BioMarin Pharmaceutical Inc. has released results from its pivotal Phase III ENERGY 3 trial for children aged 1 to 12 with ENPP1 deficiency. The drug achieved one co-primary endpoint: a statistically significant increase in plasma inorganic pyrophosphate concentration at 52 weeks compared to the standard-of-care control group.

However, the trial failed to meet the other co-primary endpoint, with no improvement observed in the Radiographic Global Impression of Change score, which measures the severity of rickets. Furthermore, no positive trends were noted in key secondary endpoints, including the Rickets Severity Score and growth Z-scores. BMN 401 was generally well-tolerated, with no new safety signals reported.

Greg Friberg, Executive Vice President and Chief Research and Development Officer at BioMarin, expressed disappointment that the significant biochemical improvements with BMN 401 did not translate into meaningful clinical benefits for the children. The company is actively evaluating the data to determine the next steps. Following this news, BioMarin's stock price fell approximately 2.7%. H.C. Wainwright subsequently lowered its price target from $55 to $50 and removed BMN 401 from its model.

ENPP1 deficiency is a rare genetic disorder caused by variants in the ENPP1 gene, leading to progressive damage to blood vessels, soft tissues, and bones. In infancy, it can present as Generalized Arterial Calcification of Infancy type 1, with about 50% of affected infants dying within six months. In childhood, it typically develops into Autosomal Recessive Hypophosphatemic Rickets type 2. BMN 401 is a potential first-in-class subcutaneous enzyme replacement therapy designed to correct ENPP1 enzyme deficiency. The ENERGY 3 trial enrolled a total of 27 children, completing enrollment in January 2025. Detailed study results will be formally presented at upcoming medical conferences.