Clinical UM Guideline


Subject: Elosulfase alfa (Vimizim®)
Guideline #:  CG-DRUG-55 Publish Date:    10/17/2018
Status: Reviewed Last Review Date:    09/13/2018


This document addresses the clinical indications for elosulfase alfa (Vimizim, BioMarin Inc., Novato, CA), an enzyme replacement therapy (ERT) specifically formulated for the treatment of a rare lysosomal storage disorder called mucopolysaccharidosis (MPS) Type IVA (Morquio A syndrome). Elosulfase alfa is produced in genetically engineered Chinese hamster ovary cells. The resulting recombinant therapeutic enzyme produced by this process mimics the sequence in the normal human enzyme N-acetylgalactosamine-6-sulfatase.

Clinical Indications

Medically Necessary:

Enzyme replacement therapy with elosulfase alfa is considered medically necessary for the treatment of mucopolysaccharidosis IVA (Morquio A syndrome) in individuals who meet all the following criteria:

  1. Confirmed diagnosis of Morquio A syndrome by documented reduced fibroblast or leukocyte N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity or by genetic testing; and
  2. Documented clinical signs and symptoms of Morquio A syndrome (for example, knee deformity, corneal opacity or pectus carinatum).

Not Medically Necessary:

Enzyme replacement therapy with elosulfase alfa is considered not medically necessary when the indications above are not met and for all other indications, including but not limited to, mucopolysaccharidosis IVB (Morquio B Syndrome).


The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.




Injection, elosulfase alfa, 1 mg [Vimizim]


Home infusion therapy, enzyme replacement intravenous therapy, (e.g., Imiglucerase); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem



ICD-10 Diagnosis



Morquio mucopolysaccharidoses

Discussion/General Information

Morquio A syndrome (mucopolysaccharidosis [MPS] IVA) is a very rare lysosomal storage disorder that is characterized by an autosomal recessive inheritance pattern. The disorder is caused by a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase which hampers degradation of glycosaminoglycans (GAGs) and other cellular components such as keratin sulfate (KS) and chondroitin-6-sulfate. There also exists a Morquio syndrome Type B (MPS IVB) which is less frequent in the population and generally has less severe clinical manifestations. MPS IVB is caused by deficiency of a different enzyme than MPS IVA and is therefore not amenable to treatment with elosulfase alfa.

The incidence of Morquio A syndrome is about 1/200,000 live births in the United States (US). Individuals with Morquio A appear healthy at birth, but progressively develop a wide variety of clinical manifestations caused by excessive GAG accumulation in their tissues and organs; diagnosis is complex and both the rate of disease progression and severity are variable. The most commonly seen clinical manifestations include skeletal dysplasia including dwarfism with short trunk and neck, spinal abnormalities, pectus carinatum (i.e., pigeon chest), genu valgum (i.e., knock-knee), hip dysplasia, joint hypermobility/instability, dental abnormalities, spinal cord compression and softening, breathing difficulties due to airway obstruction or restrictive pulmonary disease, cardiac valve disease, impaired vision, hearing loss and hepatosplenomegaly. Cognitive impairment is not generally associated with this disease. Individuals with a rapidly progressing phenotype generally do not survive past the age of 30 and even those with a more slowly progressing disease course rarely survive beyond their 60th year of life. Death is generally the result of cardiorespiratory or neurological complications (Hendriksz, 2015).

In 2014, the US Food and Drug Administration (FDA) approved elosulfase alfa for the treatment of Morquio A syndrome administered intravenously once weekly (Product Information [PI] Label, 2014). Elosulfase alfa is the only FDA approved disease-modifying therapy currently available for the treatment of Morquio A syndrome. FDA approval was based on two clinical trials. The first was a double-blind, randomized, placebo-controlled trial of 176 individuals with Morquio A syndrome, who were at least 5 years of age. Participants had both documented clinical symptoms of Morquio A syndrome and confirmed diagnosis by laboratory or genetic testing. At baseline, all participants could walk more than 30 meters but less than 325 meters in 6 minutes. Study participants were randomized (1:1:1) to receive either elosulfase alfa weekly, biweekly (placebo on alternating weeks to facilitate blinding), or weekly placebo. At study-end (24 weeks), individuals in the weekly treatment group walked a mean distance of 22.5 meters farther than their baseline measurement in the 6-minute walk test (6MWT; primary outcome of interest) compared to those who received placebo (95% Confidence Interval [CI], 4.0-40.9; p=0.017); no differential effect was seen in the biweekly treatment group compared to placebo. Secondary outcome measures included the 3-min stair climb test (3MSCT) and change in urine KS. While no difference was seen in the 3MSCT in those treated with elosulfase alfa, urine KS was reduced in both the weekly (-40.7%) and biweekly (-30.2%) treatment groups. The most commonly reported adverse events and serious adverse events included mild to moderate infusion associated reactions, such as vomiting, pyrexia and headache. The occurrence rate of infusion reactions were 91.5%, 94.9% and 89.7% in those treated with placebo, biweekly elosulfase alfa and weekly elosulfase alfa, respectively (Hendriksz, 2014).

In an unpublished 48-week extension trial (total of 72-week exposure), in which all but 3 participants from the original study participated in, no further improvement in walking ability was demonstrated. Approximately 8% of participants across both clinical trials had anaphylactic reactions during infusions, prompting inclusion of a boxed warning for the drug. It is also noteworthy that the safety and effectiveness of elosulfase alfa have not been established in individuals less than 5 years of age due to their exclusion from the clinical trials (PI Label, 2014).

Long-term data, 120 week follow-up, is now available and has demonstrated continued efficacy of elosulfase alfa with sustained improvement in 6MWT, 3MSCT and decreased urine KS. Pulmonary data has shown continued numerical improvement in maximum voluntary ventilation, forced vital capacity and forced expiratory volume. No new safety signals were identified (Hendriksz, 2016a, Hendriksz 2016b, Hendriksz, 2018).

In 2015, international guidelines for the management of Morquio A syndrome were published (Hendriksz, 2015). In them, the complexity of diagnosis is described in detail, and emphasis is put on laboratory, genetic and molecular methods for diagnostic confirmation. In addition, recommendations are made for endurance testing at initiation of enzyme replacement therapy and regularly for the duration of treatment as a measure of treatment efficacy. Elosulfase alfa is highly immunogenic. All participants in the initial trial who received weekly injections of elosulfase alfa developed antibodies to it. Development of these antibodies was not reportedly associated with reduced effectiveness as measured by KS excretion or incidence of anaphylaxis. The long-term effect of these antibodies on treatment efficacy or side effects was published in an extension study by Long and colleagues (2017). Following 120 weeks of treatment with elosulfase alfa, no association was demonstrated between immunogenic titers and changes in urine KS, 6MWT, or 3MSCT from baseline nor was there any association found with adverse events, including hypersensitivity reactions such as anaphylaxis.

Adverse Events and Warnings
Black box warnings from the FDA PI Label (2014) include the following information and recommendations:

Additional Information from the FDA PI Label (2014) includes:


Enzyme replacement therapy (ERT): A treatment provided, usually via intravenous infusion, to provide enzymes in an individual unable to make sufficient amounts of that enzyme on their own.

Forced vital capacity (FVC): A measurement of the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible; FVC is used assess the presence and severity of lung diseases.

25-foot walk test (T25FW): A standardized test that measures the time needed to cover 25 feet. For Morquio A patients, the test has been adapted in order to allow individuals to cover the 25 feet distance by crawling or rolling if walking is impossible.

3-min stair climb test (3MSCT): A standardized test that measures how many steps a person can ascend in 3 minutes, using rails and resting as needed.

6-minute walk test (6MWT): A standardized test that measures how far a person can walk on a hard, flat surface in 6 minutes and has been used to assess endurance in several mucopolysaccharidosis (MPS) (ATS, 2002).


Peer Reviewed Publications:

  1. Burton BK, Berger KI, Lewis GD, et al. Safety and physiological effects of two different doses of elosulfase alfa in patients with morquio a syndrome: a randomized, double-blind, pilot study. Am J Med Genet A. 2015; 167A(10):2272-2281.
  2. Hendriksz CJ, Berger KI, Giugliani R, at al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015; 167A(1):11-25.
  3. Hendriksz CJ, Berger KI, Parini R, et al. Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome. J Inherit Metab Dis. 2016a; 39(6):839-847.
  4. Hendriksz CJ, Burton B, Fleming TR, et al. Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study. J Inherit Metab Dis. 2014; 37(6):979-990.
  5. Hendriksz CJ, Parini R, AlSayed MD, et al. Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Mol Genet Metab. 2018; 123(2):127-134.
  6. Hendriksz CJ, Parini R, AlSayed MD. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome. Mol Genet Metab. 2016b; 119(1-2):131-143.
  7. Hughes D, Giugliani R, Guffon N, et al. Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa. Orphanet J Rare Dis. 2017; 12(1):98.
  8. Jones SA, Bialer M, Parini R, et al. Safety and clinical activity of elosulfase alfa in pediatric patients with Morquio A syndrome (mucopolysaccharidosis IVA) less than 5 y. Pediatr Res. 2015; 78(6):717-722.
  9. Long B, Tompkins T, Decker C, et al. Long-term Immunogenicity of Elosulfase Alfa in the Treatment of Morquio A Syndrome: Results From MOR-005, a Phase III Extension Study.  Clin Ther. 2017; 39(1):118-129.
  10. Schweighardt B, Tompkins T, Lau K, et al. Immunogenicity of elosulfase alfa, an enzyme replacement therapy in patients with Morquio A syndrome: results from MOR-004, a phase III trial. Clin Ther. 2015; 37(5):1012-1021.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American Thoracic Society (ATS). 2002. ATS Statement: Guidelines for the six-minute walk test. Available at: Accessed on August 13, 2018.
  2. Elosulfase alfa In: DrugPoints® System (electronic version). Truven Health Analytics, Greenwood Village, CO. Updated March 18, 2016. Available at: Accessed on August 13, 2018.
  3. Elosulfase alfa Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised June 02, 2016. Accessed on August 13, 2018.
  4. Hendriksz CJ, Berger KI, Giugliani R, at al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015; 167A(1):11-25.
  5. Vimizim [Product Information]. BioMarin Inc., Novato, CA.; February 14, 2014. Available at: Accessed on August 13, 2018.
Websites for Additional Information
  1. MedlinePlus. Morquio syndrome. Updated August 02, 2018. Available at: Accessed on August 13, 2018.
  2. National Organization for Rare Diseases. Lysosomal Storage Disorders. Available at: Accessed on August 13, 2018. 


The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.







Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion/General Information, References and Websites sections.



MPTAC review. Updated Description, General/Information and References section. Updated header language from “Current Effective Date” to “Publish Date.”



MPTAC review. Initial document development.