Drug Trials Snapshots: VOXZOGO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the VOXZOGO Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
VOXZOGO (vosoritide)
(vox zoe’ goe )
Biomarin Pharmaceutical Inc.
Approval date: November 20, 2021
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
VOXZOGO is a drug to improve growth in children with achondroplasia who are 5 years of age and older and still have the potential to grow.
Achondroplasia is a genetic disorder in which bone does not form properly. The condition is characterized by short arms and legs, ear infections and other problems related to the abnormal bone development.
How is this drug used?
VOXZOGO is an injection given under the skin (subcutaneously) once daily.
Who participated in the clinical trials?
The FDA approved VOXZOGO based on evidence from a Phase 3 clinical trial (NCT03197766) in 121 subjects with achondroplasia. The trial was conducted at 24 sites in 7 countries: United States, Australia, Spain, United Kingdom, Germany, Japan, and Turkey. The same trial was used to assess efficacy and safety.
What are the benefits of this drug?
In a clinical trial, VOXZOGO increased annualized growth velocity (AGV), or the rate of growth over one year, compared to subjects who received placebo (Table 1). Another trial is ongoing to assess whether VOXZOGO improves final adult height.
What are the benefits of this drug (results of trials used to assess efficacy)?
The results of the primary efficacy endpoint, or the rate of growth over one year, are presented in Table 1.
Table 1 Effects of VOXOGO on Annualized Growth Velocity (cm/year) at Week 52
| Mean Change from Baseline | ||
|---|---|---|
| VOXOGO (N=60) | Placebo (N=61) | Difference (95% Confidence interval) |
| 1.40 | -0.17 | 1.57 (1.22, 1.93) |
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: VOXZOGO worked similarly in males and females.
- Race: VOXZOGO worked similarly in Whites and Asians. The number of subjects of other races was limited; differences in how VOXZOGO worked among other races could not be determined.
- Age: VOXZOGO worked similarly in subjects across age groups in the trial (≥5 to <8 years of age, ≥8 to <11 years of age and ≥11 to <15 years of age).
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 2 shows how the drug worked among the different sex, race, and age groups.
Table 2 Effects of VOXZOGO on Annualized Growth Velocity (cm/year) at Week 52, by Sex, Race, and Age Subgroups
| Subgroups (n[V], n[P]) |
Mean Change from Baseline | Difference a (95% CI) |
|
|---|---|---|---|
| VOXZOGO N=60 |
Placebo N=61 |
||
| Sex | |||
| Boys (31, 33) | 1.33 | -0.03 | 1.46 (1.02, 1.90) |
| Girls (29, 28) | 1.47 | -0.32 | 1.66 (1.20, 2.12) |
| Race | |||
| White (45, 41) | 1.38 | -0.23 | 1.59 (1.22, 1.97) |
| Asian (10, 13) | 1.41 | -0.07 | 1.56 (1.05, 2.07) |
| Age Group (years) | |||
| ≥5 to <8 (31, 24) | 1.43 | 0.10 | 1.42 (0.93, 1.90) |
| ≥8 to <11 (17, 24) | 1.80 | -0.47 | 1.99 (1.32, 2.67) |
| ≥11 to <15 (12, 13) | 0.88 | -0.20 | 1.32 (0.60, 2.03) |
Abbreviations: N, total number of subjects in the group; n, total number of subjects in the subgroup; V, Voxzogo; P, placebo.
a. Treatment differences and credible intervals (CI) may not match value of (VOXOGO - Placebo) since estimates include relevancy of outcomes from other subgroups.
What are the possible side effects?
The most common side effects of VOXZOGO include injection site reactions, vomiting and decreased blood pressure.
What are the possible side effects (results of trials used to assess safety)?
Table 3 shows the frequency of side effects occurring in ≥5% of subjects treated with VOXZOGO and more frequently than subjects who received placebo.
Table 3. Adverse Reactions that Occurred in ≥5% of Subjects Treated with VOXZOGO and at a Rate Greater than Placebo# (52 Weeks of Treatment)
| Adverse Reaction | Placebo (N=61) n (%) |
VOXZOGO (N=60) n (%) |
|---|---|---|
| Injection site erythema* | 42 (69%) | 45 (75%) |
| Injection site swelling* | 22 (36%) | 37 (62%) |
| Vomiting | 12 (20%) | 16 (27%) |
| Injection site urticaria* | 6 (10%) | 15 (25%) |
| Arthralgia | 4 (7%) | 9 (15%) |
| Decreased blood pressure | 3 (5%) | 8 (13%) |
| Gastroenteritisa | 5 (8%) | 8 (13%) |
| Diarrhea | 2 (3%) | 6 (10%) |
| Dizzinessb | 2 (3%) | 6 (10%) |
| Ear pain | 3 (5%) | 6 (10%) |
| Influenza | 3 (5%) | 6 (10%) |
| Fatiguec | 2 (3%) | 5 (8%) |
| Seasonal allergy | 1 (2%) | (7%) |
| Dry skin | 0 | 3 (5%) |
Abbreviations: N, total number of subjects in the group; n, number of subjects with the side effect; %, percent of subjects with the side effect
#Include adverse reactions occurring more frequently in the vosoritide arm and with a risk difference of ≥ 5% (i.e., difference of >2 subjects) between treatment arms
*Injection site reactions symptoms occurring more frequently in VOXZOGO - treated subjects than placebo
a Includes the preferred terms: gastroenteritis and gastroenteritis, viral
b Includes the preferred terms: dizziness, presyncope, procedural dizziness, vertigo
c Includes the preferred terms: fatigue, lethargy, malaise
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of overall side effects was overall similar in males and females. Given the small number of subjects in each group, results must be interpreted with caution.
- Race: The number of patients of races other than White was small; therefore, differences in side effects among races could not be determined.
- Age: The occurrence of overall side effects was similar across age groups in the trial (≥5 to <8 years of age, ≥8 to <11 years of age and ≥11 to <15 years of age). Given the small number of subjects in each group, results must be interpreted with caution.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 4. Adverse Reactions by Sex
| Preferred Term | VOXZOGO Male N=31 n (%) |
VOXZOGO Female N=29 n (%) |
Placebo Male N=33 n(%) |
Placebo Female N=28 n (%) |
|---|---|---|---|---|
| Any adverse reaction | 30 (97) | 29 (100) | 32(97) | 28 (100) |
| Injection site erythema | 23 (74) | 22 (76) | 25 (76) | 17 (61) |
| Injection site swelling | 19 (61) | 18 (62) | 14 (42) | 8 (29) |
| Vomiting | 5 (16) | 12 (41) | 9 (27) | 3 (11) |
| Injection site urticaria | 9 (29) | 6 (21) | 5 (15) | 1 (4) |
| Arthralgia | 5 (16) | 4 (14) | 1 (3) | 3 (11) |
| Blood pressure decreased | 5 (16) | 2 (7) | 1 (3) | 2 (7) |
Abbreviations: N, total number of subjects in the group; n, number of subjects with the side effect; %, percent of subjects with the side effect
Table 5. Adverse Reactions by Age Groups
| Preferred Term | VOXZOGO ≥5 to <8 N=31 n (%) |
VOXZOGO ≥8 to <11 N=17 n (%) |
VOXZOGO ≥11 to <15 N=12 n (%) |
Placebo ≥5 to <8 N=24 n (%) |
Placebo ≥8 to <11 N=24 n (%) |
Placebo ≥11 to <15 N=13 n (%) |
|---|---|---|---|---|---|---|
| Any adverse reaction | 30 (97) | 17 (100) | 12 (100) | 24 (100) | 24 (100) | 12 (92) |
| Injection site erythema | 26 (84) | 12 (71) | 7 (58) | 16 (67) | 17 (71) | 9 (69) |
| Injection site swelling | 23 (74) | 10 (59) | 4 (33) | 9 (37) | 9 (37) | 4 (31) |
| Vomiting | 11 (35) | 4 (23) | 2 (17) | 4 (17) | 6 (25) | 2 (15) |
| Injection site urticaria | 7 (23) | 4 (23) | 4 (33) | 1 (4) | 4 (17) | 1 (8) |
| Arthralgia | 2 (6) | 3 (18) | 4 (33) | 0 | 2 (8) | 2 (15) |
| Blood pressure decreased | 4 (13) | 2 (12) | 1 (8) | 1 (4) | 1 (4) | 1 (8) |
Abbreviations: N, total number of subjects in the group; n, number of subjects with the side effect; %, percent of subjects with the side effect
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the clinical trial.
Figure 1. Baseline Demographics by Sex
Figure 2 summarizes the percentage of subjects by race in the clinical trial.
Figure 2. Baseline Demographics by Race
Figure 3 summarizes the percentage of subjects by age in the clinical trial.
Figure 3. Baseline Demographics by Age
Figure 4 summarizes the percentage of subjects by ethnicity in the clinical trial.
Figure 4. Baseline Demographics by Ethnicity
Who participated in the trials?
The table below summarizes demographics of subjects in the clinical trial.
Table 6 Baseline Demographics
| Treatment Group | Total (N=121) |
|||||
|---|---|---|---|---|---|---|
| VOXZOGO (N=60) |
Placebo (N=61) |
|||||
| Sex | ||||||
| Female | 29 | 23.9% | 28 | 23.1% | 57 | 47.1% |
| Male | 31 | 25.6% | 33 | 27.2% | 64 | 52.8% |
| Race | ||||||
| White | 45 | 37.1% | 41 | 33.8% | 86 | 71.0% |
| Asian | 10 | 8.2% | 13 | 10.7% | 23 | 19.0% |
| Black or African American | 3 | 2.4% | 2 | 1.6% | 5 | 4.1% |
| Multiple | 2 | 1.6% | 5 | 4.1% | 7 | 5.7% |
| Age Group (years) | ||||||
| >= 5 to < 8 | 31 | 25.6% | 24 | 19.8% | 55 | 45.4% |
| >= 8 to < 11 | 17 | 14.0% | 24 | 19.8% | 41 | 33.8% |
| >= 11 to < 15 | 12 | 9.9% | 13 | 10.7% | 25 | 20.6% |
| Ethnicity | ||||||
| Hispanic or Latino | 1 | 8% | 6 | 4.9% | 7 | 5.7% |
| Not Hispanic or Latino | 59 | 48.7% | 55 | 45.4% | 114 | 94.2% |
| Country | ||||||
| United States | 27 | 22.3% | 26 | 21.4% | 53 | 43.8% |
| Australia | 11 | 9.0% | 11 | 9.0% | 22 | 18.1% |
| Spain | 5 | 4.1% | 8 | 6.6% | 13 | 10.7% |
| United Kingdom | 8 | 6.6% | 5 | 4.1% | 13 | 10.7% |
| Germany | 5 | 4.1% | 5 | 4.1% | 10 | 8.2% |
| Japan | 3 | 2.4% | 4 | 3.3% | 7 | 5.7% |
| Turkey | 1 | 8.0% | 2 | 1.6% | 3 | 2.4% |
How were the trials designed?
The benefits and side effects of VOXZOGO were evaluated in a multinational clinical trial.
Pediatric subjects 5 to 14 years old with achondroplasia were assigned at random to daily injections of VOXZOGO or placebo for 52 weeks. Neither the subject nor the healthcare providers knew what medication was being given.
The benefit of VOXZOGO in comparison to placebo was assessed by mean change in annual growth velocity (change in standing height over 1 year) and comparing it to the placebo group.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.