but all over the world.”

Eiji Higashihara, professor of nephrology at Kyorin University School of Medicine, noted, “Since there has been no drug treatment for ADPKD up to now, this recent approval is great news for these patients and their families, and also for those of us who treat them. On the other hand, physicians and other health care workers need to thoroughly know the indications of Samsca for treatment of ADPKD. We further need to keep in close touch with the patients and their families in paying attention to safe use of Samsca. It is important that, through teamwork, we carefully nurture this medicine that has been developed here in Japan.”

In Europe, as of December, 2013, an application for regulatory approval of tolvaptan in ADPKD had been received and is under review. In the United States, based on a review issued by the FDA, we have continued discussions with them regarding supplementary data and the path forward for resubmission.


ADPKD is a disease arising from one of two possible genetic mutations in which innumerable cysts (sacs in which fluid accumulates) form on both kidneys to such a degree that the kidneys become multiple times larger than normal, leading to gradual diminution of renal function. If either parent has ADPKD, a child has a one-in-two probability of inheriting the disease. In most cases symptoms begin to show up in the third or fourth decade of life in the form of complaints such as blood in the urine, abdominal or low back pain, and abdominal distention. Before the kidneys start to malfunction hypertension often occurs, with complications like cerebral aneurysms and hepatic cysts occurring more frequently than usual. By age 70, close to half of ADPKD patients are estimated to have end-stage renal failure, necessitating dialysis or renal transplantation. ADPKD is the fourth-leading cause of end-stage renal failure.viii The disease occurs relatively frequently among genetic disorders, with approximately 30,000 people diagnosed in Japan, 200,000 in Europe and 120,000 in the U.S.

i Ministry of Health, Welfare and Labor of Japan, Progressive Renal Diseases Research Team, Polycystic kidney disease clinical guideline, Aug. 2010

ii Higashihara E, et al. “Prevalence and renal prognosis of diagnosed autosomal dominant polycystic kidney disease in Japan. Nephron.”1998;80:421-7

iii European Medicines Agency. EU/3/13/1175. 2013. Available from:

iv Data on File. TOLV-002. Otsuka America Pharmaceuticals, Inc.

v Torres, VE et al. “tolvaptan in patients with autosomal dominant polycystic kidney disease.” The New England Journal of Medicine, 2012: 367 (25): 2407-2418

vi Gattone, VH et al. “Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist.” Nature Medicine, 2003: 9 (10): 1323-1326

vii tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Disease and its Outcomes

viii Elhassan E, et al. “Progress on autosomal dominant polycystic kidney disease.” The Arab Journal of Nephrology and Transplantation 2009; 2(2): 27-44

Source: Otsuka Pharmaceutical

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