The FDA has cleared a clinical trial of an ex vivo prime editing candidate in patients with a rare disease, Prime Medicine announced Monday. The technique taps CRISPR technology to rewrite defective genes without breaking DNA double helix strands.
Prime Medicine announced Monday that the FDA has cleared a study of a drug candidate based on its prime editing platform, marking the first time the agency has greenlit the use of the genetic technology in humans.
Advocates of prime editing view the technology as an improvement on CRISPR/Cas9 and base editors. Unveiled in a Nature paper in 2019, the technology was designed to eliminate aspects of CRISPR that can cause health problems. Prime editors make changes without causing double-strand breaks, which can in theory lead to cancer and can make a wide range of edits such as substitutions, insertions and deletions.
Prime Medicine is at the forefront of efforts to use the technology to treat disease. The FDA clearance of an application to test the ex vivo candidate PM359 in chronic granulomatous disease (CGD) positions the biotech to run the first human study of prime editing.
CGD is caused by mutations in the p47phox protein. Patients have recurrent, life-threatening bacterial and fungal infections that are difficult to eradicate. Allogeneic hematopoietic stem cell transplantation can cure the condition but access to the treatment is limited. Patients who do receive transplants are at risk of graft-versus-host disease and graft failure.
Prime Medicine makes PM359 by using prime editors to correct the patient’s own hematopoietic stem cells outside of the body. In preclinical tests, edited cells repopulated the bone marrow and restored the enzyme at the root of the rare disease.
The biotech will evaluate the candidate in three small cohorts in a Phase I/II trial, starting with people aged 18 years and over who have stable disease. Later cohorts will test PM359 in people aged as young as six years and in participants with active infection or severe inflammation. Prime Medicine will track endpoints including early markers of restored immune function and aims to share the first clinical data in 2025.
Like some CRISPR biotechs before it, Prime Medicine has picked an ex vivo application as the first use of its platform but has a pipeline that skews toward in vivo therapies. In vivo editing eliminates the need to remove and re-administer cells but altering DNA inside humans also creates additional risks. Off-target edits could have long-term negative effects on health.
Prime Medicine is developing candidates that use lipid nanoparticles (LNP) and adeno-associated virus vectors to deliver prime editors. The biotech is working on a range of diseases that affect the liver, eye, nervous system and other parts of the body. IND-enabling activities are scheduled to start this year, putting Prime Medicine on track to study a LNP liver candidate in humans around the end of 2025.
Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.
