FDA Places Clinical Hold on IND Application for CTX001 for Sickle Cell Disease

The U.S. Food and Drug Administration placed a clinical hold on the investigational new drug (IND) application for CTX001, an experimental therapy for the treatment of sickle cell disease, according to a statement by CRISPR Therapeutics and Vertex Pharmaceuticals.

The hold on the clinical development of CTX001 will be in place until “certain questions that will be provided by the FDA as part of its review” of the IND process are resolved, the two companies said.

CTX001 uses gene editing technology to increase the production of fetal hemoglobin in patients’ red blood cells.

Fetal hemoglobin is a form of hemoglobin that naturally exists when babies are born and is later replaced with the adult form of hemoglobin.

For the treatment, doctors collect a patient’s own hematopoietic stem cells (cells from the bone marrow) and modify them in the laboratory so they can produce high levels of fetal hemoglobin.

These manipulated cells are then reintroduced into the patient’s body, where they will produce large amounts of red blood cells containing fetal hemoglobin, overcoming the hemoglobin deficiencies caused by sickle cell disease.

The IND was submitted to the FDA in April to support the planned initiation of a Phase ½ clinical trial in adults with sickle cell disease. The two companies expect to be able to answer the FDA’s questions in a timely fashion to continue clinical development of CTX001.

The planned European initiation of another Phase 1/2 study of CTX001 in adults with transfusion-dependent β-thalassemia remains on track, and the partners expect to initiate the trial this year.

The development of CTX001 as a gene-editing treatment of diseases of hemoglobin, including β-thalassemia and sickle cell disease, was announced in December 2017 by the two companies.

In data presented at the American Society of Hematology (ASH) Annual Meeting, also in December, CTX001 was shown to achieve greater than 90 percent editing of hematopoietic stem cells at the target site, leading to clinically relevant increases in fetal hemoglobin.

Based on these results, CTX001 could eventually help alleviate painful and debilitating sickle crises in patients.

These data supported the European application to initiate Phase 1/2 clinical testing of CTX001, as well as the IND application in the U.S.

CTX001 is being developed by CRISPR Therapeutics and Vertex as part of a research collaboration first established in 2015, aimed at discovering and developing gene editing treatments using the CRISPR/Cas9 technology.

CRISPR/Cas9 is a new gene-editing technology that has generated a buzz in scientific studies because it is reportedly faster, cheaper, more accurate, and more efficient than other gene-editing methods.