Prime editing comes of age as FDA clears human trials

Prime Medicine has been given the go-ahead by the FDA for the first human trial of its prime editing technology, which promises to deliver one-shot therapies for a range of severe genetic diseases.

According to the Cambridge, Massachusetts biotech, the US regulator has cleared an investigational new drug (IND) application for ex vivo use of its Prime Editor platform to correct a mutation associated with chronic granulomatous disease (CGD), which leaves patients vulnerable to recurrent life-threatening infections and severe inflammation.

The planned phase 1/2 trial will see Prime Medicine’s PM359 candidate used to modify haematopoietic stem cells (HSCs) taken from CGD patients outside the body, to edit out a mutation in the gene coding for the NADPH oxidase complex that prevents phagocytic cells of the immune system from destroying microorganisms.

At the moment, patients with CGD – which normally manifests in childhood – often have to take near-constant doses of antibiotics to protect them from infections, as well as high-dose steroids to reduce inflammation, unless they are lucky enough to have a matched donor for a bone marrow transplant.

PM359 will be tested in adults with stable disease in the phase 1 portion of the trial and, if all looks okay with safety and gene expression data, it will then enrol adults and children with active infection and/or severe inflammation.

Prime Medicine’s ‘search-and-replace’ genome editing technology – initially identified by gene-editing pioneers David Liu and Andrew Anzalone at the Broad Institute – has already been shown to work in non-human primates, and moving it into clinical trials is a major step forward for the company.

Prime editing aims to improve on the CRISPR-Cas9 gene-editing approach by allowing changes to be made to DNA without breaking the double helix or using donor DNA. It is more broadly applicable than CRISPR-Cas9, according to the biotech, which says it could be used to target more than 90% of known disease-causing mutations.

“We are thrilled to achieve this important milestone for our first product candidate, PM359, which represents the first-ever IND clearance for a Prime Editor product candidate and a significant advancement in the field of next-generation gene editing,” said Keith Gottesdiener, Prime Medicine’s chief executive.

“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,” he added. Data from the study will start to emerge next year, according to the company.

The approval to start the trial comes shortly after Prime Medicine completed an upscaled $161 million public offering that will help fund the CGD trial and other candidates in its pipeline, including candidates for eye disease retinitis pigmentosa, liver diseases, and Friedreich’s ataxia. It finished 2023 with cash reserves of $135 million, down from $307 million at end-2022.

Before the end of this year, Prime Medicine is hoping to have IND-enabling activities in place for its first liver and ocular disease programmes.