Terlipressin Decision Delayed Due to Manufacturing Facility Change

In the CRL, the FDA stated that a satisfactory inspection is required before the NDA can be approved.

The Food and Drug Administration (FDA) has issued a second Complete Response Letter (CRL) to Mallinckrodt regarding the New Drug Application (NDA) for terlipressin for the treatment of adults with hepatorenal syndrome type 1 (HRS-1).

Terlipressin is a vasopressin analogue selective for V1 receptors. In July 2020, the FDA’s Cardiovascular and Renal Drugs Advisory Committee narrowly voted 8 to 7 in favor of the approval of terlipressin for HRS-1 based on data from the pivotal phase 3 CONFIRM trial (ClinicalTrials.gov Identifier: NCT02770716).

Results showed that the trial met its primary and key secondary end points demonstrating HRS reversal. Following the vote, Mallinckrodt received its first CRL from the FDA stating that the application could not be approved in its current form as more information was needed to support a positive risk-benefit profile.

The NDA was then resubmitted in August 2021 and a Prescription Drug User Fee Act date of February 18, 2022 was assigned to the application.

Due to a manufacturing facility change, the FDA once again issued a CRL as an inspection of the facility is required prior to making a decision on the NDA. According to the Company, the second letter did not cite any new safety or efficacy issues with terlipressin.

“We are working with the new facility to have it ready for inspection by the FDA,” said Steven Romano, MD, Executive Vice President and Chief Scientific Officer at Mallinckrodt. “We remain committed to this critically ill patient population, who currently have no approved treatment option in the US for HRS, and we believe that there is a path to approval in 2022.”


Mallinckrodt provides a regulatory update on terlipressin. News release. Mallinckrodt plc. Accessed February 22, 2022. https://www.prnewswire.com/news-releases/mallinckrodt-provides-a-regulatory-update-on-terlipressin-301486983.html.