BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) just put out an update relating to its lead achondroplasia asset, Vosoritide, and the company is up a couple of percentage points on the data. This reaction isn’t really representative of the drug’s underlying potential, however. The data reinforces an efficacy readout of previous releases, and establishes a dose protocol for a pivotal trial in this indication, set to kick off before the end of 2016. With this trial in mind, and ahead of its initiation, here’s a look at what the drug involves and what the potential patient population looks like.

So, as mentioned, it’s called Vosoritide and it’s targeting achondroplasia, which is a form of dwarfism. We covered this indication a while back, but chances are that many reading will have missed that coverage, so it’s worth quickly recapping the science behind the condition.

Patients with achondroplasia don’t form cartilage properly, and this leads to a short stature (generally an average of 131 cm for males and 123 cm for females) and disproportionate limbs. In our bodies we have a protein called fibroblast growth factor receptor 3 (FGFR3). It’s coded by a gene of the same name, and it plays a key role in the development and growth of bones by promoting the formation of cartilage. The role is a sort of anti-promotional role. It downregulates bone and cartilage growth when activated, and it’s activated by proteins known as BFGRs. When a patient has achondroplasia, a mutated receptor formation (which results on the back of the mutated gene) causes the receptor in question to be constantly active. Constant activation results in constant down regulation of bone and cartilage formation, which in turn results in the shortened limbs and the small skeletal framework that characterizes the condition in question.

Now, we’ve got a peptide inside us called C-type natriuretic peptide (CNP), and this reduces the impact that FGFR3 has on bone growth. It’s a normal control mechanism in healthy individuals. BioMarin’s drug, Vosoritide, is an analog of this peptide. Basically the company has come up with a synthetic version of CNP that it hopes will have the same impact on the mutated FGFR3 receptors in patients with achondroplasia that biological CNP has on normal FGFR3 receptors in healthy patients.

So that’s the science, what about the data?

Well, the latest update relates to the final cohort of a pretty long running phase II trial, testing the drug in children with the condition. We won’t go in to the numbers in too much detail, but essentially across a range of doses, it looks as though the drug can accelerate growth by an average of 2 cm per year. The latest data confirmed this with a dose of 30 µg/kg/day, but similar results derived from two previous cohorts (the trial was a four total cohort trial) that demonstrated the average 2 cm acceleration at 7.5 µg/kg/day and 15 µg/kg/day respectively.

With these data in the bag, the company is putting together a phase III study that is going to carry forward using the middle of the above mentioned dosing regimens, 15 µg/kg/day. The logic behind this is simple – no need to risk any increased adverse events that might come about as the result of a higher dose regimen, when the drug has proven effective at a lower dose.

What are we looking for going forward?

BioMarin is setting up the phase III as we speak, and one important aspect is going to be the primary endpoint. The company believes the endpoint used in this study – change in growth velocity from baseline – would be a reasonable endpoint on which to base a registration application. However, this is not confirmed. As such we are looking for a confirmation of this endpoint being accepted by the FDA as part of the phase III protocol as a major catalyst. BioMarin has performed against this endpoint already (albeit in a small patient sample size) and we think doing so again would give the company its best chances of approval come application time.

What about patient population?

Around 1 in 25,000 live births are achondroplasia sufferers globally, and the company is targeting sufferers that are under 18 years old (this is not a fixed number, it is based on whether the patient’s plates are still open, which is just another way of saying can that patient’s bones grow any further?) These patients account for around 25% of the current population of achondroplasia sufferers in the US.

The phase III, as mentioned, is set to kick off before the end of the year.