New FDA and EMA Designations for Two Gene-Editing Candidate Therapies

Editas awarded RMAT designation for EDIT-301

Earlier this week, Editas Medicine announced in a press release that it has been granted the FDA's Regenerative Medicine Advanced Therapy (RMAT) designation for EDIT-301, for the treatment of severe sickle cell disease.

EDIT-301 is an autologous (donor-derived) CRISPR-edited cell therapy candidate that is currently being evaluated in the RUBY Phase 1/2 trial in 40 adult participants between the ages of 18 and 50 years. The single-arm, open-label, multicenter trial is actively recruiting, and the overall goal is to evaluate the efficacy, safety and tolerability of EDIT-301 in adults with severe SCD.

EDIT-301 is the first experimental medicine developed using CRISPR-Cas12a gene-editing technology, and it is specifically edited using a CRISPR-Cas12a ribonucleoprotein to enhance the HBG1/2 promoter region in the beta-globin locus of patient-derived HPSCs. Naturally-occurring HbF-inducing mutations at the HBG1/2 region support the clinical relevance of using gene editing to enhance the HBG1/2 promoter, and this strategy has been shown to increase the red blood cell levels of HbF.

EDIT-301 has already been granted FDA Orphan Drug Designation for the treatment of SCD, and Rare Pediatric Disease Designation for the treatment of SCD in individuals from birth to the age of 18 years.

In June 2023, Editas announced positive initial safety and efficacy data from the first four patients with SCD treated with EDIT-301 in the RUBY trial. You can read more about that, as well as other ongoing gene-editing trials for SCD here.

Intellia gets EMA's Priority Medicines (PRIME) Designation for NTLA-2002

Last week, Intellia Therapeutics announced in a press release that the European Medicines Agency (EMA) had awarded a Priority Medicines (or PRIME) designation to its Phase 1/2 gene-editing candidate, NTLA-2002, for the treatment of hereditary angioedema (HAE).

NTLA-2002 is an in vivo CRISPR candidate that is designed to be a single-dose treatment for HAE. The most recent clinical data, released earlier this year from the Phase 1 portion of the ongoing Phase 1/2 trial of NTLA-2002, revealed that across all patients evaluated at their latest follow-up, a single treatment with NTLA-2002 led to a 95% mean reduction in monthly severe inflammatory attacks seen in HAE patients.

HAE is characterised by severe inflammatory attacks with swelling in various organs and tissues. Plasma kallikrein is a protein known to drive multiple inflammatory pathways, including the production of the inflammatory mediator bradykinin, which is overproduced in HAE. Plasma kallikrein inhibition is among the current treatment approaches to HAE.

NTLA-2002 is designed to knock out the target gene kallikrein B1 (KLKB1) in hepatocytes. This gene encodes prekallikrein, a precursor of plasma kallikrein, thus its knockout permanently reduces plasma kallikrein activity and halts the production of bradykinin to prevent HAE attacks.

NTLA-2002 is administered intravenously as a single dose of Cas9 mRNA and gRNA via lipid nanoparticles. Pre-clinical studies demonstrated sustained and therapeutically relevant reduction in plasma kallikrein activity following a single dose in non-human primates.

You can read more about NTLA-2002 and clinical data from the HAE trial so far in a previous clinical trial update here.

For a complete overview of current gene editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.