RARE Daily

FDA Lifts Clinical Hold on Homology’s PKU Gene Therapy Trial

Rare Daily Staff

June 13, 2022

The U.S. Food and Drug Administration has lifted the clinical hold it placed on Homology Medicines’ pheNIX gene therapy clinical trial with investigational HMI-102, an experimental gene therapy for adults with the rare metabolic condition phenylketonuria.

Photo: Albert Seymour, president and chief scientific officer of Homology Medicines

The clinical hold on the pheNIX trial pertained to elevated liver function tests observed in the trial, which were all resolved with no hospitalizations required. Homology’s response to the FDA included changes to the protocol intended to enhance risk-mitigation measures and a new immunosuppression regimen with the T-cell inhibitor tacrolimus, which will be used in combination with a reduced duration of prophylactic steroids. The same approach is being used in Homology’s ongoing pheEDIT gene editing trial for PKU and juMPStart gene therapy trial for Hunter syndrome. Similar regimens have been shown to dampen the immune response to AAVs in the clinical setting.

The FDA noted in its response that Homology satisfactorily addressed all clinical hold issues identified in its letter of March 17, 2022.

PKU, or phenylalanine hydroxylase (PAH) deficiency, is a rare genetic disorder caused by a deficiency of the enzyme PAH. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems, and psychiatric symptoms. As a result of newborn screening efforts implemented in the 1960s and early 1970s, virtually all individuals with PKU under the age of 40 in countries with newborn screening programs are diagnosed at birth and treatment is implemented soon after.

“We believe our ability to quickly and successfully respond to the FDA is a testament to our experienced clinical and regulatory teams who also applied key learnings from the gene therapy field and our clinical program to update the pheNIX trial protocol,” said Albert Seymour, president and chief scientific officer of Homology Medicines. He said the company plans to provide an update on the program this fall.

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