After being hit by safety issues and subpar results in another trial, BioMarin’s Phase 3 test of Voxzogo for a rare skeletal disorder called hypochondroplasia showed efficacy “solidly above” what the drug has shown for achondroplasia, which causes dwarfism.
BioMarin’s achondroplasia drug Voxzogo significantly improved growth in a late-stage study of kids with hypochondroplasia, a rare and genetic skeletal disorder that leads to short stature. The readout delivers a much-needed win for the biotech’s rare disease portfolio, which in recent months has been battered by Voxzogo-linked safety concerns and a failed Phase 3 trial for an investigational enzyme replacement therapy.
With Voxzogo improving annualized growth velocity by 2.33 cm per year versus placebo, analysts at Stifel said the result “comes in solidly above what Voxzogo demonstrated in” late-stage development for achondroplasia, a rare genetic disorder that causes dwarfism in children and for which Voxzogo was approved in November 2021.
Voxzogo delivered a “bigger effect than expected” in the Phase 3 CANOPY-HCH-3 study, the firm said in its Wednesday afternoon note. BioMarin plans to file for Voxzogo’s approval in this indication in the third quarter, and Stifel said they expect the FDA to grant it.
Aside from growth velocity, CANOPY-HCH-3 also showed significant improvements in standing height and arm span, which according to Stifel “is a key secondary endpoint that has important functional implications.” The biotech, however, did not provide specific data for these endpoints in its Wednesday release, instead promising to do so at an upcoming scientific congress.
CANOPY-HCH-3’s “data are clearly better than expected and we thus think approval here is largely de-risked,” Stifel continued. Still, “it remains somewhat unclear to us how big this market really is.” The firm noted that hypochondroplasia “has a lower diagnosis rate versus achondroplasia as the phenotype is often less severe.”
“At the very least this is a market that probably needs to be built,” the analysts added.
Jefferies agreed, writing in a note on Wednesday that hypochondroplasia “remains underdiagnosed.” Though with the rise of genetic testing, “diagnostic rates will increase,” the analysts added. Jefferies forecasts $1 billion in peak sales for hypochondroplasia and achondroplasia, but concedes that this seems “conservative” given diagnosis levels.
A CNP analog, Voxzogo became the first-ever FDA-approved therapy for achondroplasia more than four years ago. There are currently no approved therapies for hypochondroplasia, according to BioMarin.
Expanding into hypochondroplasia—despite it being an uncharted market—could give BioMarin a commercial edge over Ascendis Pharma, which in March of this year won the FDA’s approval for its own achondroplasia asset Yuviwel. BioMarin has previously conceded that competitive pressures, from Yuviwel and other companies working on achondroplasia, would be substantial—at least enough to walk back a previous revenue target of hitting $4 billion by 2027.
Voxzogo made $927 million in net revenues last year, a 26% year-on-year growth.
Days after Yuviwel’s approval, BioMarin suspended studies of Voxzogo in Turner syndrome, SHOX-deficiency and aggrecan deficiency due to several cases of slipped capital femoral epiphysis detected in certain patients treated with the drug. The pressure has only piled on for BioMarin, which earlier this week reported that its enzyme replacement therapy BMN 401 showed no clinical benefit in a Phase 3 study of ENPP1 deficiency.
