First HAE patient dosed in Phase 3 trial of NTLA-2002 gene therapy
HAELO study part of developer’s ‘final lap' before request for approval
The first patient has been dosed in a Phase 3 clinical trial testing NTLA-2002, Intellia Therapeutics’ gene-editing treatment candidate for hereditary angioedema (HAE).
The trial, called HAELO (NCT06634420), is expected to enroll an estimated 60 adults with HAE types 1 or 2; it’s recruiting participants at five locations in the U.S. and one in Canada. Launched last fall, the study is expected to conclude in 2027.
In the meantime, however, Intellia is planning to submit a biologics license application to the U.S. Food and Drug Administration in 2026 seeking approval of NTLA-2002 for HAE. If approved, the therapy is expected to enter the U.S. market in 2027.
“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, Intellia’s president and CEO, said in a company press release.
According to Joshua Jacobs, MD, medical director at Allergy & Asthma Clinical Research in Walnut Creek, California, one of the trial sites, NTLA-2002 is “a new generation of therapy that could potentially provide patients with lifelong relief from the primary symptoms of HAE.”
“We are excited to have treated the first patient in the U.S.,” Jacobs said.
Phase 3 trial still enrolling HAE patients in US, Canada
The swelling attacks that characterize HAE are driven by elevated levels of a signaling molecule called bradykinin. Its production is regulated by an enzyme called kallikrein.
An experimental, one-time, gene-editing therapy, NTLA-2002 uses CRISPR/Cas9 technology to deactivate the gene that encodes prekallikrein, a precursor to the kallikrein enzyme. By reducing kallikrein production and activity, NTLA-2002 is expected to decrease bradykinin levels and prevent the swelling episodes characteristic of HAE.
A Phase 1/2 clinical trial (NCT05120830) is now evaluating NTLA-2002 in 37 adults with HAE. In the Phase 1 portion, 10 participants received a single dose of NTLA-2002 at one of three dose levels.
Data after almost two years of follow-up showed the gene-editing therapy led to a mean 98% reduction in monthly swelling attacks, with most patients experiencing no swelling episodes.
With the promising [NTLA-2002] data we’ve presented thus far, we believe patients could achieve independence from both HAE attacks and medications required to treat this disease.
In the Phase 2 portion, 27 patients received a single infusion of NTLA-2002 at a dose of either 25 mg or 50 mg, or a placebo. During a primary observation period of approximately 16 weeks, or nearly four months, both treatment doses substantially lessened the frequency of swelling attacks, with no new safety concerns identified.
Leonard said Intellia will present longer-term data from that Phase 1/2 study later this year, which he says “[highlights] the durability of effect of NTLA-2002” treatment.
“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, Leonard said.
In HAELO, participants are being randomly assigned to receive a single 50 mg infusion of NTLA-2002 or a placebo. The trial’s main goal is to evaluate the therapy’s efficacy in reducing the number of HAE attacks from week five through week 28, or over a span of about six months.
Additional goals include assessing the proportion of participants who are free of attacks, as well as changes in quality of life. The study also will evaluate the percentage of patients who are attack-free and no longer require on-demand or preventive treatment for up to two years.
Participants initially treated with the placebo will have the option to receive NTLA-2002 at week 28. The goal is to assess the impact of treatment on the number of swelling attacks occurring from week 33 for up to two years.
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