CRISPR Clinical Trials – Latest News Updates

NTLA-2001 study expansion to include adults with transthyretin amyloidosis with cardiomyopathy

Last week, Intellia Therapeutics announced that the UK’s Medicines and Healthcare products Regulatory Agency had approved a protocol amendment to the ongoing Phase 1 NTLA-2001 trial to include patients with ATTR amyloidosis with cardiomyopathy (ATTR-CM).

This amendment means that Intellia and its collaborator Regeneron Pharmaceuticals can now begin to enroll up to 36 adults in the UK with either hereditary ATTR-CM (ATTRv-CM) or wild-type cardiomyopathy (ATTRwt-CM), and New York Heart Association Class I – III heart failure. These new patients will be enrolled in new dose-escalation and expansion cohorts, and will serve as an addition to the original Phase 1 study population, which includes patients with ATTR amyloidosis with polyneuropathy (ATTRv-PN).

NTLA-2001 is the first-ever in vivo CRISPR-Cas9 therapy

In ATTR amyloidosis, a protein known as transthyretin (TRR) is misfolded, which accumulates as amyloid fibrils in tissues throughout the body and causes often-fatal complications that primarily involve the heart and nerves.

NTLA-2001 comprises a TTR-targeting gRNA and Cas9 mRNA, both of which are delivered systemically to target the liver using Intellia’s proprietary lipid nanoparticle (LNP) delivery technology. The therapeutic strategy behind NTLA-2001 is that it will selectively reduce the concentration of transthyretin (TTR) protein in serum through CRISPR-based inactivation of the TTR gene in liver cells.

NTLA-2001 was the first ever CRISPR-Cas9-based precision genome-editing therapy to be administered systemically to humans via intravenous infusion (IV). In June 2021, Intellia and Regeneron shared positive interim clinical results from the first two cohorts of the trial, which were later published in New England Journal of Medicine, marking the first-ever clinical data supporting in vivo CRISPR genome editing in humans. You can read more about the interim clinical data our previous NTLA-2001 clinical trial update.

NTLA-2001 has already received orphan drug designation for the treatment of ATTR amyloidosis by both the European Commission and the U.S. FDA.

Regenerative Medicine Advanced Therapy designation for CTX110™ for B-cell cancers

CRISPR Therapeutics announced last week in a press release that the U.S. FDA had granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX110™, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies.

The RMAT designation is a dedicated programme designed to expedite the drug development and review processes for promising pipeline products, including genetic therapies, and according to the company's press release, RMAT designation for CTX110™ is based on encouraging clinical data presented so far.

CTX110 is a donor-derived CAR-T cell therapy that targets CD19⁺ cancers

CTX110 is an allogeneic (donor-derived) CAR-T therapy designed to target CD19, a B cell-specific cell surface antigen expressed in all B cell lineage malignancies. CTX110 is developed ex vivo using CRISR-Cas9 technology in a one-step multiplex gene-editing workflow. These edits target a CAR to CD19, disrupt major histocompatibility complex (MHC) I to improve persistance, and ensure insertion of the recombinant CAR into the T cell receptor (TCR) alpha constant (TRAC) locus. Inserting the CAR into this locus places the CAR under endogenous TCR regulation, while simultaneously disrupting the native TCR, thus mitigating the risk of graft-vs-host disease (GVHD) that may otherwise result from histo-incompatibility between a donor and recipient.

CTX110 is being investigated in two clinical trials for cancer. The first is CARBON, a Phase 1 open-label, multicenter study to evaluate the safety and efficacy of several doses of CTX110 in adult patients with relapsed or refractory non-Hodgkin lymphoma, who have received at least two prior lines of therapy. The second trial, is a single-arm, open-label, multicenter study to assess safety and efficacy of CTX110 in patients with relapsed or refractory B cell cancer.

In October 2021, CRISPR Therapeutics reported positive efficacy and safety results from the ongoing Phase 1 CARBON trial of CTX110™ in relapsed or refractory CD19+ B-cell malignancies.

CTX110 is one of three clinical-stage allogeneic CRISPR-Cas9 CAR-T cell candidates under development by CRISPR Therapeutics for the treatment of cancer. You can read more about the company’s clinical-stage candidates in a previous article.

We strive to keep you updated with clinical and pre-clinical news from the CRISPR Medicine field. For a complete overview of current gene editing clinical trials, check out CRISPR Medicine News' Clinical Trials Database.