Intellia’s Phase 3 Clinical Trial for CRISPR-Based Gene Therapy Enrolls First Patient


The first patient in the trial, which is evaluating NTLA-2001 for the treatment of ATTR Amyloidosis, was enrolled at MedStar Washington Hospital Center.

Intellia Therapeutics and Regeneron have enrolled the first patient in their phase 3 MAGNITUDE clinical trial (NCT06128629) for NTLA-2001, an investigational CRISPR/Cas9-based gene therapy intended to treat transthyretin amyloidosis (ATTR) with cardiomyopathy (CM).1,2

The first patient enrolled in the multicenter study will be treated with the gene therapy at MedStar Washington Hospital Center in Washington DC. In the multinational, double-blind, trial, participants will be randomly assigned to receive treatment with either NTLA-2001 or a placebo intravenous (IV) infusion consisting of normal saline. The study is anticipated to enroll about 765 patients in total across sites in countries including the United States, Australia, the United Kingdom, New Zealand, and Canada. NTLA-2001, which is administered as a one-time IV infusion, is intended to deactivate the gene responsible for producing TTR in the liver, thus preventing or substantially reducing production of the misfolded protein that drives disease symptoms through build up in the body.

"It is with great excitement that our center has enrolled the first US patient in the MAGNITUDE trial, a pivotal study assessing a new avenue of treatment for human diseases, specifically ATTR-CM," Farooq Sheikh, MD, the medical director of the Advanced Heart Failure Program at MedStar Washington Hospital Center and the principal investigator of the MAGNITUDE study, said in a statement.1 "The MedStar Health Infiltrative Cardiomyopathy/Advanced Heart Failure Program is passionate about improving the lives of our patients in the region and beyond."

NTLA-2001 is also currently being evaluated in an ongoing phase 1 clinical trial (NCT04601051), data from which were presented at the 4th Annual ATTR Amyloidosis International Meeting, held November 2-3, 2023, in Madrid, Spain.3 It was reported that a single dose of NTLA-2001 yielded consistent, deep, and durable total serum TTR reductions in patients with ATTR-CM or ATTR with polyneuropathy with follow-up of up to 12 months. In terms of safety, NTLA-2001 was generally well-tolerated, with the most common adverse events being infusion-related reactions, which were mostly mild and resolved without sequelae.

“With 65 patients reported from the Phase 1 study, this update represents the largest clinical dataset for an in vivo CRISPR-based investigational therapy,” John Leonard, MD, the president and chief executive officer of Intellia, said in a November 2023 statement.4 “These positive interim results add to the growing body of data that demonstrates deep and durable reductions of serum TTR after a single dose of NTLA-2001.”

Last year, for World Amyloidosis Day, observed annually on October 26 by the patient and clinician communities, CGTLive® interviewed Ahmad Masri, MD, MS, a cardiologist at the Center for Hypertrophic Cardiomyopathy at Oregon Health & Science University, about the current landscape of care for ATTR amyloidosis and how NTLA-2001 could potentially transform this landscape. He went over some of the data generated by the gene therapy so far, noting that it has shown the ability to reduce production of TTR by more than 85% to 90% after a single dose.

“I encourage everyone to continue to learn about amyloidosis: systemic amyloidosis, ATTR amyloidosis, light chain amyloidosis, as well as other types of amyloidosis,” Masri said during the interview. “These are not ultra-rare diseases like people used to think. These are patients in our clinics not infrequently. I encourage everybody to continue to think about this, read about it, and use it as a case study for how things evolve over time... the whole landscape looks very different in 2023, compared to just 10 years ago.”

1. MedStar Health launches participation in phase 3 MAGNITUDE gene-editing study with first US Heart patient treated at MedStar Washington Hospital Center. News release. MedStar Health. May 2, 2024. Accessed May 6, 2024.
2. Intellia and Regeneron present updated interim data from phase 1 study of CRISPR-based NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis demonstrating that deep serum TTR reductions remained durable after a single dose. News release. Intellia Therapeutics, Inc. and Regeneron Pharmaceuticals, Inc. June 24, 2022. Accessed May 6, 2024.
3. Gillmore JD, Täubel J, Gane E, et al. Enabling the development of serum [TTR] as a biomarker for treatment of ATTR amyloidosis. Presented at: 4th Annual ATTR Amyloidosis International Meeting, November 2-3, 2023; Madrid, Spain.
4. Intellia presents new interim data from the ongoing phase 1 study of NTLA-2001 at the 4th International ATTR Amyloidosis Meeting. News release. Intellia Therapeutics. November 2, 2023. Accessed May 6, 2024.
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