BioMarin Pharmaceutical has discontinued development of BMN 390, a preclinical phenylketonuria (PKU) candidate, after determining that the compound did not meet its immunogenicity target.
BMN 390 had been designed as a potential follow-up to Palynziq, BioMarin’s approved PKU treatment. The company had initially planned to submit an Investigational New Drug (IND) application to the U.S. Food and Drug Administration in the second half of 2025. Gregory Friberg, M.D., BioMarin’s chief research and development officer, stated in February that BMN 390 was intended to improve on Palynziq. In a previous update, BioMarin noted that the therapy was modified to reduce the risk of anaphylaxis and lower immunogenicity, with the potential to enhance drug exposure and decrease hypersensitivity.
The therapy featured a substitution of Palynziq’s polyethylene glycol component with a polymer called POEGMA, which was intended to reduce immune response and lower viscosity to improve the self-injection experience.
However, in its second-quarter update, BioMarin reported that BMN 390 “did not meet its target immunogenicity threshold for advancement.” As a result, the program has been discontinued, and employees working on the asset have been reassigned to other roles within the company. BioMarin described this decision as part of its “regular evaluation of R&D programs.”
Despite the discontinuation, the company stated, “The company remains committed to developing new therapies for people with PKU, with other projects underway across the organization.”
Palynziq, which was approved in 2018 for adults with PKU, generated $106 million in revenue during the second quarter of 2025, representing a 20% increase from the same period the previous year. The company said it is preparing to apply later this year to expand Palynziq’s approved use to include patients aged 12 to 17, following a phase 3 study.
At present, Palynziq is the only enzyme replacement therapy available for PKU that reduces physiological blood phenylalanine levels to within the normal range. However, other treatments are emerging in the space. Otsuka Pharmaceutical has acquired a clinical-stage, orally administered PKU therapy from Jnana Therapeutics, and last week, PTC Therapeutics’ Sephience received FDA approval. Sephience, indicated for both adults and children, was approved to treat hyperphenylalaninemia in patients as young as one month. Phase 3 data showed a 63% reduction in phenylalanine levels among patients treated with Sephience.
Truist analysts, in a note released Tuesday morning, stated that the removal of BMN 390 “adds worry to BioMarin’s PKU business.” They noted that the launch of Sephience in the U.S. could create pressure on Palynziq.
The termination of BMN 390 is part of a broader review of pipeline programs at BioMarin. In 2024, the company restructured into three business segments—skeletal conditions, enzyme replacement therapies, and the gene therapy Roctavian—and implemented a workforce reduction of 7%. This restructuring also included halting programs targeting hereditary angioedema, long QT syndrome, cardiomyopathy, and metabolic dysfunction-associated steatohepatitis.
In May, BioMarin added a new candidate to its pipeline: a phase 3-stage enzyme replacement therapy for children with ENPP1 deficiency, acquired through its $270 million acquisition of Inozyme.
In the second quarter of 2025, BioMarin reported total revenues of $825 million, representing a 17% year-over-year increase. Analysts from William Blair attributed the earnings beat to higher-than-expected sales of enzyme therapies. Voxzogo, used to treat achondroplasia, generated $221 million with a 20% year-over-year increase, while Vimizim, for mucopolysaccharidosis type IVA, brought in $215 million following a 21% rise from the previous year.
