HAELO Phase 3: Lonvo-z Secondary Endpoints, QoL Data Detailed at EAACI

Lonvoguran ziclumeran (lonvo-z; Intellia Therapeutics), a one-time in vivo CRISPR gene-editing therapy for hereditary angioedema (HAE), continued to demonstrate compelling efficacy across secondary endpoints in the phase 3 HAELO trial. The team presented new HAELO data in a late-breaking oral session at the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2026 in Istanbul and simultaneously published it in the New England Journal of Medicine.1

In an interview with HCPLive following the meeting, lead investigator Aleena Banerji, MD, professor at Harvard Medical School and director of clinical care at the Center for Drug and Vaccine Allergy at Massachusetts General Hospital, said the secondary endpoint data exceeded her expectations despite entering phase 3 with cautious optimism.

“Going into any phase 3 study [is] unpredictable [in terms of] what the efficacy is going to be,” Banerji said. “It was very exciting to see that not only did the data match what was being seen in the prior phase 1 and phase 2 study, but it really exceeded expectations."

Secondary Endpoints and HAE Attack Reductions

As previously reported, HAELO met its primary endpoint with an 87% reduction in mean monthly attacks in the lonvo-z arm versus placebo during the efficacy evaluation period from weeks 5 to 28.2 The newly disclosed secondary data built further on that result.

The monthly rate of moderate and severe attacks was reduced by 91% in patients receiving lonvo-z compared with placebo (0.11 vs. 1.23; P <.0001), and the monthly rate of attacks requiring on-demand treatment fell by 89% (0.19 vs. 1.79; P <.0001).1

Banerji called the absence of non-responders a particularly meaningful finding. Patient-level data demonstrated that all patients in the lonvo-z arm experienced attack-rate reductions from baseline during weeks 5 to 28.

"It's rare that we see that when you look across a lot of other trials or even outside of hereditary angioedema," Banerji said.

Quality of Life Improvements With Lonvo-Z

Patients receiving lonvo-z experienced a mean improvement of 17.04 points in the Angioedema Quality of Life (AE-QoL) total score compared with approximately 6.5 points in the placebo arm, a difference that exceeded the 6-point threshold considered clinically meaningful.1

Banerji said that threshold context matters when interpreting the magnitude of that gain. “A 17-point change far exceeds what we believe is clinically meaningful," she noted. Patients in the trial reported being able to think differently about work, school, and travel—including activities like taking a cruise—without organizing their lives around the fear of an impending attack.

"It's the constant fear of that next attack and when it's going to occur," Banerji said. "Being able to change that and seeing this significant improvement in quality-of-life matching what we're seeing with efficacy is really promising for the real world."

Enrollment Across the Treatment Spectrum

The HAELO population included patients across a range of prior treatment histories, from those naive to long-term prophylaxis (LTP) to those who were attack-free on existing regimens. Notably, 20% of enrolled patients reported having complete disease control as their best response to prior long-term prophylaxis therapies and yet still chose to enroll.1

Banerji addressed why patients already well-controlled on LTP would pursue an investigational gene editing therapy: the burden of treatment itself, including insurance approvals, supply management, and injection schedules.

“Just because they're doing well on long-term prophylaxis in terms of not having attacks or feeling that they are attack-free isn't the only aspect of hereditary angioedema,” she said.

HAELO Safety Findings

All treatment-emergent adverse events (TEAEs) reported in the lonvo-z arm were mild or moderate, with no serious adverse events observed. The most common TEAEs exceeding placebo rates were infusion-related reactions, headache, fatigue, back pain, and upper respiratory tract infection.1

Banerji said the safety monitoring focus centered on liver function, given the hepatic targeting mechanism of an in vivo CRISPR therapy. No transient or persistent elevations in liver function tests were observed, and infusion reactions resolved without interrupting dosing in any patient.

Kallikrein Kinetics and Durability

Plasma kallikrein levels decreased substantially by the first measurement at day 15, reached a steady state by week 5, and remained stable through the data cutoff of February 10, 2026, with all patients remaining LTP-free as of that date. 1 Banerji said durability questions will require continued follow-up but drew confidence from the longer-term phase 1 and phase 2 data.

Anticipated FDA Decision in H2 2027

A rolling BLA submission for lonvo-z was initiated in April, and the company continues to anticipate regulatory approval and a US launch in the first half of 2027.1 When asked which patients she would prioritize, Banerji said her view has shifted toward broad candidacy.

"I think that every patient is eligible," she said. "The concerns are going to be around insurance and navigating some of those challenges, but in terms of talking to patients… we are going to help them understand that this is a newer treatment that's coming up on the market...and then go through all of the data, the efficacy, the safety concerns, the potential benefit, [and] risks. [We] help them think through this in a shared decision-making process so that they themselves can be the person that decides [if] is this the right treatment for them.”

Editor’s note: Reported disclosures for Banerji include CSL Behring and BioCryst Pharmaceuticals.

References

1. Intellia Therapeutics. Intellia Therapeutics Reports Additional Positive Phase 3 Results for Lonvoguran Ziclumeran (lonvo-z) in Patients with Hereditary Angioedema. June 13, 2026. https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-reports-additional-positive-phase-3
2. Derman C. Single-Dose Lonvo-z Cuts HAE Attacks by 87% in Phase 3 Trial, With Aleena Banerji, MD. HCPLive. Published May 11, 2026. https://www.hcplive.com/view/single-dose-lonvo-z-cuts-hae-attacks-87-phase-3-trial-aleena-banerji-md