Phase 2 results of Vosorotide for achondroplasia

BioMarin presented on the 20th April the updates for Vosoritide, the drug now in phase 2 for achondroplasia.

Before going further: What is a phase 2 in a clinical trial?

The development of a new medicine can be divided into 10 different steps and phase 2 is also known as the “Proof of Concept studies”, meaning that the drug is given to a larger group of people to see if it is effective and to further evaluate its safety.

Image from EUPATI

Average height children, with ages between 4 to 13 years old, usually growth around 6 cm/year while a child with achondroplasia grows around 4 cm/year. In this press release, BioMarin confirmed that the 10 children included in the 3rd group of the study (there are 4 groups in total in phase 2), with ages between 6 to 11, received for 12 months a dose of 15 μg/kg/day of Vosoritide.

This group of children were evaluated frequently and the results after 6 months with the drug were promissing, once they have grown 1,1 cm plus the natural growth. Now the results of the 10 children, 12 months after, become public: the 10 children, have grown 1,9 cm, plus the natural growth. So in one year, the results presented are an increase of 1,9 cm/year in 10 children with a 15 μg/kg/day, meaning this that the total annual average growth of this group (natural growth + growth induced by Vosoritide) was aproximately 6 cm a year that is identical to an annual average height child growth.

The children from groups 1 and 2, that were receiving lower dosis of vosorotide during the first 6 months and changed for the 15 μg/kg/day dosis in the following 6 months of the trial, have grown in average, during 12 months, 2.3 cm/year, plus the natural growth. This are very promissing results.

Another data revealed was the improvement of the upper to lower body ratio. What those this mean?

Achondroplasia is a form of disproportional dwarfism, meaning that one or more body parts are relatively larger or smaller in comparison to those of an average sized adult.

The lower body segment is the measurement of the length from the pubic point to the floor; the upper body segment is the height minus the lower body segment. The U/L ratio (upper body segment divided by the lower body segment) at birth is about 1.7. At age 3 years is about 1.3. In children greater than 7 years, it is aproxamately 1.0, with the upper body segment and lower body segment being about equal. Higher U/L ratios are noted in short-limb dwarfism. So the ideal is a ratio near 1.

The results BioMarin presented show slight but favorable changes observed in proportionality.

Relevant points presented for 12 months of Vosoritide:

- Remains generally well tolerated.
- Seems to keep its levels of action (this is based in a specific urinary exam).
- Still no existence of significant side effects. The most common treatment-related adverse events were injection site reactions (mild, as stated and in 90% of subjects) and asymptomatic hypotension (drop of the blood pressure – 40% of subjects)
- First safety data for the doble dose, 30 μg/kg/day, appears favorable.