The 8-7 decision allows Mallinckrodt to move forward with a Sept. 12 PDUFA date for the investigational agent.
The US Food and Drug Administration’s (FDA) Cardiovascular and Renal Drugs Advisory Committee has recommended the approval of terlipressin, an investigational agent aimed at treating adults with hepatorenal syndrome type 1 (HRS-1).
The 8-7 non-binding decision will allow Mallinckrodt to move forward with their FDA application for terlipressin, although its safety and efficacy has yet to be established by the FDA.
The review was based in part on the results of the phase 3 CONFIRM trial, the largest-ever prospective study (n = 300) to assess the safety and efficacy of terlipressin in patients with HRS-1.
Currently, there is no FDA approved treatment for HRS-1, a severe acute complication of patients who are suffering from end-stage liver disease. Previous treatments have been added to a standard of care regimen in this patient population, but there have been no successful efficacy studies regarding other treatment alternatives.
In an interview with HCPLive®, Michael P. Curry, MD, Section Chief of Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, who presented to the FDA explained why HRS-1 is so difficult to treat and why there has not been an FDA approved treatment to combat the life-threatening illness.
“First and foremost, the patients with HRS-1 are incredibly ill and it is a very challenging patient population to enroll in any clinical trial,” Curry said. “They have advanced stage liver disease and they have significant comorbid conditions, which makes it a difficult population of patients to study.”
HRS-1 currently requires a diagnosis of exclusion, but it is often difficult to diagnose in a timely manner.
Currently, if left untreated, the disease has a median survival time of about 2 weeks, with greater than 80% mortality within 3 months.
HRS-1 is estimated to affect between 30,000-40,000 in the US annually.
The treatment is designed to be taken in conjunction with intravenous albumin.
In April, the FDA accepted a New Drug Application (NDA) for terlipressin.
The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of Sept. 12 for the potential approval of terlipressin.
In 2018, researchers presented data from rom the REVERSE and OT-0401 trials, was presented at the American Association for the Study of Liver Diseases (AASLD) annual meeting (Liver Meeting) in San Francisco, showing terlipressin is linked to an improved overall and transplant-free survival in certain patients with HRS-1.
The data indicates that HRS-1 patients with lower baseline mean arterial pressure (MAP) responded significantly to terlipressin in instances observed in the randomized, double-blind, placebo-controlled trials.
Investigators pooled and analyzed 307 patients with HRS-1 for the post-hoc assessment. In both trials, patients received terlipressin or placebo plus albumin intravenously once every 6 hours for a maximum of 14 days. Investigators compared terlipressin and placebo in 2 variations of MAP rates: one with MAP <65 mm Hg, the other with MAP ≥65 mm Hg.
Overall survival at 90 days was significantly greater among the patients with MAP <65 mm Hg treated with terlipressin (68%) versus placebo (24%; P < .005). However, no overall survival difference at 90 days was observed among patients with ≥65 mm Hg (P = .429).