The Food and Drug Administration (FDA) has approved Terlivaz® (terlipressin) injection to improve kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function.

Terlivaz is a vasopressin analogue selective for V1 receptors. The approval was based on data from the multicenter, double-blind, placebo-controlled, phase 3 CONFIRM trial (ClinicalTrials.gov Identifier: NCT02770716), which evaluated the efficacy and safety of terlipressin in patients with HRS type 1 (N=300) with rapidly progressive worsening of renal function.

At baseline, the mean serum creatinine (SCr) was 3.5mg/dL. According to the prescribing information, patients with a SCr of greater than 5mg/dL are unlikely to experience benefit from treatment.

Results showed that a greater proportion of patients in the terlipressin arm achieved the primary endpoint of Verified HRS Reversal compared with placebo (29.1% [n=58] vs 15.8% [n=16]; P =.012). Verified HRS Reversal was defined as the percentage of patients with 2 consecutive SCr values of less than or equal to 1.5mg/dL, obtained at least 2 hours apart while on treatment by day 14 or discharge.

Additionally, key secondary endpoints were met with 31.7% (n=63) of terlipressin-treated patients achieving durability of HRS reversal without renal replacement therapy (RRT) to day 30 compared with 15.8% (n=16) of placebo-treated patients (P =.003). Moreover, 33.3% (n=28/84) of terlipressin-treated patients with systemic inflammatory response syndrome achieved HRS Reversal, defined as SCr value of no more than 1.5mg/dL by day 14 or discharge, compared with 6.3% (n=3/48) of the placebo-treated patients (P <.001). 

As for safety, Terlivaz carries a Boxed Warning for serious or fatal respiratory failure. Patients with volume overload or with Acute-on-Chronic Liver Failure grade 3 are at increased risk of respiratory failure. Terlivaz should not be initiated in patients experiencing hypoxia (eg, oxygenation saturation less than 90%).

The most common adverse reactions reported with Terlivaz were abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.

“The FDA approval of Terlivaz is a significant milestone for Mallinckrodt as it brings an important treatment option to these critically ill patients requiring hospitalization and to US physicians who historically have had limited treatment interventions,” said Siggi Olafsson, President and CEO. “We’re excited to bring Terlivaz to US patients and physicians and plan to launch the product in the coming weeks.”

Terlivaz is supplied as a lyophilized powder containing 0.85mg of terlipressin in a single-dose vial.

References

  1. Mallinckrodt receives US FDA approval for Terlivaz® (terlipressin) for injection for the treatment of hepatorenal syndrome (HRS). News release. Mallinckrodt. Accessed September 14, 2022. https://www.prnewswire.com/news-releases/mallinckrodt-receives-us-fda-approval-for-terlivaz-terlipressin-for-injection-for-the-treatment-of-hepatorenal-syndrome-hrs-301624894.html
  2. FDA approves treatment to improve kidney function in adults with hepatorenal syndrome. News release. US Food and Drug Administration. Accessed September 14, 2022. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-improve-kidney-function-adults-hepatorenal-syndrome
  3. Terlivaz. Package insert. Mallinckrodt; 2022. Accessed September 14, 2022. https://mallinckrodt.com/globalassets/documents/corporate/ir/terlivaz-uspi-09-2022.pdf