Intellia’s CRISPR Gene Editing Therapy NTLA-2002 Appears to Eliminate Hereditary Angioedema Attacks in Some Patients Following One-Time Treatment
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.
Intellia Therapeutics’ NTLA-2002, an investigational CRISPR/Cas9-based gene-editing therapy that is delivered systemically as a single-dose and is being evaluated in a phase 1/2 clinical trial (NCT05120830) for the treatment of hereditary angioedema (HAE), has eliminated HAE attacks in some patients through their most recent follow-up, according to data the company is presenting at the 2024 American College of Allergy, Asthma & Immunology (ACAAI) Scientific Meeting, held October 24 to 28, in Boston, Massachusetts.1
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. For the patients who received the 25 mg dose, HAE attacked were reduced by 75% in comparison to the placebo group for weeks 1 to 16 posttreatment and by 80% during weeks 5 to 16 posttreatment. Furthermore, Intellia noted that 8 of the 11 patients who received the 50 mg dose of the therapy achieved a complete response—defined as experiencing no HAE attacks at all during the 16 week observation period and beyond—with a median follow-up time of 8 months, during which no additional treatment was necessitated. On the other hand, complete responses were achieved by just 4 of 10 patients who received the 25 mg dose, and there were 0 complete responses in the placebo group. In addition, at 16 weeks posttreatment, the patients in the 50 mg group showed an 86% mean decrease in kallikrein protein levels from baseline, while patients in the 25 mg group showed a 55% reduction.
“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,” John Leonard, MD, the president and chief executive officer of Intellia, said in a statement.1 “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.”
In terms of safety, the gene-editing therapy was characterized as “well-tolerated”. No serious adverse events (SAEs) occurred during the study, excepting a single grade 4 case of edema of the tongue with breathing impairment that occurred in 1 patient in the placebo group and that was deemed to have been caused by the disease itself. All other AEs were grade 1 to 2, with the most common being headache, fatigue, and nasopharyngitis. There were no clinically significant laboratory abnormalities reported.
“Approved HAE therapies can reduce, but frequently do not eliminate all angioedema attacks and require chronic administration, resulting in a significant treatment burden and a major impact on the quality of life for people living with HAE,” lead principal investigator Danny Cohn, MD, PhD, an internist in the Department of Vascular Medicine at Amsterdam University Medical Center, added to the statement.1 “These NTLA-2002 phase 2 data are remarkable, showing this investigational therapy could permanently stop swelling attacks with a single infusion. I am optimistic that NTLA-2002 will change the way we treat HAE and put an end to the need for a lifetime of chronic treatment.”
Intellia also announced that it will utilize the 50 mg dose in the pivotal phase 3 HAELO clinical trial (NCT06634420). Screening activities for HAELO are underway.
These data build upon findings reported earlier this year at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024, held May 31 to June 3 in Valencia, Spain.2 At the time, the company noted that for the 2 patients who were not HAE-free after the primary observation period, 1 patient experienced a mild attack that did not necessitate treatment and the other patient experienced an attack of moderate severity.
NTLA-2002 was previously granted regenerative medicine advanced therapy designation by the FDA in March 2023.3 It also previously received orphan drug designation from the FDA in September 2022.4
