Clinical Trial to Evaluate HMI-103 for PKU

Previously, clinical-stage genetic medicines company Homology Medicines, Inc. (“Homology”) submitted an Investigational New Drug (IND) application to the FDA for HMI-103, an investigational gene editing therapy designed to treat phenylketonuria (PKU). According to First Word Pharma, the FDA accepted this IND. Now, Homology may move forward with a Phase 1 pheEDIT clinical trial to evaluate the single-dose therapy. This makes this the first-ever gene-editing therapy designed for PKU which has made it into clinical trials.


According to Homology, HMI-103 is given via a singular treatment and works to improve functional PAH expression within liver cells. Through this, the therapy helps metabolize phenylalanine. Additionally, HMI-103 works to integrate a working copy of the gene through a natural DNA reparation process and by inactivation of a defective gene.

This investigational, nuclease-free therapy uses AAVHSC15 to target a specific genomic area. Altogether, 9 patients will enroll in this burgeoning trial. Patients must be between the ages of 18-55, although younger individuals may be enrolled in future trials. During the Phase 1 pheEDIT clinical trial, researchers will evaluate 3 separate HMI-103 doses to figure out the recommended dosage for future studies.

Outside of HMI-103, Homology is also evaluating HMI-102, a gene therapy candidate, for adults with PKU. Within the Phase 2 pheNIX trial, researchers have found that:

  • HMI-102 is relatively safe and well-tolerated.
  • Treatment helps reduce phenylalanine levels within the body.

Phenylketonuria (PKU)

Caused by PAH gene mutations, phenylketonuria (PKU) is a rare genetic disorder and inborn error of metabolism. Normally, PAH helps to produce an enzyme called phenylalanine hydroxylase; in turn, this enzyme helps break down phenylalanine, an amino acid. In patients with PKU, phenylalanine begins to accumulate in the body, causing toxicity and serious health issues. Because phenylalanine can be found in various proteins and artificial sweeteners, patients must avoid high-protein diets. Some also use formula supplements. An estimated 1 in every 10-15,000 births has PKU. Symptoms typically appear within a few months following birth. These include:

  • Intellectual and developmental delays
  • Hyperactivity
  • Fair skin and eyes
  • Skin rashes
  • Reduced bone strength
  • Musty-smelling breath, skin, and urine
  • Microcephaly (abnormally small head)
  • Heart defects
  • Seizures
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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