FDA Approves Mallinckrodt’s Terlivaz for injection for Treatment of Hepatorenal Syndrome

The U.S. Food and Drug Administration approved Mallinckrodt’s Terlivaz for injection, the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function, an acute and life-threatening condition requiring hospitalization.

Hepatorenal syndrome (HRS) involving rapid reduction in kidney function is an acute and life-threatening condition that occurs in people with advanced liver disease. HRS is classified into two distinct types—a rapidly progressive type that leads to acute renal failure where patients are typically hospitalized for their care and a more chronic type that progresses over weeks to months. HRS involving rapid reduction in kidney function is estimated to affect between 30,000 and 40,000 Americans annually. If left untreated, HRS with rapid reduction in kidney function has a median survival time of approximately two weeks and greater than 80 percent mortality within three months.

“The FDA approval of Terlivaz (terlipressin) is a significant milestone for Mallinckrodt as it brings an important treatment option to these critically ill patients requiring hospitalization and to U.S. physicians who historically have had limited treatment interventions,” said Siggi Olafsson, president and CEO of Mallinckrodt.

Terlipressin is one of the most studied pharmacological agents in HRS with more than 70 published manuscripts and presented abstracts on clinical data to date. It has been approved outside the U.S. for more than 30 years and is available on five continents for its indications in the countries where it is approved.

The FDA approval was based, in part, on results from the phase 3 CONFIRM trial, the largest-ever prospective study conducted to assess the safety and efficacy of terlipressin in patients with HRS type 1 (HRS-1) in the U.S. and Canada. The CONFIRM trial met its primary endpoint of Verified HRS Reversal, defined as renal function improvement, avoidance of dialysis and short-term survival. To achieve Verified HRS Reversal, patients had to have two consecutive serum creatinine (SCr) values of ≤1.5 mg/dL, at least two hours apart by day 14 or hospital discharge. To be included in the primary efficacy endpoint analysis, patients had to be alive and without intervening renal replacement therapy (e.g., dialysis) at least 10 days after achieving Verified HRS Reversal. Initial results were presented in a late-breaking session at The Liver Meeting 2019. Results were also published in the New England Journal of Medicine in March of 2021.

“Diagnosing and treating HRS can be challenging, and every minute counts when managing patients who have it,” said Steven Romano, executive vice president and chief scientific officer at Mallinckrodt. “Terlivaz gives U.S. physicians the first FDA-approved option for treating HRS patients with rapid reduction in kidney function that may help them improve kidney function and lessen the associated need for renal replacement therapy, such as dialysis.”

The most commonly observed adverse reactions in at least 4 percent of patients treated with Terlivaz compared to placebo were abdominal pain reported in 19.5 percent (n=39) of patients, nausea reported in 16 percent (n=32) of patients, respiratory failure reported in 15.5 percent (n=31) of patients, diarrhea reported in 13 percent (n=26) of patients, and dyspnea reported in 12.5 percent (n=25) of patients.

The FDA approval also comes with a Black Box warning that Terlivaz can cause serious, life-threatening respiratory failure.

Terlivaz is expected to be available in the U.S. in the coming weeks.

Photo: Siggi Olafsson, president and CEO of Mallinckrodt

Author: Rare Daily Staff