Prime Medicine doses first patient in in-body prime-editing trial for Wilson disease

First patient dosed

PM577a is a one-time intravenous infusion designed to correct the H1069Q mutation in the ATP7B gene inside liver cells. Prime Medicine described the dosing as the first clinical use of an in vivo prime-editing therapy.

The open-label Phase 1/2 study, identified as Prime-0201 and NCT07748403, is evaluating ascending doses in adults and adolescents with Wilson disease. The initial participants are adults who are clinically stable on standard treatment, Prime Medicine said. Every participant must have at least one H1069Q allele.

The milestone does not show that the treatment works. No clinical safety, copper-control or liver-function results were available when Prime Medicine announced the dosing. Researchers must still establish whether enough liver cells receive the intended edit and whether unintended genetic changes or immune reactions occur.

How PM577a is designed to work

PM577a packages prime-editing components in lipid nanoparticles, the delivery technology also used in COVID-19 mRNA vaccines. Prime Medicine designed the particles to reach liver cells and deliver the gene-editing tool. The company aims for a durable effect from one dose.

Prime editing was first described in 2019. It combines a modified CRISPR-associated protein with a reverse transcriptase enzyme and a guide molecule that identifies the target and carries instructions for the edit. Conventional CRISPR-Cas9 cuts both DNA strands and relies on the cell's repair machinery, which can insert or delete unwanted bases. Prime editing is designed to cut one strand, not both, and to make substitutions, insertions or deletions without deliberately breaking both strands.

In Wilson disease, researchers are attempting to repair a faulty gene so liver cells can handle copper more normally. Unlike treatments that remove a patient's cells, modify them in a laboratory and return them, PM577a delivers its editing components directly to the liver.

Why Wilson disease matters

Wilson disease is estimated to affect about 1 in 30,000 people. ATP7B makes a protein that liver cells use to move excess copper into bile for elimination. Patients take copper-binding drugs to help excrete the metal, or zinc preparations that block its absorption in the intestine. Most must take medication for life, and a liver transplant may be needed if severe liver failure develops, Chosun Biz reported.

According to Prime Medicine, H1069Q accounts for about 30% to 50% of Wilson disease-associated variants in the United States and Europe. The location and type of mutation vary by patient, so one edit will not fit everyone. Prime Medicine is developing a follow-on candidate aimed at R778L, a mutation more frequently reported in East Asian populations. That candidate is still in preclinical development.

What happens next

Initial trial data are expected in 2027, Chosun Biz reported.