Intellia links in vivo CRISPR therapy to 81% drop in HAE attacks in phase 2

Intellia Therapeutics has taken another step toward its goal of winning the first approval for an in vivo CRISPR therapy, linking its hereditary angioedema (HAE) prospect to an 81% reduction in monthly attacks in a phase 2 trial.

The biotech shared phase 1 data on the candidate, NTLA-2002, in June. That trial, which administered a single dose of NTLA-2002 to 10 patients, tracked a 90% reduction in attacks from weeks 1 to 16. The rate of reduction rose to 92% when limiting the analysis to weeks 5 to 16. The data provided early validation of Intellia’s goal of developing a one-time therapy that allows people with HAE to live healthy lives.

Intellia’s phase 2 trial provided a tougher test of that goal. Investigators randomized 27 people to receive either 25 mg or 50 mg of NTLA-2002 or placebo. From weeks 1 to 16, Intellia tracked placebo-adjusted drops in mean monthly attacks of 75% and 77%, respectively, on the low and high dose. The reduction rates rose to 80% and 81%, respectively, when looking at attacks from weeks 5 to 16 of the trial.

Data on the 50-mg dose, which Intellia had already selected for phase 3, are most relevant for Intellia’s hopes of filing for approval in 2026. To realize that plan, the biotech will need to validate the efficacy of the 50-mg dose in the larger, longer phase 3 trial that is scheduled to start this year.

Eight of the 11 patients who received 50 mg of NTLA-2002 were completely attack-free through to the latest follow-up, which tracked patients for a median of eight months. Four of the 10 people on 25 mg of NTLA-2002 were attack-free. Nobody on placebo was free from attacks.

The potential for NTLA-2002 to eliminate attacks and the need for further treatment in most people is central to the biotech’s pitch for its CRISPR therapy. HAE attacks can be fatal, but, between those episodes, people can live normal, healthy lives. Existing options for preventing attacks include BioCryst Orladeyo and Takeda’s Takhzyro. Orladeyo is taken once a day. Takhzyro is used every two to four weeks.

Ionis Pharmaceuticals is developing a drug candidate that is used every four weeks. In a phase 3 trial, the biotech linked the antisense molecule to an 81% drop in the monthly rate of swelling attacks. Intellia is betting there is a market for a therapy with a similar level of efficacy from a single dose. It remains to be seen how payers, physicians and patients weigh the trade-offs between one-time and ongoing therapies.

Investors' initial reaction to the data were, however, not great, with shares down around 10% early Thursday morning on the data drop.  

Given the novelty of NTLA-2002, safety will be a key question for patients considering the therapy. The phase 2 data came in clean, with Intellia reporting no serious adverse events nor clinically significant lab abnormalities. One patient had grade 4 swelling of the tongue with breathing impairment, but that was attributed to their underlying HAE.