Terlipressin: Longer Peptide Effect Half-Life via an Active Metabolite

On Monday, Mar. 27th (12:15 PM ET), our Drug Hunter team will be sponsoring a luncheon at ACS Spring 2023 in Indianapolis with a presentation on scientific gems from 2022’s drug approvals (request an invitation here). Each newly approved drug has an interesting scientific story, and you can see our overview of all 36 of the novel small molecule and large molecule FDA approvals for 2022 here.

One we haven’t discussed in detail yet is the peptide prodrug, terlipressin. Terlipressin (Terlivaz) is a synthetic analog of the natural hormone, vasopressin, that was approved in Sep. 2022 for hepatorenal syndrome. Given how challenging it is to improve the PK of peptide drugs, this molecule is an interesting example of a synthetic peptide with significantly longer activity than the corresponding natural hormone. This article briefly summarizes the history of the molecule, the concerns around the molecule leading up to its approval, how it’s different from vasopressin, and more!

Terlipressin (Terlivaz)

Dosing: 0.85 mg IV every 6 hours (may be increased to 1.7 mg IV every 6 hours if serum creatinine levels on Day 4 has decreased by 30% from baseline)
Indication: hepatorenal syndrome
Marketer: Mallinckrodt Pharmaceuticals
Originator: Czech Academy of Sciences (US3980631A, 1974)
Expiration: 2037
Projected Sales: $300M
Pivotal Trials: CONFIRM, 300 patients
Designations: Priority Review, Fast Track, Orphan