Plitidepsin: an orphan drug

Abstract

Introduction: Plitidepsin (Aplidin®) is a second-generation didemnin compound that belongs to drugs derived from natural oceanic products.

Areas covered: In this review, the authors present the preclinical and clinical data available on this specific marine drug. In vitro and in vivo experiments showed that plitidepsin was active against many tumor models and was able to induce cell cycle arrest at low doses, apoptosis and also had antiangiogenic properties suggesting that this drug may be active in a broad range of human tumors. Phase I trials showed that the drug could be administrated in short or prolonged infusions, with a safety profile much more acceptable than the parent didemnin B molecule. Dose-limiting toxicities were hepatic (cytolysis) and muscular, but were manageable and reversible. No significant bone marrow toxicity was observed. Clinical activity was observed in many tumor types in Phase I that was not reproducible in a high proportion of cases in Phase II.

Expert opinion: In hematology, plitidepsin is active in peripheral T-cell lymphomas (ORR 20.7%), but not in B-cell lymphomas suggesting a specific activity in T-cell proliferation especially in AILD where complete remissions were observed in monotherapy. Given the safety profile of this drug, combination trials could be further tested in this rare and serious lymphoma entity.

Keywords::

• Aplidin®
• didemnin
• marin compound
• plitidepsin
• T-cell lymphoma

Acknowledgement

A Danu and C Willekens equally contributed to this work.