Intellia’s CRISPR Gene Editing Therapy NTLA-2002 Reduces Hereditary Angioedema Attack Rate in Long-Term Follow-Up Data


There was a 98% (2.7% SD) mean reduction in monthly HAE attack rate through the patients’ most recent assessment.

Intellia Therapeutics’ NTLA-2002, an investigational CRISPR/Cas9-based gene-editing therapy that is delivered systemically as a single-dose and is being evaluated in a phase 1/2 clinical trial (NCT05120830) for the treatment of hereditary angioedema (HAE), significantly reduced monthly HAE attacks, according to long-term follow-up data presented at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024, held May31-June 3 in Valencia, Spain.1

Among the 10 patients that have been treated in the phase 1 portion of the trial, who have a median follow-up time of 20.1 months, there was a 98% (2.7% SD) mean reduction in monthly HAE attack rate through the patients’ most recent assessment. In the same timeframe, for attacks requiring on-demand treatment, there was a 97% (3.5% SD) mean reduction, and for moderate-to-severe attacks, there was 99% (1.3% SD) mean reduction. Furthermore, after the primary observation period, which lasted from weeks 1 to 16 posttreatment, the mean monthly HAE attack rate for the patients was .01 (SD .02). It was also noted that 8 of the 10 treated patients have been free of any HAE attacks since the primary observation period finished and that none of the patients who withdrew from other long-term prophylaxis while on-study have resumed use of that prophylaxis. For the 2 patients who were not HAE-free after the primary observation period, Intellia noted that 1 patient experienced a mild attack that did not necessitate treatment and the other patient experienced an attack of moderate severity. The mean reduction in monthly HAE attack rate for these 2 patients was 97% as of their latest follow-up.

The study also measured levels of kallikrein in plasma.1 For the 3 patients who were treated with 25mg of NTLA-2002, there was a 60% mean decrease from baseline kallikrein in the plasma at 88 weeks on-study. For the 4 patients who were treated with 50 mg of NTLA-2002, there was an 88% mean decrease from baseline at 72 weeks on-study. For the 3 patients who received a 75 mg dose of NTLA-2002, there was a 95% mean decrease from baseline at 88 weeks on-study.

In terms of safety, no treatment-emergent adverse events (TEAEs) of grade 3 or greater and no serious TEAEs had been reported as of the patients’ most recent follow-up assessments. There were also no AEs of special interest that were not infusion-related reactions, no grade 2 or higher liver enzyme elevations or platelet count decreases, and shifts in coagulation parameters that were deemed clinically significant. Infusion-related reactions occurred in 7 patients, COVID-19 in 6 patients, fatigue in 6 patients, upper respiratory tract infection in 5 patients, myalgia in 3 patients, abdominal discomfort in 2 patients, headache in 2 patients, and viral upper respiratory tract infection in 2 patients.

Intellia indicated that the phase 2 portion of the study has completed enrollment of patients. The company anticipates announcing results from the phase 2 portion within 2024. Intellia also intends to carry out a pivotal phase 3 clinical trial for NTLA-2002, pending regulatory feedback.2

“These unprecedented data strengthen our view that NTLA-2002 could be a groundbreaking treatment for people living with hereditary angioedema,” John Leonard, MD, the president and CEO of Intellia Therapeutics, said in a statement.2 “After a single dose of our investigational in vivo CRISPR-based therapy, patients experienced durable elimination of their attacks. We are thrilled to see that the majority of patients have been attack free for over 18 months or longer. These remarkable attack rate reductions have been consistent, even in patients with the most severe symptoms. At the same time, the data from these 10 patients continue to demonstrate a very favorable safety profile. These long-term data provide strong evidence that NTLA-2002 could be a one-time, potential functional cure for this debilitating and life-threatening disease.”

NTLA-2002 was previously granted regenerative medicine advanced therapy designation by the FDA in March 2023.3 It also previously received orphan drug designation from the FDA in September 2022.4

1. Longhurst H, Gurugama P, Lindsay K, et al. CRISPR-based gene editing of KLKB1 resulted in long-term plasma kallikrein protein reduction and decreased attack rate in patients with hereditary angioedema. Presented at: EAACI Congress 2024, held May 31-June 3, in Valencia, Spain.
2. Intellia Therapeutics announces positive long-term data from ongoing phase 1 study of NTLA-2002, an investigational in vivo CRISPR gene editing treatment for hereditary angioedema (HAE). News release. Intellia Therapeutics, Inc. June 2, 2024. Accessed June 14, 2024.
3. Intellia Therapeutics anounces FDA Regenerative Medicine Advanced Therapy (RMAT) designation granted to NTLA-2002 for the treatment of hereditary angioedema. News release. Intellia Therapeutics. March 21, 2023. Accessed June 14, 2024.
4. Intellia Therapeutics receives U.S. FDA orphan drug designation for NTLA-2002, an investigational CRISPR therapy for the treatment of hereditary angioedema. News release. Intellia Therapeutics. September 1, 2022. Accessed June 14, 2024.
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