Intellia’s CRISPR-Engineered Cell Therapy Receives Orphan Drug Designation for Acute Myeloid Leukemia


The first patient was dosed in the phase 1/2a trial earlier in March 2022.

The FDA has granted orphan drug designation to Intellia Therapeutics’ novel T-cell receptor (TCR) T-cell therapy NTLA-5001 for the potential treatment of acute myeloid leukemia (AML).

“The FDA’s decision to grant orphan drug designation for NTLA-5001 reflects the serious need for novel treatment options for people living with AML, a disease with notably poor long-term survival,” John Leonard, MD, president and chief executive officer, Intellia, said in a statement.1 “As part of our full-spectrum genome editing strategy, we seek to leverage our proprietary CRISPR/Cas9-based platform to engineer differentiated cell therapies targeting cancers for which there are currently limited or no treatment options. We look forward to advancing our investigational TCR-T cell therapy, NTLA-5001, through the clinic in hopes of improving future treatment options for patients in need.” 

The TCR-T cell therapy, Intellia’s first ex vivo CRISPR therapy that targets the Wilms’ Tumor 1 antigen, is currently being evaluated in a phase 1/2a study (NCT05066165) in adults with persistent or recurrent AML. Intellia announced earlier in March that the first patient had been dosed in the study.

The study will evaluate the therapy’s safety, tolerability, cell kinetics, and anti-tumor activity with dose escalation and expansion phases in 2 arms stratified according to disease burden, with a planned enrollment of up to 54 participants. The primary endpoint is safety as measured by adverse events (AEs) and any dose-limiting toxicities. Secondary endpoints include cell kinetics of NTLA-5001 via frequency of NTLA 5001 TCR transgene copy, tumor response, response duration, and disease progression.

READ MORE: Around the Helix: Cell and Gene Therapy Company Updates – March 9, 2022

"This NTLA-5001 milestone represents a significant step forward in our full-spectrum approach to genome editing,” Leonard said in a previous statement.2 “AML is the most common type of acute leukemia in adults, where despite recent advancements, a significant therapeutic need still exists. We look forward to advancing this investigational engineered cell therapy as a treatment for people living with this aggressive cancer of the blood and bone marrow.”

The company also recently announced updated data on NTLA-2001, Intellia and Regeneron’s investigational CRISPR-Cas9 therapy.3 Data from a phase 1 study (NCT04601051) showed deep and sustained reductions of transthyretin (TTR) protein in patients with hereditary transthyretin (ATTR) amyloidosis with polyneuropathy (ATTRv-PN).3 These data further support the systemic administration of a CRISPR-Cas9 gene-editing therapy.

Investigators observed dose-dependent reductions in serum TTR, with peak reductions by day 28. Mean reductions were 52%, 87%, and 86% in 3 patients each in the first 3 cohorts and 93% in the 6 patients in the highest cohort. Mean serum TTR reductions were durable throughout patient follow-up, which ranged from 2 to 12 months. Reductions were also consistent across all dose levels greater than 0.1 mg/kg. All patients at the highest dose level had over an 80% serum TTR reduction and most (n = 4) had an over 90% reduction by day 28. All patients in this cohort had sustained reductions in TTR.

Despite progress with their CRISPR-based therapies, Intellia was recently dealt a blow after the US Patent and Trademark Office passed down a decision4 in favor of the Broad Institute of Harvard University and the Massachusetts Institute of Technology, noting that they were the first to invent CRISPR/Cas9 editing in eukaryotic cells – not the group known collectively as CVC, which includes the University of California (UC), University of Vienna, and Emmanuelle Charpentier, PhD, of whom Intellia is associated with and licenses technology from. The CVC group has said that they plan to challenge the decision.5

1. Intellia Therapeutics receives U.S. FDA orphan drug designation for NTLA-5001 for the treatment of acute myeloid leukemia. News release. Intellia Therapeutics. March 9, 2022.
2. Intellia Therapeutics announces first patient dosed in phase 1/2a clinical trial of NTLA-5001 for the treatment of acute myeloid leukemia. News release. Intellia Therapeutics. March 1, 2022.
3. Intellia and Regeneron announce updated phase 1 data demonstrating a single dose of NTLA-2001, an investigational CRISPR therapy for transthyretin (ATTR) amyloidosis, resulted in rapid, deep and sustained reduction in disease-causing protein. News release. Intellia Therapeutics. February 28, 2022.
4. Patent Interference No. 106,115 (DK): Decision on Priority 37 C.F.R. § 41.125(a). USPTO. February 28, 2022. Accessed March 3, 2022.\
5. U.S. patent appeal board rules against UC in CRISPR interference. News release. UC Berkeley. February 28, 2022.
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