BioMarin Pharmaceutical’s $270 million bet on Inozyme’s enzyme replacement therapy looks in trouble after the candidate only managed to hit one of the dual primary endpoints of a phase 3 study in children with a rare genetic disorder.
The biopharma evaluated the candidate, formerly known as INZ-701 and now called BMN 401, in a late-stage study of 27 children with ENPP1 deficiency. Children with this deficiency usually develop a type of rickets called autosomal-recessive hypophosphatemic rickets type 2, while adolescents and adults may develop softened bones.
The trial met one of the study’s co-primary endpoints by demonstrating a statistically significant increase in plasma inorganic pyrophosphate (PPi) at Week 52 compared with the control arm of conventional therapy.
But the study ran into trouble when it came to the other key goal of showing an improvement, as demonstrated by X-rays assessing skeletal healing. To make matters worse, BioMarin acknowledged that “no positive trends were observed” across the trial’s secondary endpoints, which included a score of rickets severity as well as body growth and weight gain.
BMN 401 was generally well-tolerated with no new safety signals reported, according to the company.
The mixed readout is a blow to BioMarin, which handed over $270 million to buy Inozyme in March 2025. Inozyme’s pipeline was led by BMN 401, and the trial had already kicked off by the time of the acquisition.
The idea was that giving BMN 401 to people who are missing or have mutated forms of the ENPP1 enzyme could reverse the effects of pathologic mineralization, such as calcification of the arteries, tendons and ligaments. Inozyme had already shared interim biomarker and anti-drug antibody data from the trial ahead of the deal, but it had struggled to convince public investors.
Buying Inozyme for $4 a share, more than twice the biotech’s closing price before news of the deal emerged, was part of a wider strategy by James Sabry, M.D., Ph.D., an ex-Roche dealmaker who BioMarin appointed as chief business officer in 2024.
The Inozyme acquisition was the first big deal of Sabry’s tenure, although BioMarin has gone on to secure rare disease compatriot Amicus Therapeutics in a $4.8 billion agreement.
Elsewhere, BioMarin has slimmed down its pipeline, including ending work last year on a preclinical phenylketonuria drug once touted as a potential successor to its approved med Palynziq.
In this morning’s release, BioMarin Chief R&D Officer Greg Friberg, M.D., wasn’t willing to call time on BMN 401 quite yet.
“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,” Friberg said.
“We are actively evaluating these data to determine the appropriate next steps,” he added. “ENPP1 deficiency is a devastating disease, particularly for infants, where mortality rates remain high and new treatment options are urgently needed.”