Intellia and Regeneron Announce Landmark Clinical Data Showing Deep Reduction in Disease-Causing Protein After Single Infusion of NTLA-2001, an Investigational CRISPR Therapy for Transthyretin (ATTR) Amyloidosis
- First-ever clinical data supporting safety and efficacy of in vivo CRISPR genome editing in humans
- Interim readout in ongoing Phase 1 trial finds single 0.3 mg/kg dose of NTLA-2001 led to 87% mean reduction in serum TTR, with a maximum 96% serum TTR reduction by day 28, with dose-dependent response
- Encouraging safety profile; no serious adverse events observed in the first six patients by day 28
- Data published in
The New England Journal of Medicineand presented at Peripheral Nerve SocietyAnnual Meeting (PNS)
- Intellia to host investor event on
Monday, June 28at 8:00 a.m. E.T.
“These are the first ever clinical data suggesting that we can precisely edit target cells within the body to treat genetic disease with a single intravenous infusion of CRISPR. The interim results support our belief that NTLA-2001 has the potential to halt and reverse the devastating complications of ATTR amyloidosis with a single dose,” said Intellia President and Chief Executive Officer
The interim data released today cover the first six ATTRv-PN patients across two single-ascending dose cohorts of the Phase 1 study, which is currently being conducted in the
“This is exciting early data both for people living with this devastating disease and for the entire scientific community working to maximize the potential of genetics-based medicines through cutting-edge research and technologies,” said
At both dose levels, NTLA-2001 was generally well-tolerated by the six patients included in the interim analysis, with no serious adverse events and no liver findings by day 28. Given the safety and tolerability profile so far, NTLA-2001 is continuing to be evaluated in the dose-escalation portion of the study, to determine if a higher dose could result in a deeper reduction in disease-causing protein levels leading to the potential for more meaningful clinical benefit. As of the date of this release, Cohort 3, evaluating NTLA-2001 at the 1 mg/kg dose level, is actively enrolling.
Following the identification of a recommended dose in the dose-escalation portion of the study, Intellia expects to begin a single-dose expansion cohort in Part 2 of the Phase 1 trial later this year. After completion of the Phase 1 trial, the company plans to move to pivotal studies for both polyneuropathy and cardiomyopathy manifestations of ATTR amyloidosis.
“ATTR amyloidosis is a progressive and fatal disease that usually requires chronic, lifelong treatment. These interim Phase 1 data support NTLA-2001 as the only one-time treatment either on the market or in development,” said
Intellia intends to present additional data from the study at a medical or scientific meeting later this year.
1 Gillmore JD, Gane E, Taubel J, et al. CRISPR /Cas9 In
Intellia Therapeutics Investor Event and Webcast Information
Intellia will host a live webcast on
Based on Nobel Prize-winning CRISPR/Cas9 technology, NTLA-2001 could potentially be the first curative treatment for ATTR amyloidosis. NTLA-2001 is the first investigational CRISPR therapy candidate to be administered systemically, or through a vein, to edit genes inside the human body. Intellia’s proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-part genome editing system: guide RNA specific to the disease-causing gene and messenger RNA that encodes the Cas9 enzyme, which carries out the precision editing. Robust preclinical data, showing deep and long-lasting transthyretin (TTR) reduction following in vivo inactivation of the target gene, supports NTLA-2001’s potential as a single-administration therapeutic. Interim Phase 1 clinical data released in
About the NTLA-2001 Clinical Program
The global Phase 1 trial is an open-label, multi-center, two-part study of NTLA-2001 in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). The trial’s primary objectives are to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of NTLA-2001. Patients receive a single dose of NTLA-2001 via intravenous administration. The study will enroll up to 38 participants (ages 18-80 years) and consists of a single-ascending dose phase followed by a dose-expansion phase, which is expected to begin later in 2021. Visit clinicaltrials.gov (NCT04601051) or eudract.ema.europa.eu/ (2020-002034-32) for more details.
Enrollment is ongoing at clinical trial sites in the
About Transthyretin (ATTR) Amyloidosis
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
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Source: Intellia Therapeutics, Inc.