Biomarin comes up short with vosoritide


After yesterday’s presentation of phase II data for vosoritide Biomarin can at least claim that its pivotal path has been clarified. But the fact that doubling the dose of the dwarfism project has fallen flat should cause investors to pause for thought.

Expectations for vosoritide are huge: the sellside reckons on it becoming Biomarin’s second-best selling drug in 2022, and with an NPV of $1.9bn it stands as the third-most valuable phase II asset across the entire biopharma industry. These high hopes will make it hard for Biomarin to shrug the setback off.

It was just over a year ago that vosoritide emerged as an important Biomarin pipeline asset, with initial phase II results with 15µg/kg per day beating expectations, and setting a high bar for future studies of a 30µg/kg dose (BioMarin stands tall with positive achondroplasia data, June 18, 2015).

The asset is in development for achondroplasia, a genetic mutation that is the most common cause of dwarfism. One of the most important findings of those initial data was the relative lack of a feared low blood pressure side effect, making doubling the dose a possibility, with the hope of allowing children to catch up fully in growth.

Double dose setback

However, based on further data presented yesterday at the American Society of Human Genetics meeting, this effort has failed.

The 30µg/kg dose did result in a statistically significant increase in mean growth velocity versus baseline – 46% after six months – but this was numerically no better than dosing at half this level. Two six-month 15µg/kg doses gave 65% and 50% increases, and one of these taken out to 12 months increased growth by 46%.

Children’s growth speed increased by roughly 2cm per year from baseline across all four cohorts. Again, the lack of new safety concerns at the higher dose – hypotension was mild and transient, and resolved without medical intervention, Biomarin said – was a relief, but will cut no ice without additional efficacy.

Of course, as with most rare disease trials, the cohorts were small, amounting to 30 patients in total. Thus it is hard to extrapolate the findings to the real-world setting, and Leerink analysts speculated that some patients might still try higher dosing.

But Biomarin has clearly taken the hint, saying the long-awaited phase III trial, due to start before the end of this year, would use 15µg/kg dosing, over one year and with a placebo group. Leerink also said it was unclear what additional information regulators might want; Stiefel analysts accepted that the theory about children catching up growth was dead in the water.

Most analysts reckon that achondroplasia is a market worth $1bn, and vosoritide’s 2022 sales are expected to reach $565m, according to sellside consensus compiled by EvaluatePharma. Increasing the success probability to 100% (it is currently 30%, in line with other phase II assets) makes the project a $6.1bn asset.

However, with the bull thesis now dispelled, it is far from clear how much of the blockbuster market vosoritide might ultimately capture.

To contact the writer of this story email Jacob Plieth in London at or follow @JacobPlieth on Twitter

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