FDA Panel Votes 8-7 in Favor of Mallinckrodt's HRS-1 Drug

Shares of Mallinckrodt climbed after the company announced the Cardiovascular and Renal Drugs Advisory Committee of the U.S. Food and Drug Administration voted to recommend approval for its investigational agent terlipressin to treat adults with hepatorenal syndrome type 1.

The drug narrowly passed through the panel in an 8 to 7 vote. The panel suggested that the benefits of terlipressin outweigh the safety risks associated with the drug. During Phase III testing, serious adverse events were reported in 65% of subjects in the terlipressin group and 60.6% in the placebo group.

The terlipressin New Drug Application is based, in part, on results from the Phase III CONFIRM trial, the largest-ever prospective study conducted in patients with HRS-1. The CONFIRM trial met its primary endpoint of Verified HRS Reversal (VHRSR), defined as renal function improvement, avoidance of dialysis and short-term survival. Study results, which were presented in November at the American Association for the Study of Liver Diseases, showed 29.1% of patients who received terlipressin plus albumin achieved Verified HRS Reversal in comparison to 15.8% who received placebo plus albumin. Additionally, 36.2% of patients who received terlipressin demonstrated a reversal of HRS within 14 days of drug administration. That was in comparison to 16.8% for placebo patients.

Hepatorenal syndrome type 1 (HRS-1) is an acute and life-threatening syndrome involving acute kidney failure in people with cirrhosis. The condition has a median survival time of less than two weeks and greater than 80% mortality within three months if left untreated, Mallinckrodt said. The disorder is estimated to impact between 30,000 and 40,000 Americans annually. There are currently no approved treatments for HRS-1 in the United States.

Terlipressin is a potent vasopressin analog selective for V1 receptors. It has been approved to treat HRS-1 outside of the United States.

Although terlipressin narrowly passed the advisory committee, Mallinckrodt said it was pleased the drug is moving closer to possible approval from the regulatory agency. Steven Romana, Mallinckrodt’s chief scientific officer, said there is potential clinical value in what terlipressin can provide to HRS-1 patients.

“We acknowledge the clinical challenges associated with treating this complex disease in such a critically ill patient population. We are committed to working closely with the FDA as it continues to review our application,” Romano said in a statement.

The agency assigned a Sept. 12 Prescription Drug User Fee Act (PDUFA) target date for terlipressin. The FDA is not bound by the recommendations of the advisory committee but often sides with the results.