Phase 3 trial of NTLA-2002, gene-editing therapy, possible in 2024
Deep cuts in monthly swelling attacks, safety being seen in Phase 1/2 study
A single dose of the gene-editing therapy NTLA-2002 led to significant reductions in the number of swelling attacks among people with hereditary angioedema (HAE) in a Phase 2 clinical trial.
NTLA-2002’s developer, Intellia Therapeutics, announced the study met its main goal, demonstrating that the investigative gene therapy was better than a placebo at reducing the number of monthly swelling attacks. All secondary trial goals, which included assessing changes in the levels of disease biomarkers and in the number of swelling attacks requiring on-demand treatment, also were met.
The company now is proceeding with plans for a Phase 3 clinical trial of NTLA-2002 that is expected to start later this year, pending feedback from regulatory authorities.
Ongoing Phase 1/2 trial meets primary and secondary efficacy goals
“We are delighted to report the Phase 2 study of NTLA-2002 met its primary efficacy and all secondary endpoints at both dose levels and, importantly, provided clear support for advancing the 50 mg dose into the pivotal Phase 3 trial in patients with hereditary angioedema,” John Leonard, MD, Intellia’s president and CEO, said in a company press release.
HAE is due to high levels of a signaling molecule called bradykinin, which drive the swelling attacks that characterize the disease. Bradykinin’s production is mediated by an enzyme called kallikrein.
NTLA-2002 uses the gene-editing technology CRISPR to inactivate a gene that encodes prekallikrein, a kallikrein precursor. By knocking out this gene, the therapy aims to lower the levels and activity of the kallikrein enzyme, thereby reducing bradykinin production and helping to prevent swelling attacks.
The therapy is being tested in an ongoing Phase 1/2 clinical trial (NCT05120830) that has enrolled 37 adults with HAE. Intellia recently announced long-term data from the study’s Phase 1 portion, in which 10 patients were given a single infusion of NTLA-2002 at one of three doses. The rates of monthly swelling attacks decreased by a mean of 98% after nearly two years of follow-up, with most patients being completely free from swelling attacks after treatment.
Its Phase 2 part started dosing last year, with patients given a single infusion of NTLA-2002 at one of two doses (25 or 50 mg) or a placebo. According to Intellia, both doses of NTLA-2002 led to “deep reductions” in the number of swelling attacks, with no new safety issues identified, over a 16-week primary observation period. The company didn’t provide further details, noting that in-depth findings will be presented at a future scientific meeting.
‘Clear path’ seen for a Phase 3 trial of NTLA-2002 in the ‘coming months’
“We look forward to presenting the detailed Phase 2 results at a medical meeting in the fourth quarter as we continue to advance what we believe could be a functional cure for hereditary angioedema,” Leonard said.
Based on Phase 1/2 study findings, Intellia has selected the 50 mg dose of NTLA-2002 for further testing in a pivotal Phase 3 clinical trial. The company said this dose led to greater reductions in kallikrein levels, and more patients given this dose were free of attacks.
Intellia also reported having completed an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA), where plans for an upcoming Phase 3 trial of NTLA-2002 were discussed. This trial, the company added, is on track to start later this year subject to further regulatory feedback.
“Based on these positive results and our recent successful end-of-Phase 2 meeting with the FDA, we see a clear path to initiating the Phase 3 trial in the coming months,” Leonard said.
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