The Food and Drug Administration (FDA) has issued a 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 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. Results showed that terlipression met the primary and key secondary end points demonstrating HRS reversal. 

However, in meeting documents, the FDA committee noted that an exploratory analysis of treatment effects on clinical outcomes showed terlipressin was not associated with improved survival compared with placebo. The committee also raised safety concerns regarding respiratory failure events. 

In the CRL, the FDA stated that the application could not be approved in its current form and that more information to support a positive risk-benefit profile was needed. 

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“While we are disappointed that the FDA issued a Complete Response Letter for terlipressin, we remain confident in the strength of the data from our phase 3 CONFIRM study, which is the largest clinical trial ever conducted in this rare condition,” said Steven Romano, MD, Executive Vice President and Chief Scientific Officer at Mallinckrodt. “We are surprised by and disagree with the FDA’s decision and remain committed to pursuing all available options as we continue working with the FDA toward approval of terlipressin in order to help address this difficult and life-threatening syndrome.”

Terlipressin is currently approved for the treatment of HRS-1 in several other countries outside of the US.

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Mallinckrodt receives a Complete Response Letter from the US Food and Drug Administration (FDA) for terlipressin for the treatment of hepatorenal syndrome type 1 (HRS-1). Accessed September 14, 2020.