BioMarin Pharmaceutical has reported preliminary results from a pivotal study of its experimental therapy, BMN 401, aimed at treating the ultra-rare and life-threatening ENPP1 deficiency. While the study demonstrated a statistically significant increase in plasma levels of inorganic pyrophosphate (PPi) over one year, it raised concerns about the future of the program as no clinical improvements were observed on the primary evaluation metric related to skeletal changes.
ENPP1 deficiency, characterized by mutations leading to inadequate levels of the ENPP1 enzyme essential for producing PPi, results in calcium accumulation in tissues and cardiovascular complications. According to BioMarin, nearly half of infants born with this disorder do not survive past six months. The condition is also linked to poor bone mineralization, resulting in rickets.
The Phase 3 trial’s results, released on Monday, indicated that the subcutaneous injection of BMN 401 met one of its key objectives by significantly increasing PPi levels. However, the primary endpoint—a skeletal assessment based on rickets severity—showed no improvement. Additionally, no positive trends were noted in secondary endpoints, which included measures of rickets severity, height, length, and weight. Though comprehensive safety data has yet to be disclosed, BioMarin noted the therapy was generally well-tolerated, with no new safety signals reported.
Previously, BioMarin stated it aimed to submit regulatory filings for BMN 401 in the second half of this year, with a potential drug launch in 2024, contingent on positive data. Further results from the Phase 3 trial are expected to be presented at an upcoming medical meeting.
Greg Friberg, BioMarin’s executive vice president and head of research and development, expressed disappointment that the significant increases in plasma PPi levels did not translate into meaningful clinical outcomes for children with ENPP1 deficiency. He stated the company is actively assessing the trial data to determine appropriate next steps.
BMN 401 was acquired from Inozyme Pharma for $270 million just over a year ago. In late 2025, BioMarin also entered into a $4.8 billion agreement to purchase Amicus Therapeutics, which will provide commercialized drugs for rare diseases expected to boost future revenues.
In light of some recent setbacks, including the commercial failure of Roctavian, the first FDA-approved gene therapy for hemophilia A, BioMarin has pursued business deals that deliver development-stage and marketed assets. Roctavian, after a disappointing market performance, was ultimately withdrawn from circulation.
In an investor note issued on Monday, Joseph Schwartz, an analyst at Leerink Partners, emphasized the potential growth from Amicus and the need for more clarity on its acquired assets and their potential synergies in the coming quarters. However, he criticized the lack of clinical benefit observed with BMN 401, raising questions about the FDA’s evaluation of the results.
Schwartz noted that while ENPP1 deficiency remains an area of unmet medical need, the pathway forward for BMN 401 appears uncertain. He highlighted anticipation for detailed Phase 3 results during the upcoming medical meeting, as these could provide further insights into the program’s future.
Photo: Bulat Silvia, Getty Images
