What Is Vosoritide?
Vosoritide, also known by the brand name VOXZOGO®, is an FDA-approved medication for Achondroplasia. It is a modified recombinant human C-type natriuretic peptide (CNP). CNP is a natural signaling molecule that helps regulate bone growth by promoting the elongation of bones. Vosoritide works by mimicking the action of natural CNP, which can help to improve linear growth in individuals with certain genetic conditions that affect bone development.
Beyond its approved use, vosoritide is actively being studied in clinical trials for a range of other conditions characterized by short stature or impaired growth. These investigational uses include Hypochondroplasia, Short Stature, Mucopolysaccharidosis type VI (MPS VI), Noonan Syndrome, Turner Syndrome, Idiopathic Short Stature, and Mucopolysaccharidosis type IVA (MPS IVA). The drug is typically administered as a subcutaneous injection.
Uses and Conditions Under Study
Vosoritide is primarily studied for conditions that cause short stature or affect bone growth. The most prominent group of conditions under investigation are those leading to various forms of short stature. Achondroplasia, for which vosoritide is approved, is a genetic disorder that results in disproportionately short stature. Vosoritide is thought to help by promoting bone growth. Two trials are investigating vosoritide for this condition.
Other related conditions include Hypochondroplasia, another genetic disorder causing short stature, which is being studied in 3 trials. General Short Stature is the focus of 2 trials, and Idiopathic Short Stature, where the cause is unknown, is being explored in 1 trial. Vosoritide is also being investigated for short stature associated with specific genetic syndromes: Noonan Syndrome (1 trial) and Turner Syndrome (1 trial). Turner syndrome is characterized by a missing sex chromosome in females, leading to short stature, and vosoritide may offer a new therapeutic option.
Additionally, vosoritide is being studied for certain mucopolysaccharidosis (MPS) types. These are rare genetic disorders that cause various symptoms, including skeletal abnormalities. MPS VI is being investigated in 1 trial, and MPS IVA is also being studied in 1 trial. These studies aim to understand if vosoritide can help manage the skeletal manifestations of these complex conditions.
Dosing
Vosoritide is administered as an injection. It is supplied as a lyophilized powder that requires reconstitution before use, typically prepared for subcutaneous injection using a vial and syringe. The dosing regimen for vosoritide is based on the participant's weight, following a specific weight-band dosing schedule.
Clinical trials have explored different investigational doses and regimens. These include studies of a Low Dose, Medium Dose, and High Dose of vosoritide. While some trials have investigated weekly subcutaneous injections, other studies have explored a once-daily subcutaneous injection regimen. For conditions like Achondroplasia, the approved dosing follows a weight-band regimen.
Vosoritide has been studied in pediatric patients, particularly for conditions like Achondroplasia and Mucopolysaccharidosis types IVA and VI, where the dose is carefully determined by weight. The investigational product BMN 333 at a selected dose after Phase 2 has also been part of studies, alongside comparisons to Human Growth Hormone and Standard of Care Alone in some trial arms.
Side Effects
The most common side effect reported with Vosoritide was injection site reactions, occurring in 85% of patients compared to 7% of those on placebo. Other frequently observed side effects included:
- Vomiting: 57% of patients taking Vosoritide experienced vomiting, compared to 26% on placebo.
- Headache: 46% of patients taking Vosoritide experienced headache, compared to 29% on placebo.
- Nausea: 33% of patients taking Vosoritide experienced nausea, compared to 15% on placebo.
- Hypotension (low blood pressure): 18% of patients taking Vosoritide experienced hypotension, compared to 2% on placebo.
- Dizziness: 16% of patients taking Vosoritide experienced dizziness, compared to 5% on placebo.
- Fatigue: 15% of patients taking Vosoritide experienced fatigue, compared to 7% on placebo.
Other side effects observed in clinical trials, for which a placebo comparison was not provided, included hypophosphatemia (low phosphate levels) in 11% of patients, syncope (fainting) in 7%, bradycardia (slow heart rate) in 5%, and angioedema (swelling under the skin) in 1% of patients.
Clinical Trial Results
Achondroplasia in Children
The effectiveness of Vosoritide was evaluated in children with achondroplasia in a randomized, double-blind, placebo-controlled study (Study 106-201, NCT03424018). This trial included 121 children aged 5 to 18 years. After 52 weeks, the primary goal was to measure the change in annualized growth velocity (AGV).
Patients treated with Vosoritide showed a mean increase in AGV of 1.6 cm/year from baseline, while those on placebo had a mean increase of 0.1 cm/year. This resulted in a statistically significant difference of 1.5 cm/year in favor of Vosoritide. Furthermore, 61% of patients receiving Vosoritide experienced an increase in AGV of 1.0 cm/year or more, compared to only 10% of patients on placebo. Vosoritide also led to improvements in body proportionality, such as reductions in the upper-to-lower body segment ratio and the sitting height-to-standing height ratio, indicating more balanced growth.
A long-term, open-label extension study (Study 106-901, NCT02055157) further assessed Vosoritide in 35 children aged 0 to 5 years with achondroplasia. After 2 years of treatment, these children showed a mean increase in AGV of 2.1 cm/year. This beneficial effect on growth was sustained over time, with a mean increase in AGV of 1.7 cm/year observed after 5 years of continuous treatment. Improvements in body proportionality, similar to those seen in the shorter-term study, were also maintained over the 5-year period, suggesting sustained positive effects on overall growth and development.
Currently Recruiting Trials
Vosoritide is currently being investigated in several clinical trials for various conditions related to growth. These studies aim to understand how vosoritide works, its safety, and its effectiveness in different patient populations. Participating in a clinical trial can help advance medical knowledge and potentially offer new treatment options.
One ongoing study, NCT07441876, is a seamless Phase 2/3 trial comparing BMN 333 against vosoritide in children with achondroplasia who have not received prior treatment. This study aims to enroll 160 pediatric participants to evaluate the safety and effectiveness of both treatments.
Another trial, NCT07126262, is a Phase 2 study investigating vosoritide in children with hypochondroplasia, specifically those aged 0 to less than 36 months. This study seeks to enroll 60 participants to assess the safety and efficacy of daily vosoritide administration over a 52-week period.
For children with hypochondroplasia, a Phase 3 long-term extension study, NCT07073014, is open for enrollment. This study aims to enroll 140 participants to further evaluate the long-term safety and efficacy of daily vosoritide doses.
Children with Noonan Syndrome experiencing inadequate growth, even after human growth hormone treatment, may be eligible for a Phase 2 study, NCT06668805. This trial is designed for 30 participants and will examine the effect of three different vosoritide doses on growth over six months, with long-term evaluation of efficacy and safety.
Vosoritide is also being studied for children with idiopathic short stature in a Phase 2 trial, NCT06382155. This study plans to enroll 100 children to evaluate the effects of multiple vosoritide doses and compare a therapeutic dose of vosoritide to human growth hormone, specifically in the United States.
Finally, a Phase 2 study, NCT05849389, is investigating vosoritide for short stature in individuals with Turner Syndrome. This trial aims to enroll 20 participants, exploring vosoritide as a potential option where growth hormone therapy may not fully address short stature.
Where to Participate
Clinical trials for vosoritide are actively recruiting across a wide geographic area, with study sites located in 62 facilities spanning 45 cities and 27 states. This broad reach helps ensure access for potential participants.
Some of the top locations with multiple recruiting sites include:
- Washington D.C., District of Columbia (5 sites)
- New York, New York (4 sites)
- California City, California (4 sites)
- Minneapolis, Minnesota (3 sites)
- Oakland, California (3 sites)
- Houston, Texas (3 sites)
- Los Angeles, California (3 sites)
- Chicago, Illinois (3 sites)
- Iowa City, Iowa (2 sites)
- Wilmington, Delaware (2 sites)
Eligibility for these studies generally includes individuals between the ages of 0 and 36 years, with all genders welcome. It is important to note that these trials are specifically for children and young adults with the conditions being studied, and healthy volunteers are not eligible.
Development Timeline
The development journey for vosoritide began on January 6, 2020, marking the start of its first clinical trial. Since then, a total of 10 trials have been initiated, with an overall target enrollment of 672 participants, reflecting a sustained effort to explore its potential.
Initially, vosoritide was investigated for conditions such as IBS-C and hyperphosphatemia. However, the research pipeline quickly expanded, demonstrating a broader therapeutic interest. The primary sponsor driving much of this research has been BioMarin Pharmaceutical, leading 7 of the trials, with additional contributions from other institutions like Roopa Kanakatti Shankar, MBBS, MS, and the University of California, San Francisco.
As development progressed, the focus broadened significantly to address various growth-related disorders. Vosoritide is now being studied for conditions including achondroplasia, MPS VI, Noonan Syndrome, Turner Syndrome, idiopathic short stature, and MPS IVA. The trials have advanced through different stages, with 6 studies in Phase 2, 2 in Phase 3, and one each in Phase 1/Phase 2 and Phase 2/Phase 3, indicating a progression through the rigorous clinical development process. The latest trial is projected to conclude by March 2, 2026, highlighting the ongoing commitment to understanding vosoritide's full potential.