The first 3 patients dosed have been attack-free for up to 10.5 months.
Intellia Therapeutics’ CRISPR-based therapy NTLA-2002 has continued to show efficacy in hereditary angioedema (HAE) in updated data froma phase 1/2 study (NCT05120830) presented at the American College of Allergy, Asthma & Immunology (ACAAI) 2022 Annual Scientific Meeting, held November 10 – 14 in Louisville, Kentucky.
“We see early evidence that our one-time CRISPR-based investigational therapy may offer patients suffering from hereditary angioedema a functional cure for their disease,” John Leonard, MD, president and chief executive officer, Intellia Therapeutics, said in a statement. “Based on the extended data across multiple dose cohorts, we are strongly encouraged that all patients who received a single dose of NTLA-2002 subsequently became attack-free. In the patients with the longest follow-up to date, their attack-free interval has been maintained 5 to 10 months from their last attack. Importantly, the safety data from all 10 patients are highly encouraging, further supporting NTLA-2002’s potential to change the future HAE treatment paradigm.
The data presented, updated as of September 28, 2022, were from 10 participants with HAE from the dose-escalation phase 1 portion of the study. Participants received single doses of 25 mg (n = 3), 50 mg (n = 4), or 75 mg (n = 3) of NTLA-2002 via intravenous infusion. At latest follow-up, the 25 mg cohort had a mean 4% plasma kallikrein reduction as of week 32, 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.
Investigators also assessed HAE attack rates beginning at the end of the pre-specified 16-week primary observation period. The 25 mg cohort, which had a baseline attack rate of 1.1 to 7.2 attacks per month, has been attack free for 5.5 to 10.6 months. This cohort had a 91% mean HAE attack rate reduction from weeks 1 to 16 and an 89% reduction from weeks 5 to 16. The 75 mg cohort, which had a baseline attack rate of 4.0 to 5.9 attacks per month, has been attack-free for 2.3 to 4.2 months, and had a 78% mean HAE attack rate reduction from weeks 1 to 16 and an 89% reduction from weeks 5 to 16.
In terms of safety, NTLA-2002 was well-tolerated, with mostly mild adverse events (AEs). AEs were mostly grade 1 infusion-related reactions which resolved within 1 day. There were no dose-limiting toxicities, no serious AEs, or no clinically significant laboratory abnormalities observed.
“As the second clinical program from our in vivo pipeline to demonstrate deep and consistent protein reduction following a one-time administration, the latest interim data further reinforce the enormous potential of our modular CRISPR genome editing platform to treat a host of genetic diseases,” Leonard added.
Intellia plans to evaluate 2 additional doses of NTLA-2002 in the dose-expansion, phase 2, placebo-controlled portion of the study, which is expected to begin in the first half of 2023. The study will expand to more US and international sites.