Vertex and partner CRISPR Therapeutics have revealed initial positive data from the first two patients treated with investigational CRISPR/Cas9 gene-editing therapy CTX001.
The impressive data suggests that the two patients could potentially have been cured of their diseases. The two patients have severe haemoglobinopathies – including transfusion-dependant beta thalassaemia (TDT) and severe sickle cell disease (SCD).
The TDT patient received CTX001 in the first quarter of 2019 and the data for this patient reflects nine months of safety and efficacy follow-up. Prior to enrolling in the study, the TDT patient required 16.5 transfusions per year.
At nine months of CTX001 infusion, the patient was transfusion independent and had total haemoglobin levels of 11.9 g/dL, 10.1 g/dL fetal haemoglobin and 99.8% F-cells.
The SCD patient experienced seven vaso-occlusive crises (VOC) per year before enrolling in the study. At four months after CTX001 infusion, the patient was free of VOCs and had total haemoglobin levels of 11.3 g/dL, 46.6% fetal haemoglobin and 94.7% F-cells.
However, both patients experienced side effects during treatment with CTX001, but the principal investigator did not consider these adverse events as related to the investigational therapy.
The side effects were thought to be related to the preparation for receiving the CRISPR therapy – to undergo treatment, patients had to be treated with chemotherapy to destroy their old bone marrow cells, which can cause adverse events.
“The data we announced today are remarkable and demonstrate that CTX001 has the potential to be a curative CRISPR/Cas9-based gene-editing therapy for people with sickle cell disease and beta thalassemia,” said Jeffrey Leiden (pictured left), president and chief executive officer of Vertex.
“We look forward to continuing to work with physicians, patients, caregivers and families over the coming months and years to bring forward the best possible therapy for these two serious diseases and to continue to accelerate our gene-editing programs for other serious diseases such as Duchenne muscular dystrophy and myotonic dystrophy type 1,” he added.
The CRISPR/Cas-9 method of gene editing allows precise alterations to DNA sequences of living cells on demand. The technology introduces a break in a specific place within DNA and triggers a self-repair mechanism. However, instead of restoring the original sequence, CRISPR serves as a new template that can be used to modify the sequence.
Vertex paid CRISPR Therapeutics $105m upfront in 2015, with up to $420m in milestone payments, to tap into its gene-editing expertise. CRISPR Therapeutics was founded by a team led by Emmanuelle Charpentier and Jennifer Doudna, who received awards for the discovery of the CRISPR/Cas9 method.
It then paid $175m upfront to expand this collaboration, with milestones that could drive the value of the deal above the $1bn mark.
Vertex is also looking at the possibility of using the CRISPR/Cas9 method to correct the mutations in the cystic fibrosis transmembrane conductance regulator (CTFR) gene that underpins the disease, as well as other contributing genes.
The American pharma giant also acquired Semma Therapeutics in September, which is focused on the use of stem cells as a potential cure for type 1 diabetes.