RMAT Designation Granted to Hereditary Angioedema CRISPR Therapy
Intellia Therapeutics received clearance to enroll patients from the US in the global phase 2 portion of its clinical trial earlier this month.
The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) Designation to Intellia Therapeutics’ CRISPR-based gene-editing therapy NTLA-2002 for the potential treatment of hereditary angioedema (HAE).1
“The RMAT designation is important recognition for our early clinical data. It indicates that a single dose of NTLA-2002 has the potential to address serious unmet medical need for people living with HAE,” John Leonard, MD, president and chief executive officer, Intellia, said in a statement.1 “We look forward to continuing our productive dialogue with the FDA to accelerate the development of NTLA-2002, an investigational in vivo CRISPR-based therapy, with the goal of bringing forth a potentially transformative treatment to patients more quickly.”
NTLA-2002 is an in vivo CRISPR/Cas9-based investigational therapy designed to inactivate the KLKB1 gene and prevent life-threatening swelling attacks in people with HAE. The therapy is currently being evaluated in a phase 1/2 study (NCT05120830) that is enrolling participants from the Netherlands, New Zealand, and the United Kingdom, although Intellia earlier this month received clearance to enroll patients from the US in the global phase 2 portion of the study.2
The study is evaluating 2 dose levels of NTLA-2002 and primary outcome measures include safety and tolerability as measured by incidence and severity of adverse events (AEs) in the phase 1 portion of the trial and the number of HAE attacks per month in the phase 2 portion. Both phases will evaluate secondary outcome measures of change in total plasma kallikrein protein level and plasma and urine concentrations for DMG-PEG2k, LP000001, Cas9 mRNA, and sgRNA.
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“The FDA’s acceptance of our investigational new drug application (IND) to initiate clinical evaluation of NTLA-2002 brings us 1 step closer to introducing a potentially paradigm-shifting treatment for people living with hereditary angioedema,” Leonard said in an earlier statement.2 “The NTLA-2002 IND clearance marks an important milestone for Intellia as we continue ourtrack record of execution as the leader in the genome editing field. We are thrilled to advance the development of NTLA-2002 in the US and are working to rapidly enroll patients in the phase 2 portion of the study. We look forward to presenting additional data from the first-in-human, phase 1 portion of the study later this year.”
The latest data from the study, presented in late 2022, demonstrated a mean 64% plasma kallikrein reduction as of week 32 in 10 evaluable participants, specifically, the 50 mg cohort had a mean 81% plasma kallikrein reduction as of day 22, and the 75 mg cohort had a mean 92% plasma kallikrein reduction as of week 16.3 Additionally, the 50 mg cohort had a 91% mean HAE attack rate reduction from weeks 1 to 16 and an 89% reduction from weeks 5 to 16, while the 75 mg cohort had a 78% mean HAE attack rate reduction from weeks 1 to 16 and an 89% reduction from weeks 5 to 16.
