FDA accepts Lucassin filing for hepatorenal syndrome
This article was originally published in Scrip
The US FDA has accepted the final section of Orphan Therapeutics's NDA seeking approval of Lucassin (terlipressin) for the treatment of type 1 hepatorenal syndrome (HRS). The medicine has orphan drug status and fast track designation.
The rights for manufacturing and marketing the drug in North America were acquired by the US company Ikaria Holdings in September last year, and will be transferred to that company following marketing approval.
Lucassin is an injectable synthetic vasopressin analogue that interacts with the vasopressin V1 receptor, inducing vasoconstriction in the splanchnic area. This increases effective arterial volume, improves renal blood flow and thereby may improve renal function in patients with HRS.
The drug has been available in some countries outside the US for over 20 years, as Variquel and as Glypressin, for the treatment of bleeding oesophageal varices. It was launched recently in Austria, Germany and Switzerland for the treatment of type 1 HRS, but has not yet been approved for any indications in the US.
Type 1 HRS is a life-threatening disease that is characterised by rapid kidney failure and an increase in serum creatine levels. It is primarily associated with liver cirrhosis and is often precipitated by spontaneous bacterial peritonitis. Type 1 HRS has an average survival time of two to four weeks and a three-month mortality rate of more than 80%. There are no FDA approved drugs for the disease.
To date, the best treatment option for the disease is liver transplantation, which cures the underlying liver disease and allows renal function to recover. Other treatment options include hemodialysis, continuous renal replacement therapy and albumin infusion, but these are considered as temporary measures for patients while they await liver transplantation.
The accepted NDA is backed by two Phase III trials – OT-0401 and TAHRS. OT-0401 was a failed 112-subject trial that examined the proportion of patients with type 1 HRS alive at day 14 who demonstrated reversal of the disease as a primary endpoint. While the outcome was not statistically significant, there was a promising trend towards improvement, said the company (scripnews.com, August 9th 2006).
OT-0401 did, however, meet some secondary endpoints, showing a significant reduction in serum creatine in subjects receiving the drug compared with the placebo, for example.
TAHRS compared Lucassin with placebo in 46 patients. The drug significantly improved renal function, one of the primary endpoints, but failed to significantly improve three-month survival, another primary endpoint.