Aplidin (plitidepsin) is an investigative anticancer agent under development by PharmaMar, a pharmaceutical company that commercializes anticancer drugs of marine origin. Aplidin is isolated from the sea squirt (Aplidium albicans) and has shown anti-myeloma activity even in myelomas resistant to other agents. The drug has received orphan drug designation in the U.S., the European Union, and Switzerland. The target of plitidepsin is the eEF1A2 protein. The bonding of plitidepsin to this protein blocks its pro-oncogenic property and impedes the transportation of the misfolded proteins, which are toxic to the tumor, to the proteasome for their destruction. It also inhibits the activation of the aggresome by eEF1A2 and the destruction of the aggresome in the lysosome. This provokes anexcess of misfolded proteins, this causing cell death through apoptosis. Recently, a Phase III randomized trial in patients with relapsed/refractory multiple myeloma reported outcomes for plitidepsin plus dexamethasone compared with dexamethasone. Median progression-free survival was 3.8 months in the plitidepsin arm and 1.9 months in the dexamethasone arm. However, on 14 December 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of the marketing authorisation for the medicinal product Aplidin, intended for the treatment of multiple myeloma. At the time of the initial review, the CHMP was concerned that the data from the main study showed only a modest increase of around one month in the time patients given Aplidin lived without their disease getting worse, compared with those treated with dexamethasone alone. In addition, improvement in overall survival (how long patients lived overall) was not sufficiently demonstrated. Regarding safety, severe side effects were reported more frequently with the combination of Aplidin and dexamethasone than with dexamethasone alone. Based on the above, the CHMP was of the opinion that the benefits of Aplidin did not outweigh its risks and recommended that it be refused marketing authorisation.After re-examination, the Committee remained of the same opinion. The CHMP therefore confirmed its recommendation that the marketing authorisation be refused.