BioMarin Pharmaceutical has reported that its pivotal Phase III ENERGY 3 trial assessing BMN 401 in children aged one to 12 years with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) deficiency met one co-primary endpoint.

This rare, serious and progressive genetic condition leads to reduced plasma inorganic pyrophosphate (PPi) levels, causing progressive damage to the blood vessels, soft tissues and bones.

The controlled open-label, randomised (2:1), multi-centre trial met the endpoint showing BMN 401 treatment led to statistically significant increases in plasma PPi levels through week 52 against the conventional therapy control group.

However, the study failed to meet the second co-primary endpoint, as there was no related improvement in Radiographic Global Impression of Change (RGI-C) scores, an assessment of clinical impact in paediatric rickets.

The company reported no positive trends across secondary endpoints, including Rickets Severity Score (RSS) and growth Z-score (reflecting height/body length and weight).

BMN 401 was found to be generally well-tolerated, and no new safety signals were identified.

BioMarin Pharmaceutical executive vice-president and chief research and development officer Greg Friberg said: “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. We are actively evaluating these data to determine the appropriate next steps.

“ENPP1 deficiency is a devastating disease, particularly for infants, where mortality rates remain high and new treatment options are urgently needed. We are deeply grateful to the children, families, investigators and study teams who are participating in this trial.”

Previously known as INZ-701, BMN 401 is a subcutaneous enzyme replacement therapy candidate developed to treat ENPP1 deficiency.

The trial aimed to evaluate both efficacy and safety in the paediatric cohort.

A total of 27 children were enrolled in the ENERGY 3 study as of January 2025.

In April 2025, BioMarin Pharmaceutical reported that the multi-centre Phase III PEGASUS trial of Palynziq (pegvaliase-pqpz) met its primary efficacy endpoint, showcasing a reduction in blood phenylalanine (Phe) levels in adolescents with phenylketonuria (PKU) against only diet.