Gene Therapy for Phenylketonuria: Homology & Biomarin Race to Bring Single Dose Treatment To Market


Phenylketonuria (PKU) is a genetic disorder of liver metabolism that arises primarily from the loss of function mutation of PAH gene encoding the hepatic enzyme phenylalanine (Phe) hydroxylase (PAH). Enzyme PAH converts Phe to produce tyrosine (Tyr) and subsequently funneled into other metabolic pathways.  
Lack of functional PAH results in hyperphenylalaninemia after dietary intake of protein, causing elevated systemic Phe levels. In high levels of Phe, patients show neurocognitive impairment and behavior problems. The classical PKU results in progressive, irreversible neurological impairment during infancy and early childhood, if left untreated. The characteristic features of the PKU include hypopigmentation in skin, hair, and eyes; eczema; growth retardation; and a mousy odor caused by the accumulation of phenylacetate and phenyllactate.

Market Analysis of PKU

The global phenylketonuria treatment market size was valued at USD 445.8 million in 2018 and is expected to register a CAGR of 11.0% from 2019 to 2026. The increasing prevalence of PKU across the globe is estimated to accelerate market growth. According to the Genetics Home Reference, 1 in 10,000 to 15,000 cases of PKU occurs in newborns in the U.S. In Europe, some countries have a high incidence rate of PKU, such as 1 in every 4500 babies in Ireland and 1 in 4,000 of individuals in Turkey, are suffering from the target disease.

Gene Therapy Approach

The investigation gene therapy is intended to deliver the PAH cDNA into the liver tissue of PAH deficient subject. The PAH transgene may produce sufficient PAH enzyme into the target tissue and normalize the Phe level.

Homology Medicine AAVHSC-15 PAH for treatment of PKU

HMI 102 is an investigational gene therapy intended to integrate the gene for the functional copy of PAH into the liver cells. The clinical study is being conducted to evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. (Learn More)

Biomarin AAV5-PAH for treatment of PKU

BMN-307 is an investigational gene transfer therapy intended to deliver its phenylalanine hydroxylase (PAH) gene to the liver tissue for the production of PAH enzyme protein. Biomarin is conducting a Phase 1/2 clinical trial (PHEARLESS) to evaluate the safety and efficacy of AAV-PAH gene therapy in subjects with PKU. (Learn More)

Sangamo Therapeutics: Sangamo's PKU gene therapy is at preclinical stage, therefore not covered. 

RTX-134, SYNB1618, and CNSA-001