FDA lifts hold on Vertex and CRISPR Therapeutics sickle cell therapy

The FDA has lifted the clinical hold on the trial of a CRISPR gene-editing therapy CTX001 in patients with of sickle cell disease (SCD), enabling partners Vertex and CRISPR Therapeutics to begin the study by the end of 2018.

The US regulator placed a hold on the trial in May, which could now become the first in human trials of the CRISPR technology.

At the time, the companies said the FDA had posed additional questions in its review of its IND trial submission, but haven’t offered any further details when announcing the lifting of the hold this week.

CTX001 is an investigational, autologous, gene-edited haematopoietic stem cell therapy for patients suffering from severe haemoglobinopathies. 

The partners are developing it for both β-thalassemia and sickle cell disease (SCD). It already has a rival gene therapy ahead of it: Bluebird’s LentiGlobin has just been submitted to the European Medicines Agency for review, potentially setting it up for approval in 2019.

Vertex and CRISPR Therapeutics also announced that they have gained permission to begin trials of CTX001 in a number of others countries for both β-thalassemia and SCD. They say they are on track to initiate a phase 1/2 clinical study in SCD by the end of 2018 and are currently enrolling patients with transfusion dependent β-thalassemia in a phase 1/2 trial in β-thalassemia in Europe.

Samarth Kulkani

For CRISPR Therapeutics, led by chief executive Dr Samarth Kulkani, and co-founded by Emmanuelle Charpentier, one of the co-developers of the CRISPR technology, the last few months have been sobering.

The company’s share price had risen rapidly over the last few years, and its market capitalisation reached $2.5bn, despite there being no evidence that the technology could work safely and effectively in humans. Since the hold has been in place, it share price has fallen back around 50%, although its market cap is still at $1.9bn.

CTX001 is an investigational ex vivo CRISPR gene-edited therapy for patients suffering from β-thalassemia or sickle cell disease in which a patient's hematopoietic stem cells are engineered to produce high levels of foetal haemoglobin (HbF; haemoglobin F) in red blood cells.

The partners are also working on a CRISPR therapy for cystic fibrosis (CF), the therapeutic focus of Vertex.