Intellia Therapeutics' Phase 3 trial for lonvo z demonstrated 87% reduction in hereditary angioedema attacks with 60% attack free patients, positioning it as the first potential in vivo CRISPR therapy. Despite these landmark clinical results and BLA submission initiation, the…
Intellia Therapeutics just proved something the biotech world has been waiting a decade to see: CRISPR gene editing works inside the human body.
A single infusion of its treatment lonvo-z cut hereditary angioedema attacks by 87% over six months, and kept 60% of patients entirely attack-free, according to Phase 3 results announced Monday. The stock fell 3%.
That disconnect is the story.
HAE is a rare genetic condition in which patients experience recurrent, potentially life-threatening swelling in the face, airway, abdomen, and extremities. Lonvo-z targets the KLKB1 gene, permanently disabling it to lower kallikrein and bradykinin levels. A single outpatient dose is designed to do this forever.
The 87% reduction and 60% attack-free rate are the numbers Intellia will put on its BLA submission, which the company initiated Monday. If the FDA agrees, lonvo-z reaches patients in the first half of 2027. It would be the first in-vivo CRISPR treatment approved anywhere and the second CRISPR drug ever, after Vertex and CRISPR Therapeutics' Casgevy won approval for sickle cell disease in December 2023.
But Wall Street sold the news. Investors had bid the stock up 35% in anticipation. When the actual data arrived, they took profits. The reasons matter.
The HAE market is not waiting for a CRISPR cure. It has several. Takeda's Takhzyro, approved in 2018, generates roughly $1.7 billion in annual sales and dominates the prophylaxis landscape. BioCryst's oral drug Orladeyo, approved in 2023, offers a pill instead of an injection. Ionis won approval for its RNA-targeting prophylactic Dawnzera in August 2025. The market for hereditary angioedema treatments is projected to reach $6 billion by 2030, but patients are sticky: most who have found a regimen that works see little reason to switch, even to a one-time cure.
"The patients that are on effective therapy, they're not motivated to change," Myles Minter, biotech analyst at William Blair, told BioSpace in December. "Any other treatments are just fighting to get a smaller piece of the pie."
Then there is the pricing question. Casgevy costs $2.2 million per patient. Intellia has not disclosed what lonvo-z will cost, but the benchmark is there, and the benchmark is staggering. The HAE community has spent years building infrastructure around chronic management; a one-time infusion priced like a car collection creates a reimbursement problem no payer has solved at scale.
There is also the overhang from Intellia's other major program. The company put its Nex-Z (NTLA-2001) gene editing therapy on clinical hold in January after a patient in the Phase 3 MAGNITUDE trial experienced a Grade 4 liver adverse event. The two programs use the same lipid nanoparticle delivery platform. Whether the FDA views that as a class-wide concern or a program-specific problem will shape how it reviews the lonvo-z BLA.
Lonvo-z itself showed a favorable safety profile in HAELO. No liver events of concern. But the market is not yet convinced that a company with one gene editing program on clinical hold and another awaiting approval should be valued as a platform rather than a single-asset biotech.
The data, meanwhile, is genuinely striking. Sixty percent attack-free at six months in a disease where patients have lived under constant threat of airway swelling is not a marginal result. The 87% reduction in mean monthly attack rate, from 2.10 to 0.26, compares favorably to every approved prophylactic. And because lonvo-z edits the KLKB1 gene permanently, it is designed to do this for the rest of the patient's life with a single dose.
Whether that durability claim holds over years rather than months, and whether the FDA's review of the first in-vivo CRISPR BLA surfaces any surprises, will determine whether the stock deserves to recover or whether the market is correctly pricing the gap between CRISPR's clinical promise and its commercial reality.
The science crossed a threshold Monday. The valuation has not yet decided what to do about it.