SAN RAFAEL, Calif. – BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today announced results from the pivotal Phase 3 ENERGY 3 trial evaluating BMN 401 in children aged 1-12 with ENPP1 deficiency, a rare, serious and progressive genetic condition. Deficiency in ENPP1 function results in a decrease in plasma inorganic pyrophosphate (PPi) that can lead to progressive damage to blood vessels, soft tissues and bones.
The study met one co-primary endpoint, showing treatment with BMN 401 resulted in statistically significant increases in plasma PPi through week 52 compared to the conventional therapy control arm in children with ENPP1 deficiency. However, the study did not meet its other co-primary endpoint as there was no corresponding improvement in Radiographic Global Impression of Change (RGI-C) scores, an important measure of treatment impact in children with rickets. Additionally, no positive trends were observed across secondary endpoints, including Rickets Severity Score (RSS) and growth Z-score (height/body length and weight). BMN 401 was generally well-tolerated with no new safety signals reported.
“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., Executive Vice President and Chief Research & Development Officer at BioMarin. “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.”
Detailed results from the ENERGY 3 study will be presented at an upcoming medical meeting.
About BMN 401 and ENERGY 3
BMN 401 (formerly INZ-701) is a potential first-in-class, subcutaneous enzyme replacement therapy for the treatment of people with ENPP1 deficiency.
ENERGY 3 is a Phase 3 multicenter randomized (2:1) controlled open-label clinical trial designed to evaluate the efficacy and safety of BMN 401 in children ages 1-12 with ENPP1 deficiency. Change from baseline in PPi through week 52 and RGI-C global score at week 52 are co-primary endpoints in this study. Following discussions with health authorities, RGI-C was added as a co-primary endpoint to assess clinically meaningful functional improvement in children with ENPP1 deficiency.
Key secondary endpoints include change from baseline in Rickets Severity Score (RSS), change from baseline in growth Z-score (height/body length and weight), and measurements of BMN 401 serum concentration and enzyme activity. Enrollment in ENERGY 3 was completed in January 2025, with the inclusion of 27 pediatric participants.
For more information, please visit clinicaltrials.biomarin.com.
About ENPP1 Deficiency
ENPP1 deficiency is a rare and lifelong genetic condition caused by changes in the ENPP1 gene, leading to progressive damage to blood vessels, soft tissues and bones. Infants with this condition are often diagnosed with generalized arterial calcification of infancy (GACI) Type 1, and about 50% of them do not survive beyond six months. Children with ENPP1 deficiency typically develop a type of rickets called autosomal-recessive hypophosphatemic rickets type 2 (ARHR2), while adolescents and adults may develop osteomalacia (softened bones), both of which may cause pain and difficulty with movement. Individuals may also experience hearing loss, calcification in arteries and joints, and heart problems.
About BioMarin
BioMarin is a leading, global rare disease biotechnology company focused on delivering medicines for people living with genetically defined conditions. Founded in 1997, the San Rafael, California-based company has a proven track record of innovation, with a portfolio of commercial therapies and a strong clinical and preclinical pipeline. Using a distinctive approach to drug discovery and development, BioMarin seeks to unleash the full potential of genetic science by pursuing category-defining medicines that have a profound impact on patients. To learn more, please visit www.biomarin.com.
BioMarin® is a registered trademark of BioMarin Pharmaceutical Inc.
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