Homology Medicines announces FDA clearance HMI-102 IND
Homology Medicines announced that the FDA has provided clearance for Homology to begin its Phase 1/2 pheNIX clinical trial with HMI-102, a one-time gene therapy candidate for adults with the rare genetic disease phenylketonuria, or PKU, an inborn error of metabolism. Homology has been working closely with multiple clinical sites in the U.S. to prepare for potential initiation of the pheNIX trial, which is designed to evaluate the safety and efficacy of the investigational gene therapy in a randomized, concurrently-controlled, dose-escalation study in adult patients with classic PKU. HMI-102 is designed to use one of Homology's proprietary human hematopoietic stem-cell derived adeno-associated virus vectors, or AAVHSCs, to deliver a functional copy of the phenylalanine hydroxylase, or PAH, gene to the liver cells, where there is a missing or mutated PAH gene. This in vivo gene therapy approach is intended to enable the production of the PAH enzyme responsible for metabolizing phenylalanine, or Phe. People with PKU are not able to metabolize Phe properly resulting in elevated levels of Phe and if left untreated, can lead to severe neurological impairment. Phe reduction is an established clinical endpoint for PKU registrational trials. Homology's IND package contained preclinical data demonstrating that HMI-102 restored the normal biochemical pathway, including data showing that treatment with HMI-102 lowered serum Phe to normal levels within one week, which was durable for the lifespan of the murine model and lowered brain Phe to normal levels. HMI-102 also increased tyrosine, brain 5-hydroxyindoleacetic acid and changed coat color, indicating production of melanin.