# Intellia files first in-vivo CRISPR therapy with the FDA
> Phase 3 HAELO cut hereditary-angioedema attacks 87%; rolling BLA for lonvo-z opens the path to the first marketed in-body gene edit

**Meta:** type: event · date: 2026-04-27 · heads: How Life Changes, The Long Game · 12 takes · 3 lenses · 4 regions

## Summary

[Intellia Therapeutics](/ko/entity/intellia) began a rolling FDA Biologics License Application on 27 April 2026 for lonvoguran ziclumeran ([lonvo-z](/ko/entity/in-vivo-editing), formerly NTLA-2002), a one-time [CRISPR](/ko/entity/crispr) edit of the [KLKB1](/ko/entity/gene-editing) gene to permanently lower kallikrein and bradykinin in [hereditary angioedema](/ko/entity/hereditary-angioedema). It is the first in-vivo CRISPR therapy to reach a US filing. In the 80-patient Phase 3 HAELO trial, lonvo-z cut attack rates 87% versus placebo (weeks 5–28); 62% of treated patients were completely attack-free and off prophylaxis, with no serious or grade ≥3 treatment-emergent events. The NEJM manuscript was published alongside June's EAACI Istanbul presentation. Intellia plans to complete the BLA in H2 2026 and launch in H1 2027 if approved.

## By the numbers

- 87%, reduction in HAE attack rate vs placebo (weeks 5–28).
- 62%, patients completely attack-free and off prophylactic therapy.
- 80, patients in the placebo-controlled Phase 3 HAELO trial.
- 1, number of doses (one-time treatment).
- H1 2027, planned US commercial launch if approved.

## Why it matters

A marketed in-body gene edit would shift CRISPR from one-off ex-vivo and bespoke cases to a repeatable, single-dose product, and set the regulatory template for permanent edits of common-ish disease genes. The KLKB1/liver target is the proof case; approval would validate the lipid-nanoparticle in-vivo delivery model Intellia and rivals are built on.

## What to watch

- BLA completion (H2 2026) and any FDA advisory-committee scheduling.
- Long-term durability/safety data beyond the ~7.5-month median follow-up.
- Whether the precedent accelerates in-vivo filings from Beam, Verve and others.

## Regional takes (batched by bias / lens)

### unlabelled
- **Intellia Therapeutics (BLA release)** (United States, en) — Intellia's own announcement, 27 Apr 2026, that it has begun a rolling BLA submission to the FDA for lonvoguran ziclumeran (lonvo-z, formerly NTLA-2002), a one-time in-vivo CRISPR edit of the KLKB1 gene; submission to complete H2 2026, US launch planned H1 2027 if approved.
  Source: https://ir.intelliatx.com/news-releases/news-release-details/intellia-therapeutics-initiates-rolling-submission-biologics
- **Intellia Therapeutics (Phase 3 results)** (United States, en) — Full Phase 3 HAELO readout: 80 patients, 87% reduction in HAE attack rate vs placebo (weeks 5–28), 62% completely attack-free and off prophylaxis; no serious or grade ≥3 treatment-emergent events in the lonvo-z arm.
  Source: https://www.globenewswire.com/news-release/2026/04/27/3281473/0/en/intellia-therapeutics-reports-positive-phase-3-results-in-hereditary-angioedema-marking-a-global-first-for-in-vivo-gene-editing.html
- **CRISPR Medicine News** (Denmark, en) — 
  Source: https://crisprmedicinenews.com/news/intellia-files-bla-after-lonvo-z-meets-phase-3-endpoints/
- **BioSpace** (United States, en) — 
  Source: https://www.biospace.com/press-releases/intellia-therapeutics-initiates-rolling-submission-of-biologics-license-application-to-fda-for-lonvoguran-ziclumeran-lonvo-z-as-a-one-time-treatment-for-hereditary-angioedema
- **Big Molecule Watch** (United States, en) — 
  Source: https://www.bigmoleculewatch.com/2026/04/28/intellia-initiates-rolling-bla-submission-for-in-vivo-crispr-therapy-in-hereditary-angioedema/
- **StockTitan** (United States, en) — 
  Source: https://www.stocktitan.net/news/NTLA/intellia-therapeutics-reports-additional-positive-phase-3-results-afks73wvycew.html
- **BioSpace (EAACI 2026 data)** (United States, en) — 
  Source: https://www.biospace.com/press-releases/intellia-therapeutics-to-report-additional-phase-3-haelo-data-for-lonvoguran-ziclumeran-lonvo-z-in-late-breaking-oral-presentation-at-eaaci-2026
- **SEC (Form 8-K)** (United States, en) — 
  Source: https://www.sec.gov/Archives/edgar/data/0001652130/000119312526270358/ntla-ex99_1.htm
- **Innovative Genomics Institute** (United States, en) — 
  Source: https://innovativegenomics.org/news/crispr-clinical-trials-2026/
- **FBAE (CRISPR trials 2026)** (India, en) — 
  Source: https://www.fbae.org/blog/crispr-clinical-trials-2026/

### clinical / sector
- **The Medicine Maker** (United Kingdom, en) — Reports the double-blind HAELO trial as the confirmation regulators need to approve the first in-vivo CRISPR treatment, with the NEJM manuscript published simultaneously to the June EAACI Istanbul presentation; positions it as a category-defining single-dose edit.
  > "A one-time in-vivo CRISPR therapy has significantly reduced attacks in patients with hereditary angioedema in a phase 3 trial."
  Source: https://themedicinemaker.com/issues/2026/articles/june/in-vivo-crispr-therapy-succeeds-in-phase-3-trial/

### scientific
- **Nature Biotechnology** (United Kingdom, en) — Frames Intellia's filing as the field's first in-vivo CRISPR therapy reaching the FDA, contrasting permanent in-body editing of a liver gene against ex-vivo approaches and flagging the regulatory precedent a one-time genome edit sets.
  > "Intellia heads to FDA with first in vivo CRISPR-based gene editing therapy."
  Source: https://www.nature.com/articles/s41587-026-03154-9

## Across the graph
- Related: [[china-invivo-gene-editing-2026]], [[newlimit-series-c-reprogramming-2026]]
- Entities: Intellia, Crispr, Gene Editing, In Vivo Editing, Fda, Hereditary Angioedema

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Canonical: https://rbtfl.xyz/ko/n/intellia-lonvo-z-invivo-crispr-bla-2026