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Otsuka Receives Complete Response Letter From U.S. Food And Drug Administration For Tolvaptan For Use In Patients With Autosomal Dominant Polycystic Kidney Disease
Otsuka Pharmaceutical Submits New Drug Application in Japan for Tolvaptan for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
may 30 2013
- Tolvaptan was discovered by Otsuka in Japan, and its primary results from a global clinical trial involving 1,400 ADPKD patients from 15 countries, which demonstrated a statistically significant reduction in the rate of total kidney volume, were published in New England Journal of Medicine in 2012. It is also currently under a fast track review in the US, following our announcement of FDA accepting to review the application in April 2013.
- ADPKD is a hereditary and often physically and mentally burdensome disease characterized by the development of multiple cysts in the kidneys. ADPKD is often associated with pain, hypertension, decreased kidney function and ultimately, kidney failure that may result in hemodialysis or kidney transplantation.
- There are estimated to be approximately 31,000 ADPKD patients in Japan, and the diagnosed prevalence is estimated to be between 1:1000 and 1:4000 globally.
(Tokyo, Japan, May 30, 2013) – Otsuka Pharmaceutical Co., Ltd. Today announced it filed an application with the Pharmaceutical and Medical Devices Agency in Japan (PMDA) to market its novel compound 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 in November 2012. The MHLW has designated tolvaptan as an Orphan Drug.http://www.otsuka.co.jp/en/release/2013/0603_02.html
Tolvaptan (INN), also known as OPC-41061, is a selective, competitive vasopressin receptor 2 antagonist used to treat hyponatremia (low blood sodium levels) associated withcongestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone(SIADH). Tolvaptan was approved by the U.S. Food and Drug Administration (FDA) on May 19, 2009, and is sold by Otsuka Pharmaceutical Co. under the trade name Samsca and in India is manufactured & sold by MSN laboratories Ltd. under the trade name Tolvat & Tolsama.
Tolvaptan is also in fast-track clinical trials for polycystic kidney disease. In a 2004 trial, tolvaptan, when administered with traditional diuretics, was noted to increase excretion of excess fluids and improve blood sodium levels in patients with heart failure without producing side effects such as hypotension (low blood pressure) or hypokalemia(decreased blood levels of potassium) and without having an adverse effect on kidney function. In a recently published trial (TEMPO 3:4 ClinicalTrials.gov number, NCT00428948) the study met its primary and secondary end points. Tolvaptan, when given at an average dose of 95 mg per day over a 3-year period, slowed the usual increase in kidney volume by 50% compared to placebo (2.80% per year versus 5.51% per year, respectively, p<0.001) and reduced the decline in kidney function when compared with that of placebo-treated patients by approximately 30% (reciprocal serum creatinine, -2.61 versus -3.81 (mg/mL)-1 per year, p <0.001)
- Shoaf S, Elizari M, Wang Z, et al. (2005). “Tolvaptan administration does not affect steady state amiodarone concentrations in patients with cardiac arrhythmias”. J Cardiovasc Pharmacol Ther 10 (3): 165–71. doi:10.1177/107424840501000304. PMID 16211205.
- Otsuka Maryland Research Institute, Inc.
- Gheorghiade M, Gattis W, O’Connor C, et al. (2004). “Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial”. JAMA 291 (16): 1963–71. doi:10.1001/jama.291.16.1963. PMID 15113814.
- (2012) Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
- Kondo, K.; Ogawa, H.; Yamashita, H.; Miyamoto, H.; Tanaka, M.; Nakaya, K.; Kitano, K.; Yamamura, Y.; Nakamura, S.; Onogawa, T.; et al.; Bioor. Med. Chem. 1999, 7, 1743.