Effective Date

Date of Origin 

01-01-2025            

VOXZOGO®

(vosoritide)

Subcutaneous injection

Indicated to increase linear growth in pediatric patients with achondroplasia with open epiphyses.

This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

1

Achondroplasia

Achondroplasia is the most commonly occurring abnormality of bone growth (skeletal dysplasia), occurring in approximately 1 in 15,000-35,000 live births and affects both males and females equally. This genetic disorder is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Fibroblast growth factor receptors (FGFRs) belong to the tyrosine kinase family and regulate various biological processes including cell proliferation and differentiation during development, as well as tissue repair.

Achondroplasia occurs as a result of a spontaneous genetic mutation in approximately 80 percent of patients. In the remaining 20 percent of cases, it is inherited from either parent and follows an autosomal dominant pattern of inheritance. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy.(3) Like some other severe growth disorders, it is also associated with potentially serious medical complications such as foramen magnum and spinal stenosis, both of which cause increased morbidity and mortality.(2) This genetic disorder is characterized by an unusually large head (macrocephaly), short upper arms (rhizomelic dwarfism), and short stature (adult height of approximately 4 feet). Achondroplasia does not typically cause impairment or deficiencies in mental abilities. If the bones that join the head and neck do not compress the brainstem or upper spinal cord (craniocervical junction compression), life expectancy is near normal.(3)

Growth hormone treatment has been found to be ineffective in patients with deformities of the lower limbs and to date, it has not been confirmed whether the administration of somatropin negatively affects the severity of foramen narrowing and pressure on the spinal cord, and no symptoms of acromegaly have been observed in the treated patients. A meta-analysis of recombinant human growth hormone treatment in achondroplasia based on an extensive group of patients shows that data about body disproportion in GH treatment are ambiguous.(5)

Efficacy

VOXZOGO is a recombinant C-type natriuretic peptide analog that stimulates endochondral ossification, a process that is inhibited in patients with achondroplasia patients.(1)

The safety and effectiveness of VOXZOGO in 121 genetically confirmed patients with achondroplasia were assessed in one 52-week, multi-center, randomized, double-blind, placebo-controlled, phase 3 study - Study 1 (NCT03197766). The dosage of VOXZOGO was 15 mcg/kg administered subcutaneously once daily. Baseline standing height, weight Z-score, body mass index (BMI) Z-score, and upper to lower body ratio were collected for at least 6 months prior to randomization. Subjects with limb-lengthening surgery in the prior 18 months or who planned to have limb-lengthening surgery during the study period were excluded and patients must have been ambulatory and able to stand to participate.(6) The study included a 52-week placebo-controlled treatment phase followed by an open-label treatment extension study period in which all subjects received Voxzogo. The primary efficacy endpoint was the change from baseline in annualized growth velocity (AGV) at Week 52 compared with placebo. The subjects’ ages ranged from 5.1 to 14.9 years with a mean of 8.7 years. Sixty four (53%) subjects were male and 57 (47%) were female. Overall, 86 (71%) subjects were White, 23 (19%) were Asian, 5 (4%) were Black or African American, and 7 (6%) were classified as “multiple” race.(1)

In children randomized to vosoritide, annualized growth velocity increased from 4.26 cm/year at baseline to 5.39 cm/year at 52 weeks and 5.52 cm/year at week 104. In children who crossed over from placebo to vosoritide in the extension study, annualized growth velocity increased from 3.81 cm/year at week 52 to 5.43 cm/year at week 104. No new adverse effects of vosoritide were detected. Longer-term studies are needed to determine whether vosoritide affects pubertal growth velocity, body segment proportionality, final adult height, or complications associated with achondroplasia. Overall, vosoritide treatment has safe and persistent growth-promoting effects in children with achondroplasia, and offers a precision therapy for patients impacted by this condition.(7)

Safety

VOXZOGO does not have any contraindications.(1)

1

VOXZOGO Prescribing Information. BioMarin Pharmaceutical Inc. November 2021.

2

Hogler, W., Ward, LM. New developments in the management of achondroplasia. Wien Med Wochenschr 170, 104–111 (2020). https://doi.org/10.1007/s10354-020-00741-6

3

Achondroplasia. NORD. https://rarediseases.org/rare-diseases/achondroplasia

4

Kubota T, Adachi M, Kitaoka T, et al. Clinical Practice Guidelines for Achondroplasia. Clin Pediatr Endocrinol. 2020;29(1):25-42. doi:10.1297/cpe.29.25

5

Wrobel W, Pach E, Ben-Skowronek I. Advantages and Disadvantages of Different Treatment Methods in Achondroplasia: A Review. International Journal of Molecular Sciences. 2021; 22(11):5573. https://doi.org/10.3390/ijms22115573

6

A Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia. BioMarin Pharmaceutical. Available at: https://clinicaltrials.gov/ct2/show/NCT03197766

7

Savarirayan R, Tofts L, Irving M, et al. Safe and persistent growth-promoting effects of vosoritide in children with achondroplasia: 2-year results from an open-label, phase 3 extension study. Genet Med. 2021;23(12):2443-2447. doi:10.1038/s41436-021-01287-7.

Voxzogo

vosoritide for subcutaneous inj

0.4 MG ; 0.56 MG ; 1.2 MG

M ; N ; O ; Y

N

Voxzogo

vosoritide for subcutaneous inj

0.4 MG ; 0.56 MG ; 1.2 MG

30

Vials

30

DAYS

Voxzogo

vosoritide for subcutaneous inj

0.4 MG ; 0.56 MG ; 1.2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Voxzogo

vosoritide for subcutaneous inj

0.4 MG ; 0.56 MG ; 1.2 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. ALL of the following:
      1. The patient has a diagnosis of achondroplasia as confirmed by ONE of the following (medical records required):
         1. Genetic testing OR
         2. Radiographic findings AND
      2. The requested agent will be used to increase linear growth AND
      3. The patient has open epiphyses OR
   2. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient will NOT be using the requested agent in combination with another growth hormone agent for the requested indication AND
5. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has open epiphyses AND
3. The patient has had clinical benefit with the requested agent AND
4. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., endocrinologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
5. The patient will NOT be using the requested agent in combination with another growth hormone agent for the requested indication AND
6. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity (dose) exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval:  12 months