BioMarin Discontinues Preclinical PKU Drug, Refocuses Pipeline

BioMarin Pharmaceutical Inc. has announced the discontinuation of its preclinical phenylketonuria (PKU) drug, BMN 390, which was once considered a potential successor to the company's approved medication, Palynziq. This decision comes as part of BioMarin's ongoing efforts to streamline its research and development pipeline.

BMN 390 Development Halted

The company revealed in its second-quarter earnings release that BMN 390 "did not meet its target immunogenicity threshold for advancement." Originally slated for an FDA investigational new drug (IND) application later this year, the program has now been terminated. BioMarin's Chief R&D Officer, Gregory Friberg, M.D., had previously highlighted BMN 390's potential improvements over Palynziq, particularly in terms of reduced immune reactions and improved patient experience due to lower viscosity.

BMN 390 utilized a novel polymer called POEGMA instead of the polyethylene glycol found in Palynziq. This change was intended to address some of the challenges associated with Palynziq while maintaining its efficacy in lowering blood phenylalanine levels in PKU patients.

Palynziq Performance and Future Plans

Despite the setback with BMN 390, BioMarin's Palynziq continues to show strong performance. The drug, approved for adults with PKU in the U.S. in 2018, generated $106 million in sales during the second quarter of 2025, representing a 20% year-over-year increase.

BioMarin remains committed to expanding Palynziq's reach, with plans to submit an application later this year for FDA approval to extend its use to patients aged 12 to 17. This follows a successful phase 3 study in this age group.

Strategic Pipeline Management

The discontinuation of BMN 390 is part of a broader strategy at BioMarin to focus its resources on the most promising candidates. In recent years, the company has made several moves to optimize its pipeline:

1. In 2024, BioMarin restructured its organization into three business units: skeletal conditions, enzyme replacement therapies, and gene therapy (Roctavian).
2. The company reduced its global workforce by 7% as part of this reorganization.
3. Development was halted on candidates for hereditary angioedema, metabolic dysfunction-associated steatohepatitis, long-QT syndrome, and cardiomyopathy.
4. In May 2025, BioMarin acquired Inozyme for $270 million, adding a phase 3-stage enzyme replacement therapy for children with ENPP1 deficiency to its pipeline.

These strategic decisions reflect BioMarin's evolving approach in a changing competitive landscape, particularly in the PKU space where new entrants like Otsuka Pharmaceutical are developing oral therapies.