FDA Clears First Trial of Prime Editing Therapy

Rare Daily Staff

The U.S. Food and Drug Administration has granted clearance to Prime Medicine to begin human clinical trials of an experimental prime editing therapy for the rare, autoimmune condition chronic granulomatous disease, the first in a new class of one-time curative genetic therapies.

The company is developing a proprietary Prime Editing platform that enables precise and efficient gene editing technology designed to make only the right edit at the right position within a gene while minimizing unwanted DNA modifications. Prime editors have the potential to repair almost all types of genetic mutations and work in many different tissues, organs and cell types.

Chronic granulomatous disease (CGD) is a rare inherited hematologic disorder characterized by susceptibility to severe, difficult-to-treat infections, and inflammatory complications. CGD is caused by mutations in any one of the subunits comprising the NADPH oxidase complex, which is required for phagocytic cells, in particular neutrophils, to destroy many invasive microorganisms.

The company’s experimental therapy PM359 targets the p47phox variant of chronic granulomatous disease. PM359 uses autologous hematopoietic stem cells modified ex vivo using prime editors that have been designed to correct a high percentage of cells containing the disease-causing mutation. The FDA has granted PM359 Rare Pediatric Drug and Orphan Drug designations.

The phase 1/2 clinical trial is a multinational, first-in-human trial designed to assess the safety, biological activity and preliminary efficacy of PM359 in adult and pediatric study participants. Initial study participants will be adults with stable disease. If safety and biological activity are demonstrated in this cohort, the study is designed to enroll participants with active infection or severe inflammation as well as adolescent and pediatric participants.

Participants will be followed for safety, including engraftment and reconstitution of the hematopoietic system, early biological markers of restored immune function, and long-term resolution and prevention of infectious and inflammatory complications of CGD. Prime Medicine expects to report initial clinical data from the study in 2025.

“Based on data from our preclinical studies, we believe PM359 has the potential to sufficiently correct a prevalent disease-causing mutation of CGD, leading to amelioration of disease for these patients,” said Keith Gottesdiener, president and CEO of Prime Medicine.

Photo: Keith Gottesdiener, president and CEO of Prime Medicine