Elosulfase alfa: First Global Approval

Abstract

Elosulfase alfa (Vimizim™) is a recombinant form of N-acetylgalactosamine-6-sulfatase (GALNS) that was developed by BioMarin Pharmaceutical Inc. as an enzyme replacement therapy for patients with mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome. Patients with MPS IVA have a GALNS deficiency, which results in serious musculoskeletal, cardiorespiratory and other system disturbances. Elosulfase alfa was approved by the US FDA on 14 February 2014 for the treatment of MPS IVA. The European Medicines Agency Committee for Medicinal Products for Human Use (CHMP) has recently recommended that elosulfase alfa be approved for use in the EU in the same indication. Within the last year, the manufacturer has also filed applications for approval for the use of elosulfase alfa in MPS IVA in Brazil, Australia, Canada and Mexico. This article summarizes the milestones in the development of elosulfase alfa leading to its first global approval in MPS IVA.

Evidence, illness, and causation: An epidemiological perspective on the Russo–Williamson Thesis

“…Tasimelteon (for treatment of sleep-wake disorder in blind individuals) was discovered as a novel agonist of human melatonin 1a and 1b receptors (Vachharajani, Yeleswaram et al 2003). Elosulfase alfa (for treatment of Morquio A syndrome, an inherited metabolic disorder) is a form of the human enzyme N-acetylgalactosamine-6-sulfatase (the enzyme that is deficient in individuals with Morquio A syndrome) that is manufactured through recombinant DNA technology (Sanford and Lo 2014). For all three of these interventions, existing evidence about the mechanisms of disease suggested the mechanism of a hypothetical drug, and this mechanistic reasoning drove the development of the drug before any exposure-outcome evidence could be collected.…”

Enfermedad de Morquio (mucopolisacaridosis IV-A): aspectos clínicos, diagnósticos y nuevo tratamiento con terapia de reemplazo enzimático

“…26 El 14 de febrero de 2014, la FDA aprobó la primera terapia recombinante para MPS IV-A (elosulfasa alfa -Vimizym ® -), y, el 20 de febrero, la Agencia de Medicina Europea recomendó su aprobación para la misma indicación. 27 La elosulfasa alfa tiene adherida una cadena de oligosacárido terminal (manosa-6-fosfato), por la cual es reconocida e internalizada por las células luego de su infusión intravenosa. Una vez internalizada, la actividad enzimática específica se incrementa en forma dosis-dependiente y se logra el catabolismo del queratán y condroitín sulfato.…”

“…Finalmente, 8 de 10 puntos terciarios fueron favorables para el grupo A con respecto al grupo placebo. 27,28 Los efectos adversos descritos con mayor frecuencia fueron escalofríos, cefaleas, náuseas y fatiga. Ningún paciente debió ser retirado de la fase 3 y los pocos eventos adversos serios reportados fueron relacionados con las complicaciones conocidas de la MPS IV-A.…”

Modern Approaches to Therapy for Children With Mucopolysaccharidosis

“…Существенной динамики суставно-го статуса (тугоподвижность суставов и контрактуры) на фоне терапии обнаружено не было, что связано, по-видимому, со стабилизацией процесса изменения суставов в структуре МПС. Не получено достоверных Для МПС типа IV в 2014 г. разработан и зарегистрирован пре-парат, представляющий собой рекомбинантную форму N-ацетилгалактозамин-6-сульфатазы, доступный в насто-ящее время только за границей [28].…”