BioMarin Pharmaceutical is continuing to slim down its pipeline, this time ending work on a preclinical phenylketonuria (PKU) drug once touted as a potential successor to its approved med Palynziq.
The company had originally been planning to seek an FDA nod later this year to take the therapy, dubbed BMN 390, into human trials. BioMarin’s chief R&D officer Gregory Friberg, M.D., told Fierce Biotech in February that BMN 390 was designed to improve on Palynziq.
But the biopharma revealed in its second-quarter earnings release Monday that, as part of a “regular evaluation of R&D programs,” the company has since determined BMN 390 “did not meet its target immunogenicity threshold for advancement.”
The program has therefore been discontinued, with employees redeployed within the company, BioMarin explained.
“The company remains committed to developing new therapies for people with PKU, with other projects underway across the organization,” the biopharma added.
BioMarin’s Palynziq, which was approved for adults with PKU in the U.S. in 2018, brought in $106 million in sales for the second quarter of 2025, a 20% year-over-year increase, according to yesterday’s release.
The company also said yesterday it remains on track to submit an application later this year for the FDA to expand Palynziq’s label to cover 12- to 17-year-olds following a phase 3 study.
With BMN 390, BioMarin had swapped out the polyethylene glycol of Palynziq for a long polymer dubbed POEGMA. The hope had been that using POEGMA would reduce immune reactions compared to Palynziq, while the compound’s lower viscosity was also meant to improve the experience of patients injecting it into themselves.
Palynziq continues to be the only enzyme substitute therapy for PKU that lowers physiological blood Phe levels to within the normal range. But potential competition has surfaced from Japanese pharma Otsuka Pharmaceutical, which picked up a clinical-stage PKU asset from Jnana Therapeutics that's taken orally.
Back in February, Friberg acknowledged that the PKU space had changed since Palynziq made its debut. At that point, BioMarin had “really built itself on molecules in areas where there were no other therapies available,” Friberg told Fierce at the time.
The removal of BMN 390 is only the latest example of BioMarin keeping a close eye on the viability of its pipeline. Last year, the company shook up its corporate structure, separating into three business units—skeletal conditions, enzyme replacement therapies and the gene therapy Roctavian—while also laying off 7% of its global workforce. This also involved ending work on candidates for hereditary angioedema, metabolic dysfunction-associated steatohepatitis, long QT syndrome and cardiomyopathy.
A recent addition to the company’s pipeline has been a phase 3-stage enzyme replacement therapy for children with ENPP1 deficiency, which was acquired as part of the $270 million buyout of Inozyme in May.