CTX001 to Be Developed as Gene-Editing Therapy for Sickle Cell Disease

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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ARU-1801 research

Vertex Pharmaceuticals and CRISPR Therapeutics recently announced a joint collaboration to co-develop and co-commercialize CTX001 as a gene-editing treatment of diseases of hemoglobin, including β-thalassemia and sickle cell disease (SCD).

The announcement follows the presentation of preclinical data for CTX001 at the American Society of Hematology (ASH) Annual Meeting, Dec. 9-12, 2017, in San Diego, California.

“Over the past two years, we’ve made significant progress with CRISPR Therapeutics on the discovery and preclinical development of multiple CRISPR/Cas9-based treatments, and we’re pleased to select CTX001 as the first of these treatments to move into clinical development as part of our collaboration,” David Altshuler, MD, PhD, executive vice president of global research at Vertex, said in a press release.

“The addition of CTX001 to our clinical development pipeline provides us with a near-term opportunity to generate the first proof-of-concept clinical data for a CRISPR/Cas9-based medicine in two genetic diseases that are highly aligned with our research strategy.”

CTX001 will be the first gene-edited therapy as part of Vertex and CRISPR’s collaboration. CTX001 aims to make patients’ hematopoietic stem cells produce high levels of fetal hemoglobin in red blood cells. Fetal hemoglobin is a form of oxygen-carrying hemoglobin that is naturally present at birth and then normally replaced by its adult form.

In data presented at ASH 2017, CTX001 was shown to achieve greater than 90% editing of hematopoietic stem cells at the target site, leading to clinically relevant increases in fetal hemoglobin. CTX001 could potentially alleviate painful and debilitating sickle crises for SCD patients.

These data also support the application of CTX001 to move into Phase 1/2 clinical studies in β-thalassemia in Europe, in 2018, to evaluate its safety and effectiveness in adult transfusion-dependent β-thalassemia patients.

The two partners also are planning to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) in 2018 to support the initiation of a Phase 1/2 clinical trial in SCD in the U.S., also based on the preclinical data presented at ASH 2017.

“The submission of a Clinical Trial Application for CTX001 in Europe … reflects the advances we have achieved in translating the potential of CRISPR/Cas9 science into transformative therapies. We now look forward to working closely with Vertex as we initiate clinical trials next year,” said Samarth Kulkarni, PhD, chief executive officer of CRISPR Therapeutics. “The study of CTX001 in β-thalassemia will be the first company-sponsored clinical trial of a CRISPR-based therapy and is a major step forward for both the treatment of certain inherited blood diseases and for our collaboration with Vertex.”

CRISPR/Cas9 (short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9) is a new gene-editing technology that allows for precise, directed changes to genomic DNA.

According to the U.S. National Library of Medicine, the CRISPR/Cas9 system has generated a buzz in the scientific community because it is faster, cheaper, more accurate, and more efficient than other gene-editing methods.

CRISPR/Cas9 is being explored for a broad range of diseases, including single-gene disorders like SCD, hemophilia, and cystic fibrosis (CF). The technology also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, and human immunodeficiency virus (HIV) infections.