Prime Medicine has announced groundbreaking clinical data from the first human patient treated with its Prime Editing technology, showing rapid restoration of immune function in a patient with Chronic Granulomatous Disease (CGD). The results mark a significant milestone in genetic medicine, demonstrating the first clinical validation of Prime Editing as a potentially curative approach for genetic disorders.
The preliminary data comes from the first patient dosed in Prime Medicine's ongoing Phase 1/2 clinical trial of PM359, an ex vivo Prime Edited autologous hematopoietic stem cell (HSC) therapy designed to treat p47phox Chronic Granulomatous Disease.
Remarkable Efficacy in First Patient
The adult patient received a single intravenous infusion of PM359, which led to complete restoration of NADPH oxidase activity in 58% of neutrophils by Day 15, increasing to 66% by Day 30. These results significantly exceeded the anticipated minimum threshold of 20% believed necessary for clinical benefit.
"We created prime editing five and a half years ago as a versatile, precise genome editing technology that in principle could correct almost all mutations known to cause genetic diseases," said David Liu, Ph.D., Co-Founder of Prime Medicine and Director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad Institute of MIT and Harvard. "Today's data represent a milestone in medicine, establishing that prime editing in a patient's cells can correct a pathogenic mutation and can change the course of a life-limiting disease."
The patient also experienced notably rapid engraftment following myeloablative conditioning, with confirmed engraftment in neutrophils on Day 14 and in platelets on Day 19. This timeline is approximately twice as fast as what has been reported with other approved gene editing technologies, where median engraftment typically occurs around Days 27 and 35.
Promising Safety Profile
Treatment with PM359 was generally well-tolerated, with an acceptable safety profile. Adverse events were consistent with those typically observed during myeloablative conditioning with busulfan, and no serious adverse events related to PM359 were reported as of the data cutoff.
Mohammed Asmal, M.D., Ph.D., Chief Medical Officer of Prime Medicine, emphasized the dual significance of these results: "For people living with CGD, these results suggest Prime Editing may offer a reprieve from their disease, restoring NADPH oxidase function and, therefore, reducing the risk of acquiring a deadly infection or suffering from inflammation of the lung, liver or bowel."
Understanding Chronic Granulomatous Disease
CGD is a rare inherited hematologic disorder characterized by susceptibility to severe, difficult-to-treat infections and inflammatory complications. The disease is caused by mutations in genes that encode proteins forming the NADPH oxidase complex, an enzyme critical for phagocytic cells, particularly neutrophils, to destroy invasive microorganisms.
The condition affects approximately one in 100,000 to 200,000 births in the United States, with about 25 percent of patients presenting with the p47phox form of the disease targeted by PM359. Most children with CGD are diagnosed within the first three years of life and face recurrent infections from various bacteria, fungi, and mycobacteria that can lead to long-term organ damage and failure.
PM359 is designed specifically to correct the delGT mutation in the NCF1 gene, the most prevalent disease-causing mutation in the p47phox variant of CGD. The therapy has received both rare pediatric drug designation and orphan drug designation from the U.S. Food and Drug Administration.
Strategic Shift in Development Focus
Despite the promising results, Prime Medicine announced it does not plan to independently advance its efforts in CGD. The company is exploring options for continued clinical development of PM359 through external partnerships while ceasing further efforts in X-linked CGD.
Moving forward, Prime Medicine will focus its resources on advancing its in vivo liver franchise, targeting Wilson's Disease and Alpha-1 Antitrypsin Deficiency (AATD). The company will also continue its in vivo Cystic Fibrosis program with support from the Cystic Fibrosis Foundation and its development of Prime Edited CAR-T products for hematology, immunology, and oncology in partnership with Bristol Myers Squibb.
Prime Editing: A Versatile Gene Editing Platform
Prime Editing represents a new approach to genetic modification, designed to make precise edits at specific positions within genes while minimizing unwanted DNA modifications. The technology has the potential to repair almost all types of genetic mutations and work across different tissues, organs, and cell types.
Unlike other gene editing approaches, Prime Editing is designed for precision and versatility, potentially unlocking therapeutic opportunities across thousands of genetic conditions. The platform's modularity may enable rapid and efficient expansion beyond the diseases in Prime Medicine's current pipeline.
Dr. Asmal noted that these initial results "answer key questions about Prime Editors, confirming their potential to be delivered safely and restore normal gene function. This reaffirms our conviction that Prime Editing will be the foundation of a new class of differentiated, one-time genetic therapies."
As the first clinical validation of Prime Editing technology in humans, these results represent a significant advancement in the field of genetic medicine and offer new hope for patients with previously untreatable genetic disorders.
