Aplidin

Analyst Outlook

Aplidin (plitidepsin) is a cyclic depsipeptide antitumor agent developed by the Spanish company

PharmaMar. In 2004, Aplidin gained orphan drug designation in the US and EU for the treatment of

multiple myeloma (MM), and it is currently in Phase III development for the disease. PharmaMar is

positioning it as a fourth-line therapy for heavily pretreated MM patients in combination with

dexamethasone. Targeting fourth-line therapy will significantly limit the potential share for Aplidin in

the MM market. Datamonitor Healthcare also believes that Aplidin will face strong competition from

existing therapies with proven efficacy in heavily pretreated patient groups.

Drug Overview

Aplidin is an intravenous, marine-originated cyclic depsipeptide antitumor agent. The drug, which is

currently synthesized chemically, was originally isolated from the marine tunicate Aplidium albicans

(Cuadrado et al., 2003; PharmaMar, 2014). Aplidin’s exact mechanism of action is not fully

understood, but it is believed to induce cytotoxicity through several pathways. It has been shown to

inhibit the cancer-associated Eukaryotic elongation factor 12 (eEF1A2) (PharmaMar press release,

2015; Lee and Surh, 2009), as well as disrupting the glutathione homeostasis and activating mitogen-
activated protein kinases, leading to caspase-dependent apoptosis (García-Fernández et al., 2002;

González-Santiago et al., 2006). Aplidin has also been shown to block cell division in the G1/G2 phase,

and inhibit the secretion of vascular endothelial growth factor (Biscardi et al., 2005; Erba et al., 2002).