BioMarin’s discontinued drug showed biomarker benefits in a Phase 3 study for ENPP1 deficiency but these failed to translate to clinical improvements.
BioMarin will no longer invest in an investigational enzyme replacement therapy following a disappointing late-stage showing earlier this year.
The asset, dubbed BMN 401, was being studied in the Phase 3 ENERGY trial for ENPP1 deficiency, a rare metabolic disease that involves a range of symptoms, including early-onset osteoporosis, the calcification of tendons and a higher risk of cardiovascular death.
The candidate came to BioMarin in May 2025 as the centerpiece of its $270 million takeover of Inozyme Pharma. A year later, however, the asset turned out to be a disappointment, meeting only one of two key endpoints in ENERGY. While BMN 401 significantly lowered levels of a key disease marker, this effect failed to translate into clinical benefit for patients.
The ENERGY failure has prompted BioMarin to discontinue the development of BMN 401 across all indications, according to the company’s second quarter earnings report released on Thursday. In addition to ENPP1 deficiency, Inozyme had previously been testing the molecule for ABCC6 deficiency and calcific uremic arteriopathy, both rare diseases. BioMarin no longer lists any active program in these indications.
Other than the discontinuation, BioMarin reported positive earnings results this quarter. Revenues climbed 20% year-on-year to hit $990 million, the biopharma reported. BioMarin’s product portfolio was led by the achondroplasia medicine Voxzogo, which brought in $253 million.
Of note, Voxzogo sales continued to grow—14% versus the same period in 2025—despite the entry of a key competitor: Ascendis Pharma’s Yuviwel, which won FDA approval in achondroplasia, the most common cause of dwarfism, this past March. Ascendis is scheduled to present its second quarter earnings on Aug. 13.
“Voxzogo continues to offset any impact with growth in the <2 [years] population and in the ex-US population, which comprises the majority of revenues,” Stifel analysts wrote in a note on Friday. “The next couple quarters will be key here in determining the competitive impact to BioMarin.”
In October last year, in anticipation of Yuviwel’s approval, BioMarin withdrew a previously announced goal of hitting $4 billion in revenue by 2027—a decision driven largely by the impact of potential challengers to Voxzogo. On Thursday, however, BioMarin’s confidence in Voxzogo appeared to grow, raising full year sales guidance from a range of $975 million to $1.02 billion to a minimum of $1 billion with the potential to reach $1.05 billion.
Aside from Ascendis, BridgeBio Pharma is also advancing on the achondroplasia market with its investigational pill dubbed infigratinib. Data released in late June showed that aside from boosting growth in children, infigratinib also improved body proportionality, a finding that could help the drug stand out in the achondroplasia arena. A regulatory filing for infigratinib is planned for the third quarter, with a potential launch in early to mid-2027.
