The Food and Drug Administration (FDA) has placed a clinical hold on the phase 1/2 trial evaluating HMI-102 in adults with phenylketonuria (PKU).

HMI-102 is a gene editing candidate for PKU designed as a one-time, in vivo treatment that delivers functioning PAH (phenylalanine hydroxylase) genes to the liver. The open-label, randomized, concurrently-controlled, dose escalation pheNIX study ( Identifier: NCT03952156) is evaluating the efficacy and safety of HMI-102 administered intravenously in adults with PKU due to PAH deficiency. 

The decision was made to place a clinical hold on the pheNIX study due to the need to modify risk mitigation measures in response to observations of elevated liver function tests. The Company expects to receive an official clinical hold letter within 30 days and will provide an update pending further clarity from the FDA.

“We look forward to working with the FDA to address the Agency’s questions and feedback once we receive the letter,” said Arthur Tzianabos, PhD, President and CEO of Homology Medicines. “This hold on our PKU gene therapy trial is based on clinical observations in the pheNIX study and does not relate to CMC/manufacturing capabilities or Homology’s other clinical programs. We plan to provide next steps once we have more information following our FDA interactions.”

The Company is also evaluating HMI-103, a gene editing candidate, in adults with classical PKU due to PAH deficiency in the phase 1 pheEDIT trial ( Identifier: NCT05222178), and HMI-203, an investigational gene therapy, in adults with Hunter syndrome in the phase 1 juMPStart trial ( Identifier: NCT05238324).


Homology Medicines provides an update on pheNIX gene therapy trial for adults with PKU. News release. Homology Medicines, Inc. February 18, 2022. Accessed February 22, 2022.