Featured, In the News / Politics:

FDA Approves Drug Elosulfase Alfa (Vimizim™) for Mucopolysaccharidosis (MPS IVA)

By: Erica Dimitropoulos Co-Copy Editor [Content- Focused]


On February 14, 2014, elosulfase alfa (Vimizim) became an FDA-approved enzyme replacement therapy for Morquio A Syndrome, a type of mucopolysaccharidosis (MPS IVA).1 Elosulfase alfa was granted priority review and was also the first drug to receive the Rare Pediatric Disease Priority Review Voucher that motivates the development of new drugs for the treatment of rare pediatric diseases.1

Mucopolysaccharidosis type IV is an autosomal recessive disease that affects approximately 1 in every 200,000 individuals and typically appears within the first three years of life.2, 3 Early physical signs often manifest as kyphoscoliosis (abnormal curvature of the spine), genu valgum (knock-knee), and pectus carinatum (pigeon chest).2 Generally, diagnosis is made by physical and ophthalmologic examinations, skeletal radiographs, and urine glycosaminoglycan (GAG) analysis. Confirmation of suspected disease is provided by genetic assay.2 Prognosis upon diagnosis is contingent upon severity, as those with milder forms can live into adulthood, while more severe cases may terminate in adolescence.3 The average lifespan of patients living with MPS IV is 40 years.4

Mucopolysaccharidosis is a storage disorder caused by the deficiency of lysosomal enzymes.4 There are many different types of mucopolysaccharidosis and there are two subtypes of MPS IV: Type A and Type B. One cannot determine the type of MPS IV based on symptomatology. Type A is caused by a mutation in the N-acetylgalactosamine-6- sulfatase (GALNS) gene, and type B by that of the beta-galactosidase (GLB1)gene. These genes are both responsible for the coding of enzymes that break down glycosaminoglycans (GAGs), originally referred to as mucopolysaccharides.3 Without the necessary enzymes coded by these genes, GAG substrates, namely keratan sulfate (KS) and chrondroitin-6-sulfate (C6S), accumulate in the lysosomes of cells of tissues and organs, especially bones, and cause damage.5, 6

Patients with MPS IV often experience abnormalities of the ribs, chest, spine, hips, and wrists.3 Some joints may be restricted, while others may be overly flexible or hypermobile. Stunted growth, dwarfism, bone deformities, and gait abnormalities are all part of this disease process.As a result, movement becomes very difficult and patients are frequently confined to a wheelchair as early as their teens.6 Furthermore, the odontoid process can be underdeveloped and cause improper alignment of cervical vertebrae, compression of the spinal cord, paralysis, or even death.3 Other complications include vision loss due to clouding of the cornea, frequent ear and upper respiratory infections, hearing loss, thinning tooth enamel, abnormalities of the heart, and hepatomegaly.3, 6

Elcosulfase alfa (Vimizim) replaces the missing GALNS gene in patients with MPS IVA. When the mannose-6-phosphate-terminated oligosaccharide chains of elosulfase alfa bind to mannose-6-phosphate receptors, the drug is taken up into the lysosomes of the cell where it can perform its catabolic actions, namely the breakdown of GAGs KS and C6S.4-6

Elcosulfase alfa is an intravenous infusion dosed at 2 mg/kg and infused over 3.5 to 4.5 hours once weekly.5 It is a purified human enzyme formulated via recombinant DNA technology in a Chinese hamster ovary cell line.5 As a result, anaphylaxis and hypersensitivity reactions can occur. Patients with febrile or respiratory illnesses may be at a higher risk of developing these reactions and must therefore be evaluated prior to administration.5 Also, because sleep apnea is common among patients with MPS IVA, evaluation of airway patency should be performed before initiating the infusion. The use of oxygen supplementation or continuous positive airway pressure in patients with sleep apnea should be noted so that these treatments may be available during the infusion if needed.5 The last warning and precaution associated with this medication addresses those with spinal or cervical cord compression. Spinal or cervical cord compression is a serious complication of MPS IV, and patients must be monitored for signs and symptoms such as back pain, urinary and fecal incontinence, and paralysis. However, these complications can occur as a natural progression of MPS IV, and were seen in patients on elcosulfase alfa and patients taking placebo.5 Other common and less serious side effects include nausea and vomiting, headache, pyrexia and chills, abdominal pain, and fatigue.5, 6 To attenuate the possibility of hypersensitivity reactions and side effects, pretreatment with an antihistamine with or without an antipyretic is recommended.5

The safety and efficacy of elcosulfase alfa were assessed over 24 weeks in a randomized, double-blind, placebo-controlled trial of 176 patients living with MPS IVA.7 Efficacy was shown using a primary endpoint of change in six-minute walking distance after 24 weeks. Patients receiving elcosulfase alfawere able to walk an average of 22.5 meters longer during that time compared to patients on placebo, a statistically significant difference.7 While this translates into improved symptomatology, it does not yet say anything regarding long term prognosis, effect on skeletal and non-skeletal features, or anticipated life-span.2 Also, statistical significance was not reached in other parameters such as three minute stair climb, measures of respiratory function, or results of a health assessment questionnaire.6 Further trials and extension studies based on different patient populations are currently in progress.6

Prior to the approval of elcosulfase alfa (Vimizim), no treatment options existed for patients living with MPS IVA.7 Supportive care was the mainstay of therapy, including nonsteroidal anti-inflammatory drugs (NSAIDs) for joint pain, antibiotics for pulmonary infections, and oxygen supplementations when necessary.4 Surgical interventions were also often required to aid patient’s mobility and improve quality of life.4 As said by Jean-Jacques Bienaime, Chief Executive Officer of the developers of Vimizim, Biomarin, “Vimizim is the first and only therapy designed to address the condition [MPS IVA] at the cellular level, fulfilling a large unmet medical need for patients and their families.” 7 While no true cure yet exists, many patients and healthcare providers are hopeful that this drug may open doors to the development of treatments for other types of mucopolysaccharidosis and similar orphan diseases.


  1. Fisher, A. FDA approves Vimizim to treat rare congenital enzyme disorder. US Food and Drug Administration. February 11, 2014 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm386008.htm. Accessed April 4, 2014.
  2. Regier DS, Oetgen M, Tanpaiboon P. Mucopolysaccharidosis Type IVA. GeneReviews[Internet]. March 13, 2014  http://www.ncbi.nlm.nih.gov.jerome.stjohns.edu:81/books/NBK148668/. Accessed April 12, 2014.
  3. Mucopolysaccharidosis Type IV. Genetics Home Reference. April 17, 2014. http://ghr.nlm.nih.gov/condition/mucopolysaccharidosis-type-iv. Accessed April 19, 2014.
  4. Endocrinologic and metabolic Drugs Advisory Committee. Vimizim for the treatment of Mucopolysaccharidosis Type IVA (Morquio A Syndrome). Biomarin. November 19, 2013. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM375127.pdf. Accessed April 4, 2014.
  5. VIMIZIM [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2014.
  6. Sanford, M. Elosulfase alfa: First Global Approval. Adis R&D, Insight. April 4, 2014. http://download.springer.com.jerome.stjohns.edu:81/static/pdf/845/art%253A10.1007%252Fs40265-014-0210-z.pdf?auth66=1398204573_54501039a9d86929c437ff11d59c104c&ext=.pdf. Accessed April 19, 2014.
  7. McCarty, T. BioMarin Announces FDA Approval for VIMIZIM™ (elosulfase alfa) for the Treatment of Patients With Morquio A Syndrome. Biomarin. February 14, 2014. http://investors.bmrn.com/releasedetail.cfm?ReleaseID=825970) Accessed April 19, 2014.

[pubmed_related keyword1=”elosulfase” keyword2=”mucopolysaccharidosis” keyword3=”mps”]

Published by Rho Chi Post
Both comments and trackbacks are currently closed.