Intellia's CRISPR Gene Editor Reduces Hereditary Angioedema Attacks by 81% in Phase II Trial

Intellia Therapeutics revealed promising Phase II results for its CRISPR treatment NTLA-2002, aimed at hereditary angioedema (HAE). This disorder is marked by recurrent and severe swelling episodes. The company's data, which will be presented at the 2024 Scientific Meeting of the American College of Allergy, Asthma & Immunology in Boston, highlights a significant decrease in monthly attack rates among patients treated with NTLA-2002.

The study tested two dosage levels of NTLA-2002: a 25-mg dose and a 50-mg dose. Patients receiving a one-time 25-mg dose saw an 80% reduction in monthly attacks from weeks five to 16 of the follow-up period, while those on the 50-mg dose experienced an 81% reduction in the same timeframe. When considering the broader observation period from weeks one through 16, the 25-mg dose resulted in a 75% decrease in attack rates, and the 50-mg dose achieved a 77% decrease.

Moreover, the higher 50-mg dose produced a complete response in eight out of eleven patients, meaning they had no attacks at all during the 16-week observation period. This response was sustained through the latest follow-up at a median of eight months. In the 25-mg group, four of the ten patients reached a complete response, whereas none of the placebo group participants did.

In terms of safety, both doses were well-tolerated. The most frequently reported side effects included headaches, fatigue, and nasopharyngitis. There were no serious toxicities, though one patient in the placebo arm experienced a severe grade 4 tongue edema that affected breathing. No significant laboratory abnormalities were observed.

John Leonard, CEO of Intellia, expressed strong optimism about these findings, seeing them as evidence of the potential for NTLA-2002 to serve as a functional cure for HAE. He emphasized that these results could change the treatment landscape for patients with this condition. Intellia plans to advance the 50-mg dose of NTLA-2002 into late-stage development, with the Phase III HEALO study already underway.

Analysts have reacted positively but with caution to these results. Jefferies analyst Maury Raycroft noted the "unprecedented complete response rate" demonstrated by NTLA-2002, suggesting that the one-time dosing profile is a significant advantage over other ongoing programs, potentially offering a functional cure for HAE. However, investor reaction was mixed, as Intellia's shares fell by 9% in premarket trading after the data release. This decline was attributed by Raycroft to an "overreaction" from investors who had expected even greater reductions in monthly attack rates based on earlier Phase I data.

Additionally, competition in the HAE treatment space may have impacted investor sentiment. Truist Securities analyst Joon Lee highlighted competitive data from Pharvaris, which reported a 93% reduction in monthly attack rates with its oral daily pill. Despite this competition, William Blair analyst Myles Minter remains optimistic about NTLA-2002's potential in HAE, given the significant response rates achieved. Minter acknowledged that the HAE treatment landscape is highly competitive, with several existing treatment options and new therapies on the horizon.

In summary, Intellia Therapeutics' NTLA-2002 shows considerable promise as a treatment for hereditary angioedema, with the potential for a one-time dosing regimen to offer a functional cure. However, investor confidence remains tempered by high expectations and competitive pressures within the HAE treatment market.