Aplidin (plitidepsin) / Megapharm, TTY Biopharm, PharmaMar, Boryung Group, Roche, Specialised Therap - LARVOL DELTA

THALASSA: Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults With Post-COVID-19 Condition (PCC) (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: Fundacin FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promocin de la Salud y la Ciencia | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2026 ➔ Sep 2026

Enrollment closed • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease

Plitidepsin induces apoptosis in glioma cells through β-TrCP-mediated ubiquitination and degradation of BMI1. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "These findings identify plitidepsin as a potent inducer of β-TrCP-dependent BMI1 degradation, unveiling a novel mechanism linking BMI1-NOXA axis activation to intrinsic apoptosis in gliomas. This study highlights plitidepsin's therapeutic potential for glioma treatment through targeting the ubiquitin-proteasome pathway."

Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • Targeted Protein Degradation • BMI1 • CASP3 • PMAIP1

Extending the Targets for Coronavirus Antivirals Beyond That of Approved Drugs: Insights From Preclinical Research. (PubMed, Microb Biotechnol) - "A chemoinformatic search found inhibitors for the interaction of NSP9 with host elongation factor eIF4A and for NSP13 with elongation factor eEF1A. Plitidepsin, a clinically used eEF1A inhibitor, was tested in human clinical trials with COVID-19 patients demonstrating in vivo antiviral activity and a trend for clinical amelioration in an underpowered phase 3 clinical trial."

Journal • Preclinical • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • EEF1A1 • EIF4A1 • EIF4A2

Comprehensive investigation of SARS-CoV-2 intestinal pathogenesis in Drosophila. (PubMed, iScience) - "Treatment with Plitidepsin, a COVID-19 drug candidate, mitigates most SARS-CoV-2 pathogenic features in both the Drosophila midgut and human pulmonary cells, while modulating basal lipid droplet homeostasis in uninfected conditions. These findings establish the Drosophila midgut as a potent model for studying SARS-CoV-2 GI pathogenesis and evaluating antiviral compounds."

Journal • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

THALASSA: Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults With Post-COVID-19 Condition (PCC) (clinicaltrials.gov) - P2 | N=90 | Active, not recruiting | Sponsor: Fundacion Fls De Lucha Contra El Sida Las Enfermedades Infecciosas Y La Promocion De La Salud Y La Ciencia | Recruiting ➔ Active, not recruiting | Active, not recruiting ➔ Recruiting

Enrollment closed • Enrollment open • Infectious Disease • Novel Coronavirus Disease

THALASSA: Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults With Post-COVID-19 Condition (PCC) (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia | Trial completion date: Jun 2026 ➔ Sep 2026

Trial completion date • Infectious Disease • Novel Coronavirus Disease

Marine-Derived Anticancer Compounds and their Clinical Status. (PubMed, Anticancer Agents Med Chem) - "Marine sources offer a wide variety of compounds, and modifying them provides researchers with new opportunities for drug development. Many marine-derived compounds have already shown strong pharmacological effects, with some even proven in clinical use. New studies suggest that marine compounds could also play an important role in anticancer drug delivery systems, making them a promising option for future treatments."

Journal • Oncology

Exploring marine-derived compounds as potential anti-cancer agents: Mechanisms and therapeutic implications. (PubMed, Cancer Pathog Ther) - "Notably, marine-derived drugs such as trabectedin, eribulin, and plitidepsin have received regulatory approval for the treatment of various malignancies, demonstrating the translational potential of these natural compounds. It also emphasizes the need for deeper insights into their molecular targets and the potential for synergistic use with existing chemotherapeutic agents. Future directions should focus on exploring untapped marine biodiversity, developing eco-friendly harvesting strategies, and developing innovative delivery platforms to fully harness the therapeutic promise of the marine pharmacopeia in oncology."

Journal • Review • Oncology

Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma. (PubMed, Ann Hematol) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in relapsed/refractory multiple myeloma: Results for patients aged < 75 years (ASH 2025) - "Tolerance to treatment was also evaluated by the time to performance status deterioration or death, indicative of patient general status, which was 5.7 months (95%CI, 3.8-9.0 months) for the plitidepsin plus DXM arm and 2.1 months (95%CI, 1.4-3.8 months) for the DXM arm (HR=0.5680; 95%CI, 0.394-0.820; p=0.0021). In conclusion, larger differences in efficacy outcomes while maintaining a similar safety profile together with a novel mechanism of action suggest that this combination can be a valid option for patients with r/r MM aged < 75 years."

Clinical • Combination therapy • P3 data • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain

Plitidepsin in combination with dexamethasone (ADMYRE trial) versus an external control arm of pomalidomide plus dexamethasone in patients with relapsed/refractory multiple myeloma (ASH 2025) - "Safety profile of POM+LD-DXM was associated to a higher rate of AEs, as expected for a combination. In conclusion, P+LD-DXM can be considered an alternative therapeutic option in r/r MM as this comparison in terms of OS shows that P+LD-DXM is non-inferior to POM+LD-DXM with an advantageous safety profile in terms of hematological and infection events."

Clinical • Combination therapy • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Thrombocytopenia

Can plitidepsin be used as an antiviral against RSV? (PubMed, mSphere) - "So, we think that our results are new and original and that this information should be useful for the community working either with plitidepsin or eEF1A, with viruses, or other topics. We think that, in contrast to what is suggested by previous studies, it is risky to use plitidepsin as an antiviral in humans."

Journal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • EEF1A1

Pharmacological reprogramming of plitidepsin as a SARS-CoV-2 inhibitor. (PubMed, Mol Aspects Med) - "The pharmacokinetic and pharmacodynamic data on plitidepsin will be analyzed, and the various experimental lines of evidence in support of the molecule's multifactorial mechanism of action will be explored. Finally, the available data on the use of plitidepsin in patients with COVID-19 will be presented, including results from a Phase I proof-of-concept study, real-world data from immunocompromised patients, and a look of results from a Phase III clinical trial that confirms the working hypothesis."

Journal • Review • Hematological Malignancies • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed/Refractory Multiple Myeloma: Results for Patients Aged <75 Years. (PubMed, Cancers (Basel)) - "The most common adverse events (all grades) related to the study treatment in patients < 75 years were fatigue (39.2% of patients), gastrointestinal (nausea, 39.2%; vomiting, 19.6%; diarrhea, 14.7%), and myalgia (14.0%). Larger differences in efficacy outcomes while maintaining a similar safety profile, together with a novel mechanism of action, suggest that this combination can be a valid option for patients with r/r MM aged <75 years."

Journal • P3 data • Fatigue • Hematological Malignancies • Multiple Myeloma • Musculoskeletal Pain • Oncology • Pain

Randomized Phase III Study (ADMYRE) of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Relapsed/Refractory Multiple Myeloma: Results for Patients Aged <75 Years (Multidisciplinary Digital Publishing Institute) - "Compared to the overall ADMYRE population, a higher reduction was found with plitidepsin plus DXM for the risk of progression or death in the primary endpoint: 47.7% vs. 35.0% (Hazard ratio [HR] = 0.523 vs. HR = 0.6509). Higher reduction in the risk of death was also found (28.9% vs. 20.3%; HR = 0.711 vs. HR = 0.797), with a clinically meaningful 5-month difference in median overall survival (13.0 months vs. 8.1 months; p = 0.0350)."

P3 data • Multiple Myeloma

Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics. (PubMed, Mar Drugs) - "This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin)...Pharmacokinetic challenges and structure-activity relationships are critically analyzed, emphasizing nanodelivery systems and synthetic analog development. This review bridges mechanistic insights with translational potential, offering a cohesive framework for future drug development."

Journal • Review • Atherosclerosis • Cardiovascular • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Oncology • Renal Disease

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 21-24 July 2025 (European Medicines Agency) - "PharmaMar withdrew its application for a marketing authorisation of Aplidin for the treatment of multiple myeloma. The company withdrew the application on 23 July 2025 during a re-examination."

European regulatory • Multiple Myeloma

Functional characteristics of plitidepsin as an antiviral treatment against monkeypox virus infection. (PubMed, Antiviral Res) - "Additionally, the limited efficacy of current smallpox antivirals, such as Tecovirimat and Brincidofovir, alongside growing concerns about the emergency of tecovirimat resistance mutants, underscores the need for new therapeutic options. These findings indicate plitidepsin as a promising candidate for mpox treatment. Further studies are needed to explore its potential as a standalone or combination therapy, supporting clinical evaluation for mpox treatment."

Journal • Infectious Disease • Oncology • EEF1A1

Comprehensive investigation of SARS-CoV-2 intestinal pathogenesis in Drosophila. (PubMed, bioRxiv) - "Treatment with Plitidepsin, a COVID-19 drug candidate, mitigates most SARS-CoV-2 pathogenic features in both the Drosophila midgut and human pulmonary cells, while modulating basal lipid droplet homeostasis in uninfected conditions. These findings establish the Drosophila midgut as a potent model for studying SARS-CoV-2 GI pathogenesis and evaluating antiviral compounds."

Journal • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Respiratory Diseases

Multidimensional Regulatory Mechanisms and Targeting Strategies of the eEF1 Family in RNA Virus Infection. (PubMed, Viruses) - "Current eEF1-targeting compounds like plitidepsin demonstrate efficacy against diverse viral families, though therapeutic development faces challenges in balancing antiviral activity with host toxicity. This review provides a theoretical foundation for developing novel antiviral strategies targeting host-virus interaction interfaces and offers insights into addressing emerging infectious diseases."

Journal • Review • Infectious Disease • EEF1A1

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 19-22 May 2025 (European Medicines Agency) - "By its judgment of 28 October 2020 in Case T-594/18, the General Court annulled the Commission Implementing Decision of 17 July 2018 refusing marketing authorisation for Aplidin. The judgment was subsequently appealed before the Court of Justice in Joined Cases C-6/21 P and C-16/21 P. On 22 June 2023, the Court of Justice set aside the judgment and referred the case back to the General Court (Case T-594/18 RENV). On 28 June 2024, the European Commission revoked the Commission Implementing Decision of 17 July 2018 refusing marketing authorisation for Aplidin. Following the adoption of this decision, the Commission has requested EMA to re-assess the application for Aplidin. EMA is currently taking the appropriate steps to implement this decision."

European regulatory • Multiple Myeloma

THALASSA: Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults with Post-COVID-19 Condition (PCC) (clinicaltrials.gov) - P2 | N=90 | Recruiting | Sponsor: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease

Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or m6A protein synthesis routes. (PubMed, Nat Commun) - "Plitidepsin is an antitumoral compound safe for treating COVID-19 that targets the translation elongation factor eEF1A...Yet, it fails to inhibit retroviruses that exploit m6A synthesis routes and are blocked by drugs targeting IGF2BP2 m6A reader. By deciphering the molecular fingerprint of cells treated with therapies targeting translation we identify a rational approach to select broad-spectrum antivirals with potential to counteract future pandemic viruses."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases • EEF1A1 • EIF2AK3 • EIF4G2 • IGF2BP2 • PERK

Leveraging Cryptic Ligand Envelopes through Enhanced Molecular Simulations. (PubMed, J Phys Chem Lett) - "We apply this approach to quantify hidden conformational heterogeneity in structurally complex ligands including the marine natural product plitidepsin. The computed conformational heterogeneity expands the small-molecule footprint beyond that typically observed in experiments, also revealing key thermodynamic and kinetic properties of single ligand-target interactions. The model agrees quantitatively with solution NMR, X-ray crystallography, and biochemical measurements, showcasing a versatile strategy to integrate receptor-bound ligand conformational ensembles in molecular design."

Journal

Didemnins as marine-derived anticancer agents: mechanistic insights and clinical potential. (PubMed, Med Oncol) - "Recent progress in developing semisynthetic derivatives, including Dehydrodidemnin B (Plitidepsin, Aplidin), have led to improved efficacy and reduced toxicity. Didemnins, especially Didemnin B, hold promise as anticancer agents. However, future research should focus on optimizing delivery methods, reducing toxicity, and exploring combination therapies to enhance their therapeutic potential in oncology."

Journal • Review • Oncology