Intellia Therapeutics, based in Cambridge, Massachusetts, reported promising results from the Phase II clinical trial of NTLA-2002, a CRISPR-based therapy targeting hereditary angioedema (HAE), a rare and potentially life-threatening genetic condition. People with HAE experience attacks of severe swelling, which can affect the hands, feet, genitals, stomach, face and throat. The clinical trial, which compared the results of a single 25 mg or 50 mg dose, met all primary and secondary endpoints, demonstrating the treatment’s potential to offer long-lasting control of HAE attacks with just one dose.
Safety and Efficacy Confirmed
In addition to demonstrating NTLA-2002’s efficacy, the trial also reaffirmed its safety. The company reported that no new safety concerns emerged during the trial; most adverse events reported were mild. This aligns with the safety profile observed in earlier trials.
At the 2024 European Academy of Allergy and Clinical Immunology Congress, Intellia presented long-term data from an ongoing Phase I trial in which 8 out of 10 patients remained completely attack-free for over 18 months following a single dose. Some patients have gone more than two years without experiencing an attack, underscoring the potential for NTLA-2002 to provide long-lasting relief. The therapy led to a 98% reduction in monthly attack rates among all patients.
Evaluating Effects of Single-Dose Treatment
NTLA-2002 is designed to disable the KLKB1 gene in the liver, a driver of the overproduction of kallikrein, a protein that contributes to swelling in patients with HAE. In the Phase II trial, both the 25 mg and 50 mg doses led to “deep reductions in attacks” in the 16-week observation period. However, the 50 mg dose showed even greater effectiveness in eliminating attacks for a larger percentage of patients. Based on these findings, Intellia will advance the 50 mg dose into a pivotal Phase III trial, further evaluating the therapy’s potential as a one-time treatment for patients with HAE.
Intellia President and Chief Executive Officer John Leonard expressed the company’s excitement in a statement. “Based on these positive results and our recent successful end-of-Phase II meeting with the FDA, we see a clear path to initiating the Phase III trial in the coming months.” He said the company will present detailed results of the Phase II trial at a medical conference. According to Leonard, NTLA-2002 could offer lifelong control of the condition, bringing renewed hope to patients and families affected by HAE.
The upcoming Phase III trial is expected to be a global effort, and the company anticipates recruiting a broad range of patients. The data from this trial will be critical in confirming NTLA-2002’s safety and efficacy in a larger population.
Looking Ahead, Beyond HAE
Intellia faces competition from treatments like Takeda’s monoclonal antibody Takhzyro® and Ionis Pharmaceuticals’ RNA drug donidalorsen, which has shown positive Phase III results. In an earnings call, Leonard emphasized the company’s focus on meeting patient needs: “They’re not looking for minor improvements in prophylactic therapy, they’re not looking for primarily extensions in dosing intervals. What they’re looking for is to be as normal as possible, and that means not having to take any medicines.”
Beyond HAE, Intellia is advancing other CRISPR-based therapies to treat various genetic diseases. The company is enrolling patients in a Phase III trial of NTLA-2001 to treat transthyretin (ATTR) amyloidosis with cardiomyopathy. In addition, it is planning to begin a Phase I/II trial of NTLA-3001, a CRISPR-mediated gene insertion candidate to treat alpha-1 antitrypsin deficiency. These therapies, like NTLA-2002, are designed to offer long-term or permanent solutions after a single dose. As Leonard commented in a statement, “With three pivotal Phase III trials and our first gene insertion trial expected to be active by year-end, Intellia is closer than ever to transforming the future of medicine with our one-time, in vivo gene editing therapies.”
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