FDA Approves Prime Medicine's Gene Editing Trial

Prime Medicine has received approval from the FDA to initiate a study on a novel drug candidate utilizing its prime editing technology, marking a significant milestone as it is the first human application of this genetic engineering approach. This technology, which was introduced in 2019, is considered superior to CRISPR/Cas9 and base editors due to its ability to make precise genetic alterations without inducing double-strand breaks, which are associated with potential carcinogenic risks.
The company is pioneering the use of prime editing to combat various diseases, and the FDA's green light to test PM359 ex vivo for chronic granulomatous disease (CGD) signifies a step towards the first-ever human study employing this technique. CGD is a condition characterized by mutations in the p47phox protein, leading to recurrent and severe infections that are challenging to treat. Although allogeneic hematopoietic stem cell transplantation can be curative, it is not widely accessible, and patients face the risk of graft-versus-host disease and transplant failure.
Prime Medicine's PM359 is created by using prime editing to fix the patient's hematopoietic stem cells ex vivo. Preclinical studies have shown that these corrected cells can successfully repopulate the bone marrow and restore the enzyme deficient in CGD. The company plans to conduct a Phase I/II trial in three stages, beginning with adults over 18 with stable disease, and subsequently including younger patients and those with active infections or severe inflammation. The trial will monitor early signs of immune function recovery, with the first clinical results expected to be released in 2025.
Prime Medicine, like other CRISPR-focused biotechs, has chosen an ex vivo approach for its initial platform application but has a broader pipeline that includes in vivo therapies. In vivo editing presents its own set of risks, as it involves altering DNA within the human body, which could result in unintended, long-term health consequences. The company is also developing methods to deliver prime editors using lipid nanoparticles (LNP) and adeno-associated virus vectors, targeting a variety of diseases affecting the liver, eyes, nervous system, and other organs. Prime Medicine is on course to begin human studies of an LNP-based liver therapy by the end of 2025, following the completion of IND-enabling activities later this year.