First-Ever Treatment Approved in Canada for Adults Living with ADPKD, a Life-Threatening Kidney Disease

JINARC^TM slows the progression of kidney enlargement in patients with autosomal dominant polycystic kidney disease (ADPKD), which should help protect the kidneys from damage and failure

• JINARC^TM (tolvaptan) is the first pharmaceutical treatment available in Canada for patients with ADPKD. JINARC™ was discovered in Japan by Otsuka Pharmaceutical and was first approved there for the treatment of ADPKD in 2014.
• The Health Canada approval of JINARC™ is based on the results of the pivotal Phase 3 randomized, double-blind and placebo-controlled TEMPO 3:4 Trial, the largest study conducted to date in adults with ADPKD.¹
• ADPKD is a chronic and progressive genetic disease, which causes cyst growth in the kidneys, leading to an increase in total kidney volume, resulting in complications that include chronic and acute pain, hypertension and kidney failure.²
• ADPKD impacts approximately 35,000 Canadians³ and affects people regardless of gender, age, race or ethnic origin.⁴

TOKYO--(BUSINESS WIRE)--Otsuka Pharmaceutical Co., Ltd. and its affiliate Otsuka Canada Pharmaceutical Inc. announce that Health Canada has approved JINARC™ (tolvaptan) as the first pharmaceutical agent for the treatment of autosomal dominant polycystic kidney disease (ADPKD). JINARC™ is indicated to slow the progression of kidney enlargement by targeting the underlying pathophysiology of the disease.

The Health Canada approval of JINARC™ is based on the results of the pivotal Phase 3 randomized, double-blind and placebo-controlled TEMPO 3:4 Trial, which is the largest, Phase 3 study conducted to date in adults with ADPKD.⁵

Dr. Sanjay Pandeya, a nephrologist in the Toronto area commented, “Many patients with ADPKD suffer severe pain as the kidneys develop a larger cyst burden. Other organs may also be impacted and kidney failure is a reality in many patients. This can significantly affect overall health and quality of life. The approval of JINARC™ marks a significant advancement in the previously bleak landscape of therapeutics for ADPKD – patients now have an option that can reduce the development of cyst formation, improve symptom control, and potentially delay the progression of this serious disease.”

JINARC™ was developed over a period of 26 years through the persevering efforts of researchers in Otsuka’s Japanese pharmaceutical research center. Upon discovering a cell signaling pathway that causes renal cysts to proliferate and enlarge,⁶ Otsuka launched an effort in 2004 to develop a drug for the disease in conjunction with the world’s leading ADPKD medical specialists.

ADPKD impacts approximately 35,000 Canadians⁷ and affects people regardless of gender, age, race or ethnic origin.⁸ Approximately, half of polycystic kidney disease (PKD) patients reach end stage renal disease (ESRD) and require renal replacement therapy in the form of dialysis or a kidney transplant by age 54.⁹

“ADPKD is one of the most common, life-threatening, genetic diseases and yet until now, patients have been without a treatment option for the progression of the disease,” says Jeff Robertson, Executive Director, PKD Foundation of Canada. “With a mother and grandmother impacted by ADPKD, our family knows just how life-changing a treatment like this will be for the PKD community.”

About the TEMPO 3:4 Trial

The TEMPO 3:4 Trial was conducted over three years in a total of 1,445 adult patients with early, rapidly progressing ADPKD. In order to select patients who might best benefit from the effects of JINARC™, clinical trials evaluated ADPKD patients having enlarged kidneys and relatively preserved renal function at the time of initiation of treatment. In the TEMPO 3:4 Trial, JINARC™ achieved its primary endpoint, demonstrating a statistically significant reduction of almost half (49%) the annual increase in total kidney volume (TKV) versus placebo (p<0.001). Furthermore, the study showed JINARC™ significantly reduced the decline in kidney function by 30% versus placebo (p<0.001).¹⁰

The most commonly reported adverse reactions, consistent with the pharmacologic activity of JINARC™ are thirst, polyuria (excessive production of urine), nocturia (waking up during the night in order to urinate), and pollakiuria (frequent daytime urination) occurring in approximately 55%, 38%, 29% and 23% of patients, respectively. In a small percentage of patients receiving JINARC™ (4%) there were adverse events potentially associated with liver injury. As there are no predictive factors as to which patients receiving JINARC™ will experience liver injury, all patients on JINARC™ will be monitored. To help mitigate the risk of liver injury, blood testing for liver enzymes is required prior to initiation of JINARC™, then continuing monthly for 18 months, every 3 months for the next 12 months, and then every 3 to 6 months thereafter during treatment. JINARC™ will only be available through a hepatic safety monitoring and distribution program administrated by Otsuka Canada Pharmaceutical Inc. and managed in conjunction with patients’ treating physicians.¹¹

About JINARC™ (tolvaptan)

JINARC™ is a selective vasopressin V2-receptor antagonist and is indicated to slow the progression of kidney enlargement in patients with ADPKD. Vasopressin is a hormone normally responsible for maintaining water balance by stimulating water re-absorption in the kidney. Vasopressin levels are higher than normal in people with ADPKD. The high level of vasopressin promotes cyst growth, which increases the size of the kidneys.¹² JINARC™ works by blocking the effects of vasopressin, which can slow down the rate at which cysts – and therefore kidneys – grow. This should help protect kidneys from damage and failure.¹³ JINARC™, a twice-daily, oral medication,¹⁴ is expected to become available to eligible patients in Canada in May 2015.

About ADPKD

ADPKD is the most common, inherited kidney disease and is primarily characterized by the development and expansion of multiple fluid-filled cysts in the kidney. As a result of cyst growth, kidneys become significantly enlarged and, over time, kidney function deteriorates. The genetic mutation that causes ADPKD is a dominant trait meaning only one parent needs to be affected for their child to have a 50 per cent chance of inheriting the disease.¹⁵ According to a recent survey, on average, two-thirds of ADPKD patients have other family members who have been diagnosed with the disease. Furthermore, the majority of ADPKD patients say that the disease has impacted their ability to: complete every day activities (i.e., running errands, spending time with family) (64 per cent), travel and go on vacation (62 per cent) and lead a healthy and active lifestyle (59 per cent).¹⁶*

*Given the low incidence population and the small sample size for this hard to reach group, results should be interpreted directionally and with caution.

About Otsuka Pharmaceutical Co., Ltd.

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 and original products, with a focus on pharmaceutical products for the treatment of diseases and nutraceutical products for the maintenance of everyday health.

In pharmaceuticals, Otsuka is a leading firm in the challenging area of mental health and also has research programs for several under-addressed diseases including tuberculosis, a significant global public health issue. These commitments illustrate more powerfully than words how Otsuka is a “big venture” company at heart, applying a youthful spirit of creativity in everything it does.

About Otsuka Canada Pharmaceutical Inc.

Otsuka Canada Pharmaceutical Inc. (OCPI) is an innovative, fast-growing healthcare company that commercializes Otsuka medicines in Canada, with a focus on neuroscience, nephrology, oncology and cardiovascular health. OCPI is dedicated to improving patients' health and the quality of human life. OCPI was established in 2010, with headquarters in Saint-Laurent, Québec.

References

¹ JINARC Canadian product monograph. Otsuka Canada Pharmaceutical Inc. Updated: February 23, 2015.
² Grantham, Jared J. Does extended-release somatostatin slow the growth of renal cysts in autosomal-dominant polycystic kidney disease? Nature Clinical Practice Nephrology. 2006: 66-67.
Torres VE, Harris PC et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. The New England Journal of Medicine. 2012;367 (25): 2407-2418
³ The Kidney Foundation of Canada. Polycystic kidney disease (PKD). Accessed January 2015. http://www.kidney.ca/page.aspx?pid=329
⁴ The PKD Foundation of Canada. Just diagnosed. Accessed 2015. http://endpkd.ca/learn/learn-about-adpkd/just-diagnosed/
⁵ JINARC Canadian product monograph. Otsuka Canada Pharmaceutical Inc. Updated: February 23, 2015.
⁶ 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
⁷ The Kidney Foundation of Canada. Polycystic kidney disease (PKD). Accessed January 2015. http://www.kidney.ca/page.aspx?pid=329
⁸ The PKD Foundation of Canada. Just diagnosed. Accessed 2015. http://endpkd.ca/learn/learn-about-adpkd/just-diagnosed/
⁹ Alam, Ashan and Perrone, Ronald D.,Management of ESRD in patients with autosomal dominant polycystic kidney disease. Advances in Chronic Kidney Disease, Vol 17, No 2. March 2010: pp 164-172.
¹⁰ JINARC Canadian product monograph. Otsuka Canada Pharmaceutical Inc. Updated: February 23, 2015.
¹¹ Ibid.
¹² Ibid.
¹³ Ibid.
¹⁴ Ibid.
¹⁵ The Kidney Foundation of Canada. Polycystic kidney disease (PKD). Accessed January 2015. http://www.kidney.ca/page.aspx?pid=329
¹⁶ The “ADPKD – Quality of life patient study” was conducted through an online survey by Vision Critical between November 21, 2014 and February 9, 2015, with 58 Canadian adults who currently have ADPKD. A probability sample of ADPKD patients of the same size would yield a margin of error of +/- 13%.