A BioMarin Pharmaceutical deal last year brought the company a late-stage therapy that fit the company’s extensive enzyme replacement experience while also offering the potential to become the first treatment for an ultra-rare and fatal inherited disease. A pivotal study now has preliminary data, but with mixed results that raise questions about this program’s future.
The disease is a mouthful: ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) deficiency. It leads to the buildup of calcium in tissues and the walls of blood vessels. The cardiovascular complications mean that about half of babies born with ENPP1 deficiency don’t survive beyond six months, according to BioMarin. The disorder also leads to poor mineralization in bones, resulting in soft bones, also called rickets.
ENPP1 deficiency is caused by genetic mutations that lead to low levels of the disorder’s namesake enzyme, which is needed to produce inorganic pyrophosphate (PPi), a different enzyme that’s key for preventing calcification in tissues. BioMarin’s experimental therapy, BMN 401, is a fusion protein intended to increase levels of PPi.
Preliminary Phase 3 results reported Monday show the subcutaneously injected therapy led to a statistically significant increase in PPi levels measured at one year, meeting one of the main trial goals. But on the co-primary endpoint of assessing skeletal changes according to a rickets rating scale, no improvement was shown. BioMarin also said there were no positive trends on secondary trial goals, including a rickets severity score and measures of height, body length, and weight. Detailed safety data were not released but BioMarin said the study drug was well tolerated by the young patients with no new safety signals reported.
BioMarin previously said it expected to file regulatory submissions for BMN 401 in the second half of this year and launch the drug next year — if the data were positive. The next development could be the presentation of more detailed Phase 3 results, which the company said is planned for an upcoming medical meeting.
“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,” Greg Friberg, BioMarin executive vice president and chief research & development officer, said in a prepared statement. “We are actively evaluating these data to determine the appropriate next steps.”
BMN 401 came from the $270 million acquisition of Inozyme Pharma, a deal struck a little more than a year ago. In late 2025, BioMarin reached a $4.8 billion deal to buy Amicus Therapeutics, bringing two commercialized rare disease drugs projected to become blockbuster sellers.
BioMarin has been turning to business deals that bring late-stage and commercialized assets expected to achieve the revenue growth it had missed with some of its internal efforts. The most glaring miss might be Roctavian, which in 2023 became the first FDA-approved gene therapy for hemophilia A but went on to become a commercial failure. BioMarin’s efforts to place Roctavian with another company were unsuccessful and the biotech ended up voluntarily withdrawing the product from the market.
In a note sent to investors on Monday, Leerink Partners analyst Joseph Schwartz said the Amicus acquisition could support longer-term growth for BioMarin. Clarity about the outlook for the acquired Amicus assets and the potential synergies from the deal is expected in the coming quarters. But the future for BMN 401 is murky. Schwartz said the lack of clinical benefit raises questions about how the FDA would view the results.
“While ENPP1 deficiency remains a high unmet need indication and new treatment options are needed, we are cautious on the regulatory path forward at this point,” he said. “The company also stated that they are evaluating data to determine next steps. We look forward to detailed results from the study at an upcoming medical meeting which may provide more confidence in a path forward for the program.”
Photo: Bulat Silvia, Getty Images
