Intellia Therapeutics, building exterior and company sign, Cambridge, Massachusetts, United States.
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Intellia Therapeutics said its Crispr-based treatment for a rare bloating condition met its goals in a late-stage trial, marking a milestone for the field of gene editing and putting the company on track to seek approval from the U.S. Food and Drug Administration.
The company's treatment uses Nobel Prize-winning Crispr technology to edit DNA and disable the gene that controls the production of a peptide that is overactive in people with hereditary angioedema, causing life-threatening swelling attacks. The Intellia treatment is administered once via an hour-long infusion, making the edits directly into the liver.
Intellia said the single treatment reduced attacks by 87% compared to a placebo, meeting the study's primary objective. Six months after treatment, 62 percent of patients were seizure-free and were not using other therapies, Intellia said.
The company described the safety and tolerability of the treatment as “favorable,” reporting that the most common side effects were infusion-related reactions, headaches and fatigue. Analysts were closely watching the safety of the trial, as one patient died in a separate trial of a treatment other than Intellia. That patient developed liver injury and ultimately died of septic shock after an ulcer, according to the company.
“When you think about where we started with Crispr, just 12 years ago with some of the fundamental knowledge, I think there was a lot of talk about what might be possible, and we've had reports along the way in terms of milestones, but this is the first Phase 3 data in any indication with Crispr in vivo where you're actually changing a disease-causing gene,” said Intellia CEO John Leonard.
The only Crispr-based drug approved by the FDA comes from Vertex Pharmaceuticals. Called Casgevy, gene editing is performed outside the body or ex vivo. The process requires collecting a person's blood cells, making the modifications outside the body, and then reinfusing them back into the patient. Meanwhile, the Intellia treatment makes the edits inside the body or in vivo.
Intellia said it has initiated a continuing application with the FDA and plans to complete the filing in the second half of this year. The company hopes to launch the treatment in the US in the first half of next year, if approved.
If approved, Intellia's treatment, lonvoguran ziclumeran, will compete with about a dozen other chronic HAE medications. Despite the appeal of a single treatment, genetic drugs have not always been commercially successful. BioMarin withdrew its gene therapy for hemophilia A due, for example, to weak sales.
Leonard said there are important differences between the two, such as the fact that BioMarin's therapy faced questions about how long the effects would last. In contrast, he said Intellia has not seen a single case in nearly six years where the effects have diminished over time.
Despite the results, he is reluctant to call the Intellia treatment a functional cure.
“I think this is a turning point for the disease and a turning point for Crispr-based in vivo therapy where a change can be made. [and] “It's permanent,” Leonard said. “And, as far as we know, we don't have a single patient in this program or any other program where there has been any diminishment of the effect of what we did to the gene or the effect of what we've seen with the clinical aspects of the disease itself. So it's pretty exciting.”
Clarification: This story was updated to clarify that a patient in a separate trial of a different Intellia treatment developed acute liver injury and ultimately died of septic shock following an ulcer.
