BioMarin down as FDA puts clinical hold on BMN 307 trial

US biotech BioMarin Pharmaceutical’s (Nasdaq: BMRN) shares were down more than 10% at $76.25 pre-market today, after it announced on Sunday that the US Food and Drug Administration (FDA) placed a clinical hold on the BMN 307 Phearless Phase I/II study.

The Phearless study is evaluating BMN 307, an investigational AAV5-phenylalanine hydroxylase (PAH) gene therapy, in adults with phenylketonuria (PKU). The FDA's clinical hold was based on interim safety findings from a pre-clinical, non-GLP pharmacology study.

The company carried out this pre-clinical study to understand the durability of BMN 307 activity in mice bearing two germline mutations, which may predispose the mice to the development of malignancy. One mutation eliminated the PAH gene that's missing in PKU and the second rendered the animals immunodeficient. Of 63 animals treated, six of seven animals administered BMN 307 at the highest dose group (2e14 Vg/kg) had tumors on liver necropsy 52 weeks after dosing with evidence for integration of portions of AAV vector into the genome. No lesions were observed in any mice at 24 weeks. Five of these animals had adenomas and one had a hepatocellular carcinoma (HCC). The translatability of these findings to humans is uncertain and under further investigation.