BioPharma, Pharma

New data for Intellia’s CRISPR therapy shows potential for one-time treatment of a rare disease

An Intellia Therapeutics therapy that uses CRISPR to perform in vivo genomic edits has clinical data showing that the therapeutic effects continue for a year in patients. The biotech now plans to speak with regulators about the design for a pivotal clinical trial testing this therapy, a potential one-time treatment for a rare inherited disease.


Nearly a year after Intellia Therapeutics showed the world how its CRISPR-based therapy safely edits genes inside a patient, the biotech now has additional clinical data indicating that the therapeutic effects can last. All doses tested led to reductions in levels of a disease-causing protein, a benefit that is sustained 12 months in the patients followed the longest. The Phase 1 clinical trial is continuing, but Intellia says it now plans to speak with the FDA and other agencies about a pivotal study that could support regulatory approval.

Cambridge, Massachusetts-based Intellia presented the results on Friday at the European Association for the Study of the Liver International Liver Congress, which is taking place this year in London.

The Intellia therapy, NTLA-2001, is a potential treatment for hereditary transythyretin amyloidosis (hATTR). This disease is caused by a genetic defect that causes the liver to produce abnormal versions of the protein transthyretin. This protein builds up in bodily tissue, including the heart and nerves. NTLA-2001 targets the liver, where a single dose of the therapy is designed to spark editing work that inactivates the gene at the root of hATTR in order to reduce levels of the problem protein. Whereas currently available therapies for hATTR must be taken chronically, Intellia’s gene-editing therapy is intended to be a one-time treatment.

The Phase 1 study is testing the Intellia therapy in 15 hATTR patients whose disease is causing polyneuropathy. Part 1 of the study treated patients across four single-ascending dose groups. In the lowest dose, treatment with NTLA-2001 led to a 52% reduction of transthyretin levels in the blood by day 28. The results ramped up considerably at higher doses, reaching reductions of 87%, 86%, and at the highest dose, an average of 93% in six patients.

Patients in the two lowest dose groups have reached 12 months of follow-up with results showing that the TTR reductions are sustained. Also, three patients in the highest dose group have reached nine months of follow-up with no signs of a loss in TTR reduction. At all four doses, Intellia reported that the patients tolerated the therapy well. Vomiting in one patient was reported as a serious adverse event possibly related to the treatment, but the company noted that this patient also has a history of gastroparesis.

“In totality, we believe these data strongly support [NTLA] 2001’s potential to provide a permanent reduction in the disease-causing protein after a one-time treatment,” Chief Medical Officer David Lebwohl said during a Friday morning conference call.

With the encouraging results from Part 1 of the study, Intellia selected an 80 mg dose for testing in Part 2. This expansion study, which is evaluating the therapy in eight patients, is ongoing. The study is part of a collaboration that Intellia struck up with Regeneron Pharmaceuticals in 2016. The hATTR part of the alliance is evaluating NTLA-2001 as a treatment for patients who have either polyneuropathy or cardiomyopathy. The test of the drug in patients with cardiomyopathy is ongoing.

Intellia CEO John Leonard said that enrollment in both the polyneuropathy and cardiomyopathy arms is expected to be completed later this year. Interim data from the cardiomyopathy arm are expected in the second half of 2022. Leonard added that as Intellia’s lead therapeutic candidate, the additional clinical data for NTLA-2001 help to validate the company’s technology platform. The learnings from these studies will be applied to the rest of the Intellia drug pipeline.

Polyneuropathy caused by hATTR can be treated by drugs from Alnylam Pharmaceuticals and Ionis Pharmaceuticals that are chronic therapies. Alnylam recently won FDA approval for its second hATTR therapy, Amvuttra. That drug’s every three months dosing offers an edge over the company’s drug Patisiran, which is infused every three weeks. More hATTR competition is coming. Earlier this week, Ionis and partner AstraZeneca reported positive Phase 3 data that they said will support submissions seeking regulatory approval for their experimental treatment for hATTR polyneuropathy. That drug, eplontersen, is an injection drug given once a month. Patients whose hATTR causes cardiomyopathy can be treated with Vyndaqel, a once-daily pill marketed by Pfizer.

Public domain image by Flickr user NIH Image Gallery