Intellia Therapeutics (NTLA) Study Update summary

Study design and methodology

• Phase 2 was a double-blind, randomized, placebo-controlled, international, multicenter study enrolling 27 adults with hereditary angioedema (HAE) types I and II, requiring washout of prior prophylaxis before dosing.

• Patients were randomized to receive a single intravenous 25 mg or 50 mg dose of NTLA-2002 or placebo, with primary efficacy measured by monthly angioedema attacks over 16 weeks.

• Attack rate reduction in Phase 2 was measured against placebo, unlike Phase 1, which used each patient's baseline as reference.

• After the 16-week observation, patients could resume prior therapy, and placebo patients were offered NTLA-2002.

• The study included patients with a range of baseline disease severity and prior use of long-term prophylaxis.

Efficacy results

• A single 50 mg dose led to a mean monthly attack rate reduction of 77% (weeks 1–16) and 81% (weeks 5–16) versus placebo, with eight of 11 patients (73%) attack-free through the latest follow-up.

• The 25 mg arm showed a 75–80% reduction in attack rates, with four of 10 patients attack-free.

• The 50 mg dose achieved an 86% mean reduction in plasma kallikrein from baseline at week 16.

• NTLA-2002 produced dose-dependent, durable reductions in plasma kallikrein protein.

• Most reported attacks were internal and based on patient-reported symptoms, with some possibly not true angioedema attacks.

Safety and tolerability

• NTLA-2002 was well tolerated at both dose levels, with no serious adverse events related to the drug; most adverse events were mild or moderate, including headache, fatigue, nasopharyngitis, and infusion-related reactions.

• No clinically significant laboratory abnormalities were observed, and no patients discontinued due to adverse events.

• No clear correlation was observed between safety events and efficacy response.

• No serious adverse events related to NTLA-2002 were reported; one serious event in placebo arm attributed to underlying HAE.

• All treatment-emergent adverse events resolved without sequelae.