Summary

Plitidepsin (Aplidin) is a cyclic depsipeptide originally isolated from the marine tunicate Aplidium albicans and now produced synthetically by PharmaMar. It targets eukaryotic elongation factor 1A2 (eEF1A2), a host protein involved in translation elongation, exerting both anti-cancer and antiviral effects. Plitidepsin reached Phase 3 in relapsed/refractory multiple myeloma and gained attention during the COVID-19 pandemic as a potent host-directed antiviral, with in vitro potency against SARS-CoV-2 published in Science. It is conditionally approved in Australia for multiple myeloma but not approved by FDA or EMA. Research use only.

Mechanism

Plitidepsin binds to eukaryotic elongation factor 1A2 (eEF1A2), a host protein essential for translation elongation. In cancer cells, this binding disrupts protein synthesis and triggers apoptosis via caspase activation and oxidative stress. In the antiviral context, eEF1A2 is co-opted by viruses for replication; plitidepsin's host-directed action impairs viral replication across variants without directly targeting viral proteins, reducing the likelihood of resistance.

Evidence base

Phase 3 (ADMIRE, multiple myeloma): 255 patients, PFS 3.8 vs 1.9 months (HR 0.611, p=0.0048). FDA/EMA did not approve (Spencer et al., Leukemia, 2023).

COVID-19: In vitro IC50 ~0.88 nM against SARS-CoV-2 (White et al., Science, 2021). Phase 1/2 NEPLD trial showed faster viral clearance. Phase 3 ongoing.

Evidence grade: Moderate — Phase 3 data in myeloma (positive but not approved); promising but incomplete antiviral data.

Protocols

Multiple myeloma (Phase 3 ADMIRE):

  • Dose: 5 mg/m² IV infusion, days 1, 8, 15 of 4-week cycle
  • Combination: Dexamethasone 40 mg oral (days 1, 8, 15, 22)

COVID-19 (Phase 1/2 NEPLD):

  • Dose: 1.5 mg/m² IV daily for 3 days

⚠️ Research use only. Not for self-administration.

UK Status: Unlicensed (not approved by MHRA/EMA)

Plitidepsin is not licensed in the UK or EU. Conditional approval in Australia only (multiple myeloma). Not a controlled substance. Research-grade material legal for laboratory research. NHS access would require MHRA special import arrangements.

Vendor notes

Plitidepsin is an investigational compound not available from UK research peptide vendors. Laboratory-grade material available from chemical suppliers (e.g., Sigma-Aldrich, MedChemExpress). Verify purity via COAs.

References

  1. Spencer A, Lentzsch S, Weisel K, et al. Plitidepsin and dexamethasone vs dexamethasone alone in patients with relapsed/refractory multiple myeloma (ADMIRE): an international, randomised, controlled, phase 3 trial. Leukemia. 2023;37(3):556-565. doi:10.1038/s41375-022-01821-2
  2. White KM, Rosales R, Yildiz S, et al. Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science. 2021;371(6532):926-931. doi:10.1126/science.abd4085
  3. PharmaMar S.A. PharmaMar announces results from the ADMIRE Phase III clinical trial of plitidepsin in multiple myeloma. Press releases, 2017–2023.
  4. Alvarez R, López-Hernández FJ, Muñoz A. Plitidepsin: a novel marine-derived antitumoral agent. Invest New Drugs. 2008;26(5):457-463.
  5. NCT04784599 — Phase 1/2 NEPLD trial of plitidepsin in hospitalised COVID-19 patients. ClinicalTrials.gov.
  6. NCT04384066 — A Study of Plitidepsin in Participants With Moderate COVID-19. ClinicalTrials.gov.