Achondroplasia is the most common form of skeletal dysplasia, caused by a mutation in the FGFR3 gene, which inhibits normal bone growth. The clinical phenotype of achondroplasia is characterized by disproportionately short limbs, macrocephaly, prominent frontal bossing, and mid-face hypoplasia, accompanied by a depressed nasal bridge.
In 2023, the medication Vosoritide, under the brand name Voxzogo, was introduced in Georgia. This is the first approved drug that directly treats the underlying cause of achondroplasia rather than just the symptoms.
Vosoritide
Vosoritide is a modified analog of C-type Natriuretic Peptide (CNP), developed based on decades of fundamental scientific research. Its mechanism of action aims to correct the core pathogenesis of achondroplasia:
In achondroplasia, the mutation in the $FGFR3$ gene causes the protein to be constantly overactive. This protein acts as a “brake,” constantly sending an inhibitory signal that suppresses the development of cartilage cells (chondrocytes) and bone growth.
Vosoritide, as a CNP analog, binds to another specific receptor ($NPR-B$). As a result of this binding, it reduces the power of the $FGFR3$ inhibitory signal, which essentially neutralizes the “brake’s” effect.
Blocking this mechanism activates the bone growth process, consequently, Vosoritide resolves the problem caused by the genetic defect.
Georgian Children
Vosoritide is a very expensive medication. Depending on the dosage, the average price of one injection (based on US data) ranges around $1,000 USD. Treatment involves one daily injection and must continue as long as the child has growth potential. Naturally, securing full funding for such an expensive course of treatment was virtually impossible for the average Georgian family.
It was precisely because of this enormous financial barrier that Georgian parents of children with achondroplasia actively fought for the accessibility of Vosoritide in Georgia for a long time. Their tireless efforts ended successfully: this medication for the treatment of achondroplasia was introduced in Georgia in November 2023.
The drug’s introduction was preceded by the parents’ continuous fight. For example, Petre’s parents, along with other families, held protests outside the Ministry of Health at the end of 2023, and then spent 19 days and nights at the Government Administration demanding the drug’s inclusion in the state program. As a result of this struggle, on November 14, 2023, Vosoritide became accessible in Georgia.
Petre began receiving Vosoritide injections at the age of 9, which is considered an optimal period for the drug’s effectiveness. In his case, the result was prompt; he grew 8 centimeters in a year and a half. Growth is not the only positive change. Petre, who now administers the injections independently, notes that his leg pain when walking has also decreased. Thus, Vosoritide became a determinant not only of increased centimeters for Petre but also of a significant improvement in his quality of life.
New Innovative Medication – Navepegritide
Against the backdrop of Vosoritide’s success, research does not stop. A scientific review published in The Lancet, titled “New treatments for children with achondroplasia,” highlights a significant breakthrough in the treatment of achondroplasia.
Other variants of CNP with long-acting formulations, such as Navepegritide, are currently being developed.
Navepegritide is a medication created with the same principle as Vosoritide – it activates bone growth via the CNP (C-type Natriuretic Peptide) pathway. However, its innovativeness lies in the extended duration of its action, which potentially makes the medication more convenient for patients.
Unlike Vosoritide, which requires a daily injection, Navepegritide is designed to be administered subcutaneously only once a week. This change creates enormous comfort:
For parents: Adherence to the treatment regimen becomes much simpler, reducing daily stress.
For children: The reduced frequency of injections directly improves the child’s quality of life.
Large-scale clinical trials have fully confirmed the high effectiveness and safety of Navepegritide. The drug significantly increases the annual growth rate in children’s height.
As for safety, Navepegritide is generally well-tolerated, and side effects are mostly mild. It is especially noteworthy that there has been almost no high risk of symptomatic blood pressure decrease (hypotension) reported, which is a significant advantage for this class of medications.
Furthermore, Navepegritide not only affects height but also improves bone structure: it aids in the straightening of the lower limbs and increases the size of the protective spinal canal, which reduces the need for serious complications and surgical interventions characteristic of achondroplasia.
The drug manufacturer, Ascendis Pharma, has already submitted the final approval application to the FDA.
