Vosoritide, sold under the brand name Voxzogo, is a medication used for the treatment of achondroplasia. The most common side effects include injection site reactions (such as swelling, redness, itching, or pain), vomiting, and decreased blood pressure. Achondroplasia is a genetic condition that causes severely short stature and disproportionate growth. The average height of an adult with achondroplasia is approximately four feet. People with achondroplasia have a genetic mutation that causes a certain growth regulation gene called fibroblast growth factor receptor 3 to be overly active, which prevents normal bone growth. Vosoritide works by binding to a specific receptor called natriuretic peptide receptor-B that reduces the growth regulation gene's activity and stimulates bone growth. Vosoritide was approved for medical use in the European Union in August 2021, and in the United States in November 2021. The US Food and Drug Administration considers it to be a first-in-class medication.

Medical uses

In the European Union, vosoritide is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

for the treatment of achondroplasia in people two years of age and older whose epiphyses are not closed. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In the United States, vosoritide is indicated to increase growth in children five years of age and older with achondroplasia and open epiphyses (growth plates).

Mechanism of action

Vosoritide works by binding to a receptor (target) called natriuretic peptide receptor type B (NPR-B), which reduces the activity of fibroblast growth factor receptor 3 (FGFR3). FGFR3 is a

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

that normally down-regulates

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck an ...

and bone growth when activated by one of the proteins known as acidic and basic fibroblast growth factor. It does so by inhibiting the development (

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation re ...

and differentiation) of

chondrocyte Chondrocytes (, from Greek χόνδρος, ''chondros'' = cartilage + κύτος, ''kytos'' = cell) are the only cells found in healthy cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteog ...

s, the cells that produce and maintain the cartilaginous matrix which is also necessary for bone growth. Children with achondroplasia have one of several possible FGFR3 mutations resulting in constitutive (permanent) activity of this receptor, resulting in overall reduced chondrocyte activity and thus bone growth. The protein

C-type natriuretic peptide Natriuretic peptide precursor C, also known as NPPC, is a protein that in humans is encoded by the ''NPPC'' gene. The precursor NPPC protein is cleaved to the 22 amino acid peptide C-type natriuretic peptide (''CNP''). Function Natriuretic pe ...

(CNP), naturally found in humans, reduces the effects of over-active FGFR3. Vosoritide is a CNP analogue with the same effect but prolonged half-life, allowing for once-daily administration.

Chemistry

Vosoritide is an

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analo ...

of CNP. It is a peptide consisting of the amino acids

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

and glycine plus the 37 C-terminal amino acids from natural human CNP. The complete peptide sequence is : P G Q E H P N A R K YKGANKKG L S KG C FGLKL DR IGS MSGLGC with a disulfide bridge between positions 23 and 39 (underlined). The drug must be administered by injection as it would be rendered ineffective by the digestive system if taken by mouth.

History

Vosoritide was developed by

BioMarin Pharmaceutical BioMarin Pharmaceutical Inc. is an American biotechnology company headquartered in San Rafael, California. It has offices and facilities in the United States, South America, Asia, and Europe. BioMarin's core business and research is in enzyme re ...

and got

orphan drug An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

status in the US as well as the European Union. The safety and efficacy of vosoritide in improving growth were evaluated in a year-long, double-blind, placebo-controlled, phase III study in participants five years and older with achondroplasia who have open epiphyses. In the study, 121 participants were randomly assigned to receive either vosoritide injections under the skin or a placebo. Researchers measured the participants' annualized growth velocity, or rate of height growth, at the end of the year. Participants who received vosoritide grew an average 1.57 centimeters taller compared to those who received a placebo. The US Food and Drug Administration (FDA) granted the approval of Voxzogo to BioMarin.

Society and culture

Controversy

Some people with achondroplasia, as well as parents of children with this condition, have reacted to vosoritide's study results by saying that dwarfism is not a disease and consequently does not need treatment.

Research

Vosoritide has resulted in increased growth in a clinical trial with 26 children. The ten children receiving the highest dose grew in six months, compared to in the six months before the treatment ( p=0.01). The body proportions, more specifically the ratio of leg length to upper body length – which is lower in achondroplasia patients than in the average population – was not improved by vosoritide, but not worsened either.>

References

External links

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