RESUMEN
Imlifidase (IdefirixTM), a cysteine protease derived from the immunoglobulin G (IgG)degrading enzyme of Streptococcus (S.) pyogenes is being developed by Hansa Biopharma AB for treatment of transplant rejection and rare IgG-mediated autoimmune conditions. In August 2020, intravenous imlifidase received its first global approval in the EU for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor. Imlifidase is currently undergoing clinical evaluation for the prevention of kidney transplant rejection in the USA, Australia, France and Austria, and clinical development is underway for anti-glomerular basement membrane disease, and for Guillain-Barre syndrome in France, the UK and the Netherlands. This article summarizes the milestones in the development of imlifidase leading to this first approval for desensitization treatment of highly sensitized adult kidney transplant patients with positive crossmatch against an available deceased donor.
Asunto(s)
Enfermedad por Anticuerpos Antimembrana Basal Glomerular/tratamiento farmacológico , Proteínas Bacterianas/uso terapéutico , Aprobación de Drogas , Rechazo de Injerto/tratamiento farmacológico , Síndrome de Guillain-Barré/tratamiento farmacológico , Administración Intravenosa , Animales , Enfermedad por Anticuerpos Antimembrana Basal Glomerular/inmunología , Proteínas Bacterianas/farmacología , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Desensibilización Inmunológica/métodos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Unión Europea , Síndrome de Guillain-Barré/inmunología , Antígenos HLA/inmunología , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Raras/tratamiento farmacológico , Enfermedades Raras/inmunologíaRESUMEN
Lenvatinib (Lenvima®) is an oral small molecule inhibitor of multiple receptor tyrosine kinases, and is approved for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) in the USA, EU, Japan and China. The approval of lenvatinib was based on results of the randomized, open-label, multinational, non-inferiority phase III REFLECT trial in patients with unresectable HCC, who had not received treatment for advanced disease. In REFLECT, lenvatinib was non-inferior, but not superior, to sorafenib (current standard of care) for overall survival (OS). However, lenvatinib was associated with significant improvements compared with sorafenib in terms of all secondary endpoints [higher objective response rate (ORR), and longer progression-free survival (PFS) and time to progression (TTP)]. Lenvatinib had a generally manageable tolerability profile in REFLECT, with the most common treatment-emergent adverse events being hypertension, diarrhoea, decreased appetite and decreased weight. Given its non-inferior efficacy to sorafenib and manageable tolerability profile, lenvatinib represents a long-awaited alternative option to sorafenib for the first-line systemic treatment of patients with unresectable HCC. Further clinical experience may be required to fully define the position of lenvatinib in this setting.