An experimental Intellia Therapeutics medicine that uses CRISPR technology to edit genes inside patients led to a significant reduction in attacks from a rare inherited swelling disorder after just a single dose. Based on the preliminary Phase 3 data, Intellia said Monday it has filed a submission seeking FDA approval of what could become the first in vivo gene-editing therapy to reach the market for any disease.
An approval of the Intellia therapy would introduce an important new treatment option for patients with hereditary angioedema, or HAE. While this disorder is seeing innovation coming from a growing number of drugs, they’re all chronic medications competing to offer advantages in dosing frequency and convenience. Intellia’s genetic medicine could become the first one-time treatment for HAE.
HAE leads to bouts of swelling that come without warning in various parts of the body. A swelling attack can become fatal if it closes off a patient’s airway. The swelling develops from overproduction of bradykinin, a peptide that plays a role in inflammatory responses. Many of the available HAE medications either block bradykinin or proteins related to that target. Unlike those chronic medications, Cambridge, Massachusetts-based Intellia is aiming for a permanent fix. Its therapy, lonvoguran ziclumeran or lonvo-z, uses CRISPR to inactivate a gene in the liver that provides the instructions for making proteins that activate bradykinin.
Lonvo-z is being evaluated in a placebo-controlled Phase 3 study that enrolled 80 adults and adolescents age 16 and older; 52 received Intellia’s therapy and 28 received a placebo. Some of the available HAE drugs prevent swelling attacks. Patients who were taking such therapies were required to stop in the weeks prior to dosing in the clinical trial.
In the results reported Monday, Intellia said a one-time infusion of lonvo-z reduced swelling attacks by 87% compared to a placebo in the evaluation period from weeks 5 to 28. Results also showed 62% of patients treated with the study drug were attack free and therapy free in this period compared to 11% in the control arm. The study is continuing to follow patients through week 104. Intellia said the most common adverse events reported to date were infusion-related reactions, headache, and fatigue. The company described these events as mild or moderate.
Intellia said more detailed data from the trial so far will be presented in June during the 2026 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Istanbul. One part of the study where clinicians and investors may want more information is a case of high liver enzymes, which can be a sign of drug toxicity. In an investor presentation, Intellia said this case self-resolved in one week.
Liver safety is something people have been watching in Intellia’s CRISPR medicines after one patient in a different Phase 3 study was hospitalized for liver complications last fall. The safety signal led the FDA to place a clinical hold on two pivotal Intellia tests of this CRISPR-editing therapy, nex-z, in transthyretin amyloidosis. In March, the FDA lifted the hold with the company and the regulator in agreement on enhanced monitoring for liver problems and short-term steroid treatment if these complications emerge after dosing.
In a research note, William Blair analysts Myles Minter and John Boyle pointed out that Intellia’s in vivo gene-editing platform has elicited multiple Grade 4 liver enzyme spikes associated with nex-z. While there are similarities in delivery and genetic payload between the two Intellia therapies, the analysts said it is difficult to assess if the safety concerns around nex-z read through to lonvo-z. That said, they see the safety profile to date for the HAE therapy as supportive of regulatory approval.
“Although we await further data at EAACI, the lonvo-z efficacy profile looks compelling in our view relative to competition and how well the one-and-done message will resonate with patients and clinicians over other chronic prophylactic options will be key,” the analysts said. “Pricing is a focus here with lonvo-z being the first potentially approved in vivo gene-editing therapy and management messaging a likely premium to at least the yearly [wholesale acquisition cost] prices of currently approved chronic prophylactic injectable options.”
One of those prophylactic injectable options is a genetic medicine. Last summer, the FDA approved Dawnzera, an antisense oligonucleotide developed by Ionis Pharmaceuticals. This drug binds to messenger RNA carrying instructions for making a protein involved in the pathway that leads to HAE inflammation. But Dawnzera is a chronic medication administered via an autoinjector every four or eight weeks. Ionis set a $57,462 per dose wholesale price for this drug, which amounts to $747,000 annually for every four weeks dosing.
Intellia’s application seeking FDA approval for lonvo-z is a rolling submission. The company said it expects to complete this submission in the second half of this year. If approved, Intellia expects to launch lonvo-z in the first half of 2027.
Photo: Yuichiro Chino, Getty Images
