First Patient Dosed in Phase 3 Trial for Intellia Therapeutics’ Hereditary Angioedema Gene Editing Therapy NTLA-2002

John Leonard, MD
Credit: Intellia

The first patient has been dosed in Intellia Therapeutics’ pivotal phase 3 HAELO clinical trial (NCT06634420) evaluating NTLA-2002, an investigational CRISPR/Cas9-based gene-editing therapy that is delivered systemically as a single-dose, for the treatment of hereditary angioedema (HAE).¹

HAELO takes the form of a double-blind, placebo-controlled study, and will randomly assign participants in a 2:1 ratio to receive either a 50mg dose of NTLA-2002 or placebo. The trial is expected to enroll 60 patients in total, and includes adults with both type 1 and type 2 HAE. Participants who are assigned to the placebo group may cross over to receive the gene-editing therapy at 28 weeks posttreatment. The number of HAE attacks and the number of patients who are attack-free from weeks 5 through 28 posttreatment will serve as key end points for the study. HAELO is currently recruiting patients at sites in Arizona, California, Colorado, and Ohio in the United States and at a site in Ontario, Canada. Intellia anticipates that enrollment in the study will be finished in the second half of this year.

In light of the initiation of dosing in HAELO, Intellia has announced that it expects to put a biologics license application (BLA) in front of the FDA next year and to potentially launch the product commercially in 2027, pending approval of the BLA. NTLA-2002 is also currently being evaluated in an ongoing phase 1/2 clinical trial (NCT05120830) for adults with HAE, which launched on December 10, 2021. NTLA-2002 is a CRISPR/Cas9-based, in vivo genome editing therapy intended to inactivate the kallikrein B1 (KLKB1) gene to reduce plasma kallikrein protein activity and prevent HAE attacks.

“We are pleased to have initiated dosing in the HAELO phase 3 study as we are in our final lap of clinical development for NTLA-2002,” John Leonard, MD, the president and chief executive officer of Intellia, said in a statement.¹ “With the promising data we’ve presented thus far, we believe patients could achieve independence from both HAE attacks and medications required to treat this disease. We look forward to presenting longer-term data from the ongoing phase 1/2 study later this year highlighting the durability of effect of NTLA-2002.”

Data from the phase 1/2 study were recently reported at the 2024 American College of Allergy, Asthma & Immunology Scientific Meeting, held October 24 to 28, in Boston, Massachusetts.² Participants in the trial received either a single dose of 25 mg of NTLA-2002, a single dose of 50 mg of NTLA-2002, or a placebo. As of the April 4, 2024, data cutoff, monthly HAE attacks for patients who received the 50 mg dose were reduced by 77% in comparison to the placebo group for weeks 1 to 16 posttreatment and by 81% during weeks 5 to 16 posttreatment. Notably, 8 of the 11 patients who received the pivotal 50 mg dose of NTLA-2002 were completely free of HAE attacks during the 16 week observation period and beyond, with a median follow-up time of 8 months. Furthermore, these 8 patients did not need any additional treatment during this period.

“These positive NTLA-2002 phase 2 results underscore the tremendous potential of our in vivo CRISPR gene editing therapy to be a functional cure and redefine the treatment paradigm for HAE,” Leonard said in an October 2024 statement.² “The phase 2 data demonstrated that a majority of patients in the 50 mg arm experienced a complete response—no attacks at all and no further treatment needed—after a one-time infusion of NTLA-2002 through the latest follow-up, consistent with the long-term phase 1 data. We are highly encouraged by these results, which we believe sets NTLA-2002 apart from other prophylaxis treatments. What was previously an unimaginable potential to be free of chronic therapy is one step closer to becoming a reality for the HAE community.”

REFERENCES
1. Intellia Therapeutics announces first patient dosed in the HAELO phase 3 study of NTLA-2002, an investigational in vivo CRISPR gene editing treatment for hereditary angioedema. News release. Intellia Therapeutics, Inc. January 22, 2025. Accessed January 23, 2025. https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-announces-first-patient-dosed-haelo-phase
2. Intellia presents positive results from the phase 2 study of NTLA-2002, an investigational in vivo CRISPR gene editing treatment for hereditary angioedema (HAE). News release. Intellia Therapeutics, Inc. October 24, 2024. Accessed January 23, 2025. https://ir.intelliatx.com/news-releases/news-release-details/intellia-presents-positive-results-phase-2-study-ntla-2002