Intellia is ready to talk 'functional cure' for HAE with interim data in hand for 2nd CRISPR candidate

Intellia Therapeutics has a few more drops of evidence that its second gene editing candidate may offer a functional cure for hereditary angioedema (HAE), a rare inherited disorder that causes rapid swelling all over the body.

The company already revealed interim data from a phase 1/2 study in September showing that NTLA-2002 reduced mean plasma kallikrein by 65% and 92% at 25-mg and 75-mg doses, respectively, at Week 8. Plasma kallikrein is a serine protease that is known to be involved in many processes in the body, including blood coagulation and the classical complement pathway.

Approved medicines for HAE inhibit this mechanism to try to address attacks as they happen or prevent them. Intellia, however, is hoping that NTLA-2002 will provide a one-and-done treatment that will continually reduce kallikrein activity and therefore prevent attacks.

While the data sample is small, Intellia is now reporting that all patients in the 25-mg and 75-mg groups have an ongoing attack-free interval at the latest follow-up. The first three patients have been attack-free for a range of 5.5 months to 10.6 months after one dose. The update was presented at the American College of Allergy, Asthma & Immunology 2022 Annual Scientific Meeting on Saturday.

Reductions and kallikrein have been observed at all dose levels. In the 75-mg arm, the reduction was 92% at Week 16; patients in the 50-mg group had reductions of 81% at Day 22; and the 25-mg cohort saw reductions of 64% at Week 32.

The data for the 75-mg and 25-mg groups are similar to the interim results seen in September, but Intellia said the latest information shows a durability of response. While gene editing has been a much buzzed about new modality, a question has remained as to whether the edit is permanent. Intellia, which is one of the leading gene editing companies with data on the table, is hoping to answer those questions by showing sustained responses like this.

Intellia said this is the second time a candidate has shown deep and consistent protein reduction after a single dose, which reinforces the company’s CRISPR-based gene editing platform.

NTLA-2002 was generally well tolerated, with the majority of adverse events mild, including infusion-related reactions that quickly resolved in a day. Patients have not reported any dose-limiting toxicities, and no grade 3 or higher adverse events have been reported. The data include 10 patients with a cutoff of Sept. 28.

CEO John Leonard, M.D., said the results suggest that NTLA-2002 could be a “functional cure” for HAE. Next up, the company plans to pick two doses to take into the phase 2 dose-expansion portion of the trial starting in the first half of 2023. The phase 2 portion will see an expansion into new countries, including U.S. trial sites.