FDA CRL - Orphan Therapeutics, LLC

The FDA issued a Complete Response Letter (CRL) to Orphan Therapeutics, LLC for its New Drug Application (NDA 022231) concerning Lucassin (terlipressin) injection, 1 mg, intended for hepatorenal syndrome (HRS) type I. Under section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act, the application was deemed unapprovable in its current form due to several critical deficiencies.

Primary issues included inadequate clinical and statistical data; two submitted studies failed to demonstrate statistically significant efficacy for HRS type I using pre-specified endpoints. The proposed 14-day treatment regimen lacked sufficient safety data, and concerns were raised regarding the occurrence of serious adverse events. Additionally, data collection for vital signs and laboratory parameters in the trials was insufficient. Product quality deficiencies related to drug substance specifications, heavy metal testing, and the residual solvent analytical method were also noted. Labeling issues required revisions to the draft content and specific carton and vial details. Lastly, satisfactory resolution of deficiencies observed during recent manufacturing facility inspections is mandated.

Orphan Therapeutics must conduct at least one additional, well-controlled study to definitively demonstrate efficacy and safety for HRS type I, meeting statistical significance with pre-specified endpoints. The FDA offered to discuss trial designs. The company is also required to resolve all product quality and labeling issues, address manufacturing site deficiencies, and provide a comprehensive safety update.