Elosulfase alfa: First Global Approval

  title={Elosulfase alfa: First Global Approval},
  author={M. Sanford and Jin Han Lo},
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… Expand
Enzyme Replacement Therapy with Elosulfase alfa for Mucopolysaccharidosis IVA (Morquio A Syndrome): Milestones and Challenges
Although the treatment was well tolerated along all clinical trials, all patients developed antibodies against the infused enzyme, and more analyses need to be performed to reach final conclusions on the effect of immune response and elosulfase alfa treatment response. Expand
Role of elosulfase alfa in mucopolysaccharidosis IVA
The treatment was generally well tolerated, and the uncommon infusion reactions responded well to traditional enzyme replacement therapy infusion reaction management algorithms. Expand
Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y
Early intervention with elosulfase alfa is well-tolerated and produces a decrease in uKS and a trend toward improvement in growth, which is similar to that seen in untreated patients. Expand
Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome.
Long-term efficacy and safety of elosulfase alfa enzyme replacement therapy were evaluated in Morquio A patients over 96weeks in an open-label, multi-center, phase III extension study, and it was revealed that durability of 6MWT improvements was not impacted by baseline 6 MWT distance, use of a walking aid, or age. Expand
Characterization of Human Recombinant N-Acetylgalactosamine-6-Sulfate Sulfatase Produced in Pichia pastoris as Potential Enzyme for Mucopolysaccharidosis IVA Treatment.
The production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme, represents an important step in the development of a P. pastoris-based platform for production of a therapeutic GAL NS for MPS IVA enzyme replacement therapy. Expand
Therapeutic Options for Mucopolysaccharidoses: Current and Emerging Treatments
Evaluated treatments of MPS, including ERT and HSCT, and future treatments, such as gene therapy, SRT, and chaperone therapy are described, and the advantages and disadvantages are described. Expand
Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome
Long-term ERT is associated with sustained improvements in respiratory function in Morquio A syndrome; in younger patients (≤14 years), some improvement may be ascribed to growth; in older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved. Expand
Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency.
This study provides proof-of-concept for the safety and efficacy of within-patient dose escalation of olipudase alfa in patients with nonneuronopathic ASMD and minimizes the rapid production of metabolites, which can be toxic. Expand
Impact of Elosulfase Alfa on Pain in Patients with Morquio A Syndrome over 52 Weeks
Treatment with elosulfase alfa improved subjective pain score, pain locations, and pain descriptor words over 1 year (52 weeks), suggesting that elos fulfilment can reduce pain in some patients with Morquio A. Expand
Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches
In vivo and ex vivo Gene therapy (GT) strategies aimed at correcting the genetic defect in patient cells could represent a significant improvement for the treatment of MPS when compared with conventional approaches. Expand


Characterization and pharmacokinetic study of recombinant human N-acetylgalactosamine-6-sulfate sulfatase.
It is shown that the phosphorylated rhGALNS is delivered to multiple tissues, including bone, and that it functions bioactively in Galns(-/-) chondrocytes implying a potential enzyme replacement treatment. Expand
Enzyme Replacement in a Human Model of Mucopolysaccharidosis IVA In Vitro and Its Biodistribution in the Cartilage of Wild Type Mice
It is shown that enzyme replacement therapy with recombinant human GALNS results in clearance of keratan sulfate accumulation, and that such treatment ameliorates aberrant gene expression in human chondrocytes in vitro. Expand
Current and emerging management options for patients with Morquio A syndrome
The current and emerging treatment options for Morquio A syndrome are discussed, citing examples of the treatment of other mucopolysaccharidoses. Expand
The Morquio A Clinical Assessment Program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects.
The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population and indicates MPS IVA is a multisystem disorder with a continuum of clinical presentation. Expand
and Drug Administration, Center for Drug Evaluation and Research
  • Briefing Document: Vimizim (elosulfase alpha) for patients with mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome). 2013. http://www.fda.gov/downloads/ advisorycommittees/committeesmeetingmaterials/drugs/endo crinologicandmetabolicdrugsadvisorycommittee/ucm375126.pdf. Accessed 5 March
  • 2014
Vimizim (elosulfase alfa) for the treatment of mucopolysaccharidosis type IVA (Morquio syndrome): briefing document for the endocrinologic and metabolic drugs advisory committee
  • http://www.fda.gov/downloads/ advisorycommittees/committeesmeetingmaterials/drugs/endocrino logicandmetabolicdrugsadvisorycommittee/ucm375127.pdf. Accessed
  • 2013
and Drug Administration
  • FDA approves Vimizim to treat rare congenital enzyme disorder [media release].
  • 2014