almost a year later Intellia Therapeutics shows the world how its CRISPR-based therapy can safely edit genes in patients, the biotech now has additional clinical data showing that the treatment effect can be sustained. All doses tested resulted in lower levels of the pathogenic protein, a benefit that persisted for 12 months in the longest patients. Phase 1 clinical trials are continuing, but Intellia said it now plans to discuss a pivotal study with the FDA and other agencies that could support regulatory approval.
Intellia in Cambridge, Massachusetts shows the results Friday at the European Association for the Study of the Liver International Liver Congress, which will be held in London this year.
Intellia therapy NTLA-2001 is a potential treatment for hereditary transthyretin amyloidosis (hATTR). The disease is caused by a genetic defect that causes the liver to produce abnormal transthyretin. This protein accumulates in body tissues, including the heart and nerves. NTLA-2001 targets the liver, and a single dose of treatment is designed to spark editing efforts to inactivate genes at the root of hATTR to reduce levels of the problem protein. While currently available hATTR therapies must be taken long-term, Intellia’s gene-editing therapy is designed to be a one-time treatment.
A Phase 1 study is testing Intellia therapy in 15 patients with hATTR, which causes polyneuropathy. Part 1 of the study treated patients in four single escalating dose groups. At the lowest dose, treatment with NTLA-2001 resulted in a 52% reduction in blood transthyretin levels by day 28. Results rose significantly at the higher doses, decreasing by 87% and 86%, respectively, with an average of 93% for the 6 patients at the highest dose.
Patients in the two lowest-dose groups have been followed up for 12 months, and the results suggest that TTR reductions are persistent. In addition, 3 patients in the highest dose group had been followed up for 9 months and showed no evidence of TTR reduction. At all four doses, patients tolerated the treatment well, Intellia reported. Vomiting in one patient was reported as a potentially treatment-related serious adverse event, but the company noted that the patient also had a history of gastroparesis.
“Overall, we believe these data strongly support [NTLA] In 2001 it was possible to permanently reduce disease-causing proteins after a one-time treatment,” Chief Medical Officer David Lebwohl said on a Friday morning conference call.
With the encouraging results from Part 1 of the study, Intellia chose the 80 mg dose to test in Part 2. The extension study, which is evaluating the treatment in eight patients, is ongoing. The study is part of a 2016 collaboration between Intellia and Regeneron Pharmaceuticals. The hATTR portion of the consortium is evaluating NTLA-2001 as a treatment for patients with polyneuropathy or cardiomyopathy. Drug testing in cardiomyopathy patients is underway.
Enrollment in the polyneuropathy and cardiomyopathy group is expected to be completed later this year, Intellia CEO John Leonard said. Interim data from the cardiomyopathy segment are expected in the second half of 2022. Leonard added that as Intellia’s lead therapeutic candidate, additional clinical data on NTLA-2001 helps validate the company’s technology platform. Lessons from these studies will be applied to the rest of Intellia’s drug pipeline.
Polyneuropathy caused by hATTR can be treated with chronic therapy drugs from Alnylam Pharmaceuticals and Ionis Pharmaceuticals. Alnylam recently won FDA approval for its second hATTR therapy, Amvuttra. The drug, administered every three months, has an advantage over the company’s drug Patisiran, which is injected every three weeks. More hATTR competitions to come. Earlier this week, Ionis and partner AstraZeneca report positive Phase 3 data, which they say will support submission of an application seeking regulatory approval for its experimental treatment for hATTR polyneuropathy. This drug, eplontersen, is an injectable drug that is given once a month. Patients with cardiomyopathy caused by hATTR can be treated with the once-daily Vyndaqel pill sold by Pfizer.
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