BioMarin Pharmaceutical said its experimental enzyme replacement therapy BMN 401 met one of two primary goals in a late-stage clinical trial involving children with ENPP1 deficiency, a rare genetic condition.
The therapy, formerly known as INZ-701, was evaluated in a phase 3 study involving 27 children aged 1 to 12 years with ENPP1 deficiency. The condition is caused by changes in the ENPP1 gene that reduce plasma inorganic pyrophosphate (PPi), leading to damage to blood vessels, soft tissues, and bones. Children with the disorder typically develop autosomal-recessive hypophosphatemic rickets type 2, while adolescents and adults may develop softened bones.
BioMarin said BMN 401 achieved one of the trial’s co-primary endpoints by demonstrating a statistically significant increase in plasma PPi through Week 52 compared with a control arm receiving conventional therapy.
However, the therapy did not meet the second primary endpoint, which assessed skeletal healing through X-rays in children with rickets. The company said the treatment did not show improvement in a measure evaluating treatment impact in children with the bone disorder.
The company also reported no positive trends across secondary endpoints, including rickets severity scores and measures of growth such as height and weight gain. BioMarin said it did not observe meaningful improvement in rickets severity, body growth or weight gain.
BMN 401 was generally well tolerated, and the company reported no new safety signals during the study.
The result represents a setback for BioMarin following its $270 million acquisition of Inozyme in March 2025. The trial had already begun before the acquisition, and BMN 401 was the lead program in Inozyme’s pipeline. BioMarin acquired the company for $4 per share, more than double Inozyme’s closing price before news of the deal emerged.
The treatment was developed with the aim of replacing missing or mutated ENPP1 enzyme activity to reverse the effects of pathologic mineralization, including calcification of arteries, tendons, and ligaments. Before the acquisition, Inozyme had shared interim biomarker and anti-drug antibody data from the study, but struggled to convince public investors.
The acquisition marked the first major deal under James Sabry, M.D., Ph.D., who joined BioMarin as chief business officer in 2024 after previously working as a dealmaker at Roche. BioMarin later reached a $4.8 billion agreement involving Amicus Therapeutics and has also reduced parts of its pipeline, including ending work on a preclinical phenylketonuria drug previously viewed as a possible successor to its approved medicine Palynziq.
“We are disappointed that the significant increases in plasma PPi observed with BMN 401 did not translate into meaningful clinical improvements for children with ENPP1 deficiency,” said Greg Friberg, M.D., BioMarin’s chief research and development officer.
Friberg added that the company is actively evaluating the data to determine the appropriate next steps and said ENPP1 deficiency is a devastating disease, particularly for infants, where mortality rates remain high and new treatment options are urgently needed.
BioMarin Reports Mixed Outcomes in ENPP1 Deficiency Study
BioMarin has announced mixed results from its late-stage clinical trial evaluating BMN 401 for patients with ENPP1 deficiency. While the therapy successfully achieved one primary objective, the study failed to meet a major clinical endpoint, creating uncertainty about the future regulatory pathway for the treatment.
The latest update from BioMarin highlights the complexity of developing therapies for rare genetic disorders. Researchers involved in the study noted that although some patient improvements were observed, the overall clinical benefit did not fully meet expectations established during earlier development stages.
BioMarin Continues Focus on Rare Disease Innovation
The Phase 3 study was designed to evaluate the safety and effectiveness of BMN 401 in individuals suffering from ENPP1 deficiency, a rare inherited condition linked to abnormal bone mineralization and severe health complications. BioMarin has been actively investing in treatments for rare diseases and genetic disorders for many years.
Despite missing an important endpoint, BioMarin stated that the therapy demonstrated encouraging biological activity and measurable improvements in certain clinical markers. The company is expected to continue discussions with regulatory agencies regarding potential next steps and additional analyses.
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