BioMarin Discontinues Development of Therapy for ENPP1 Deficiency

Rare Daily Staff

BioMarin Pharmaceutical said it will discontinue development of its experimental enzyme replacement therapy for the rare, life-threatening genetic disorder ENPP1 deficiency following mixed phase 3 results reported in May.

The company made the announcement during its quarterly earnings report.

ENPP1 deficiency is a rare mineralization disorder that leads to calcification of soft tissues. About half of affected newborns die within the first year of life, while others may live into adulthood. The condition can cause hearing loss, arterial calcification, and complications involving the heart and brain.

BMN 401, a subcutaneous enzyme replacement therapy, had been viewed as a potential first-in-class treatment for ENPP1 deficiency. The condition can present in infancy as generalized arterial calcification of infancy (GACI), with mortality rates approaching 50 percent within the first six months of life. Survivors often develop rickets and other long-term complications.

BioMarin’s Phase 3 ENERGY 3 study met one of its two co-primary endpoints, demonstrating that BMN 401 significantly increased plasma inorganic pyrophosphate (PPi) levels through 52 weeks compared with conventional therapy. Low PPi is a key driver of disease pathology, contributing to abnormal calcification in blood vessels, soft tissues, and bones.

However, the therapy failed to show improvement in its second co-primary endpoint, Radiographic Global Impression of Change (RGI-C), a clinician-assessed measure of rickets severity. The company also reported no meaningful trends across secondary endpoints, including rickets severity scores and growth measures.

BioMarin acquired BMN 401 in 2025 through its $270 million purchase of Inozyme Pharma, which originally developed the enzyme replacement therapy under the name INZ-701. Following the acquisition, BioMarin rebranded the asset as BMN 401 and assumed responsibility for its late-stage clinical development, including the ENERGY 3 trial in children with ENPP1 deficiency.