BioMarin Reports Mixed Phase 3 Results for BMN 401 in Rare ENPP1 Deficiency

Rare Daily Staff

BioMarin Pharmaceutical reported mixed results from its pivotal phase 3 ENERGY 3 trial of BMN 401, an experimental enzyme replacement therapy for children with ENPP1 deficiency, a rare and life-threatening genetic disorder.

The 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.

“While we observed significant increases in PPi, these biochemical improvements did not translate into meaningful clinical benefit,” said Greg Friberg, BioMarin’s chief research and development officer. “We are evaluating these data to determine next steps.”

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

BioMarin acquired BMN 401 in 2025 through its 270 million dollar purchase of Inozyme Pharma, which had 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.

The ENERGY 3 trial enrolled 27 pediatric patients aged 1 to 12 in a randomized, open-label design. The addition of RGI-C as a co-primary endpoint followed discussions with regulators to better capture clinically meaningful outcomes.

Despite the lack of clinical efficacy signals, BMN 401 was generally well tolerated, with no new safety concerns identified.

BioMarin said it plans to present detailed results from the study at an upcoming medical meeting as it considers the future of the program.