US FDA approves Mallinckrodt’s Terlivaz for injection to treat Hepatorenal Syndrome 

The US Food and Drug Administration (FDA) recently approved Mallinckrodt’s Terlivaz (terlipressin) for injection. It is the first and only FDA-approved product indicated to improve kidney function in adults with hepatorenal syndrome (HRS) with rapid reduction in kidney function, an acute and life-threatening condition requiring hospitalisation.

The FDA approval was based, in part, on results from the phase-III Confirm trial, the largest-ever prospective study (n=300) conducted to assess the safety and efficacy of Terlipressin in patients with HRS type 1 (HRS-1) in the US 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 (p=0.012).1 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, the annual meeting of AASLD. Results were also published in the New England Journal of Medicine in March of 2021. The Confirm trial was completed prior to the updated diagnostic criteria and terminology published in the 2021 AASLD guidance on hepatorenal syndrome, the statement added.

The most commonly observed adverse reactions in at least four per cent of patients treated with Terlivaz compared to placebo were abdominal pain reported in 19.5 percent (n=39) of patients (vs. 6.1%; n=6), nausea reported in 16 per cent (n=32) of patients (vs. 10.1%; n=10), respiratory failure reported in 15.5 per cent (n=31) of patients (vs. 7.1%; n=7) diarrhoea reported in 13 per cent (n=26) of patients (vs. 7.1%; n=7) and dyspnea reported in 12.5 per cent (n=25) of patients (vs. 5.1%; n=5).