Date: 2018-06-28
Type of information: Granting of a Market Authorisation in the EU
Product name: Jinarc®
Compound: tolvaptan
Therapeutic area: Rare diseases - Kidney diseases - Renal diseases
Action mechanism:
- vasopressin receptor 2 antagonist. Tolvaptan is a selective, competitive vasopressin receptor 2 antagonist. Tolvaptan acts by blocking receptors in the kidneys to which the hormone vasopressin attaches, which regulates the level of water and sodium in the body. In ADPKD, it is thought that kidney cells do not respond normally to vasopressin, leading to the formation of fluid-filled cysts. By blocking vasopressin receptors in the kidneys, Jinarc can slow down cyst formation.
Company: Otsuka Pharmaceutical (Japan)
Disease: autosomal dominant polycystic kidney disease
Latest news:
- • On June 28, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Inovelon®. The CHMP adopted an extension to the existing indication as follows:
"Inovelon® is indicated as adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut
syndrome in patients 41 years of age and older."
- • On 26 February 2015, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Jinarc®, 15 mg, 30 mg, 45 mg, 60 mg and 90 mg tablets intended to slow the progression of cyst development and renal insufficiency of autosomal dominant polycystic kidney disease (ADPKD) in adults with CKD stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease. Jinarc® was designated as an orphan medicinal product on 5 August 2013.
- The benefits with Jinarc® are its ability to slow the progression of cyst growth and renal insufficiency in adult patients with ADPKD with stage 1 to 3 at initiation of treatment with evidence of rapidly progressing disease. In the pivotal trial the rate of total kidney volume (TKV) increase over 3 years could be shown to be significantly less for tolvaptan-treated patients than for subjects receiving
placebo: 2.80% per year vs 5.51% per year, respectively (ratio of geometric mean 0.974; 95% CI 0.969 to 0.980; p < 0.0001).
- Events on worsening of kidney function (25% reduction in reciprocal serum creatinine during treatment) were 61.4% less likely for tolvaptan compared with placebo (hazard ratio, 0.39; 95% CI, 0.26 to 0.57; nominal p <0.0001). Tolvaptan was also associated with a slowing of decline in kidney function by 32% compared with placebo (reciprocal of the serum creatinine level, ?2.61 [mg/mL]?1 per year vs. ?3.81 [mg/mL]?1 per year; p<0.001) showing relevant effects on renal function decline in secondary endpoints of the pivotal study.The most common side effects are deriving from its aquaretic effects. These included thirst, polyuria, nocturia, and pollakiuria occurring in approximately 55%, 38%, 29% and 23% of patients, respectively. Furthermore, tolvaptan has been associated with idiosyncratic elevations of blood alanine and aspartate aminotransferases (ALT and AST) with infrequent cases of concomitant elevations in total bilirubin (BT). A pharmacovigilance plan for Jinarc® will be implemented as part of the marketing authorisation. It is proposed that Jinarc® must be initiated and monitored under the supervision of physicians with expertise in managing ADPKD and a full understanding of the risks of tolvaptan therapy including hepatic toxicity and monitoring requirements.
- Tolvaptan is already authorised in the EU for treating hyponatraemia (abnormally low sodium levels) although the doses studied in ADPKD are different.
- • On December 27, 2013, Otsuka Pharmaceutical has announced that the European Medicines Agency (EMA) has accepted the submission of a marketing authorisation application (MAA) for the potential approval 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. In Japan, the application for ADPKD is currently under review. In the United States, Otsuka and FDA have been working together to determine the most appropriate path forward to allow tolvaptan to be available for patients suffering from ADPKD.
- • On 9-11 July 2013, the Committee for Orphan Medicinal Products (COMP) has recommended the granting of an orphan designation for tolvaptan for treatment of autosomal dominant polycystic kidney disease.
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2009-05-19
UE authorization: 2015-05-27
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA: 2012-04-06
Orphan status UE: 2013-08-05
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
