With Phase 3 data in hand, Intellia Therapeutics is seeking approval for its in vivo CRISPR gene editing therapy for hereditary angioedema.
Intellia Therapeutics’ in vivo CRISPR-based gene editing therapy, dubbed lonvo-z, reduced hereditary angioedema attacks in a late-stage study, beefing up the asset’s profile as the biotech initiates an approval request with the FDA and gears up for a potential launch next year.
Leerink Partners in a Monday note said the readout from the Phase 3 HAELO study “clears the path for [Intellia’s] transition to a commercial company and positions lonvo-z to disrupt the HAE [hereditary angioedema] market with a functional cure.”
HAELO enrolled 80 patients with HAE and gave them either lonvo-z or placebo. Patients on the in vivo editor saw 87% fewer disease attacks versus placebo over a six-month evaluation period, according to topline results disclosed Monday.
Lonvo-z also aced all key secondary endpoints, including completely eliminating HAE attacks in 62% of patients over six months. In contrast, 11% of those in the placebo group were free of attacks over the same time period.
HAELO is the industry’s first Phase 3 study of an in vivo CRISPR-based gene editor to deliver positive outcomes, Intellia said on Monday. The biotech is up 4.2% to $14.20 before the opening bell.
“We view lonvo-z as a compelling one-time option for patients who will have further choice for prophylaxis,” William Blair wrote in a note to investors on Monday. The analysts also noted that lonvo-z met the firm’s base case of hitting at least an 80% placebo-adjusted HAE attack rate reduction “to be a competitive option as a one-time therapy for patients.”
As for safety, the biotech said lonvo-z had a “favorable” tolerability profile. Most treatment-emergent adverse events were infusion-related side effects or headache and fatigue. There were no serious side effects, and Intellia did not disclose any cases of liver toxicity.
Liver safety emerged as a key question for William Blair, which in a Feb. 26 note pointed to another Intellia asset, nex-z, which is likewise a gene editor based on the CRISPR technology. In October 2025, the FDA pressed pause on two Phase 3 studies of the investigational therapy in transthyretin amyloidosis (ATTR) after one patient developed grade 4 elevations in liver enzymes. This patient died days later.
CEO John Leonard at the time attributed the mortality to “complicating comorbidities,” though it is unclear what these other conditions were. The FDA lifted the hold on next-z last month.
“We are unsure if nex-z liver safety signals may impact . . . lonvo-z, given the similarity in drug design and therapeutic approach,” William Blair wrote in its February note. The analysts at the time said HAELO would be a “pivotal catalyst” for Intellia.
The analyst group did not address safety in its early Monday note, opting to wait for further commentary from Intellia. Leerink, on the other hand, called lonvo-z’s safety profile “clean,” with no “platform/technology read-across risk from the ATTR program.”
With HAELO’s positive outcome in hand, Intellia on Monday also kicked off the rolling submission of its biologics license application for lonvo-z. The company expects to complete the package this year, with a potential approval and launch in the first half of 2027. If approved, lonvo-z would become the “world’s first in vivo CRISPR-based gene editing therapy,” Leonard said in a prepared statement.
Lonvo-z is a gene editing therapy that works by reducing levels of the kallikrein protein, a key player in disease cascades that culminate in severe and recurrent inflammation—a hallmark of HAE. Lonvo-z is designed to provide a one-time treatment for HAE, which currently can only be managed through chronic treatment, Intellia said on Monday. Around 1 in 50,000 people worldwide have HAE.
