Plitidepsin


Plitidepsin is a chemical compound extracted from the ascidian Aplidium albicans. It is currently undergoing clinical trial testing. It is a member of the class of compounds known as didemnins.

Chemical structure

Plitidepsin is a cyclic depsipeptide, meaning it is a cyclic peptide in which there is one or more ester bond in place of one or more of a peptide bond. Its chemical structure is very close to that of didemnin B, the only difference being that the lactate residue in didemnin B is present in the oxidized pyruvate version.

Pharmacological activity

Like all didemnin compounds, plitidepsin exhibits antitumor, antiviral and immunosuppressive activities. It shows promise in shrinking tumors in pancreatic, stomach, bladder, and prostate cancers.

Marketing authorisation status

European Union

In July 2003, plitidepsin was granted orphan drug status by the European Medicines Agency for treating acute lymphoblastic leukemia. On 14 December 2017, EMA´s Committee for Medicinal Products for Human Use adopted a negative opinion, recommending the refusal of the marketing authorisation for the treatment of multiple myeloma. PharmaMar requested a re-examination of the initial opinion. After a re-examination of the opinion, the refusal of the marketing authorisation was confirmed on 22 March 2018. The CHMP was of the opinion that the benefits of Aplidin did not outweigh its risks. Improvement in overall survival was not sufficiently demonstrated, and severe side effects were reported more frequently with the combination of Aplidin and dexamethasone than with dexamethasone alone.

Australia

In Australia plitidepsin was approved in December 2018, in combination with dexamethasone, for the treatment of patients with relapsed and refractory multiple myeloma who have received at least three prior treatment regimens, including both a proteasome inhibitor and an immunomodulator. It may be used after two prior lines of therapy if refractory and/or intolerant to both a proteasome inhibitor and an immunomodulator.

Clinical trials

As of 2007, it was undergoing multicenter phase II clinical trials.
In 2016, early results in a small phase I trial for multiple myeloma were announced.