CRISPR Therapeutics (NASDAQ: CRSP) and Vertex Pharmaceuticals Incorporated (NASDAQ: VRTX) today announced positive, interim data from the first two patients with severe hemoglobinopathies treated with the investigational CRISPR/Cas9 gene-editing therapy CTX001 in ongoing Phase 1/2 clinical trials. One patient with transfusion-dependent beta thalassemia (TDT) received CTX001 in the first quarter of 2019 and data for this patient reflect nine months of safety and efficacy follow-up. One patient with severe sickle cell disease (SCD) received CTX001 in mid-2019 and data for this patient reflect four months of safety and efficacy follow-up. These studies are ongoing and patients will be followed for approximately two years following infusion. Several additional patients have been enrolled and have had drug product manufactured across the two studies.

Transfusion-Dependent Beta Thalassemia The patient with TDT has the β0/IVS-I-110 genotype and required 16.5 transfusions per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil engraftment 33 days after CTX001 infusion and platelet engraftment 37 days after infusion. Two serious adverse events (SAEs) occurred, neither of which the principal investigator (PI) considered related to CTX001: pneumonia in the presence of neutropenia and veno-occlusive liver disease attributed to busulfan conditioning; both subsequently resolved. At nine months after CTX001 infusion, the patient was transfusion independent and had total hemoglobin levels of 11.9 g/dL, 10.1 g/dL fetal hemoglobin, and 99.8% F-cells (erythrocytes expressing fetal hemoglobin).

Sickle Cell Disease The patient with SCD experienced seven vaso-occlusive crises (VOCs) per year (annualized rate during the two years prior to consenting for the study) before enrolling in the clinical study. The patient achieved neutrophil and platelet engraftment 30 days after CTX001 infusion. Three SAEs occurred, none of which the PI considered related to CTX001: sepsis in the presence of neutropenia, cholelithiasis, and abdominal pain, all of which resolved. At four months after CTX001 infusion, the patient was free of VOCs and had total hemoglobin levels of 11.3 g/dL, 46.6% fetal hemoglobin, and 94.7% F-cells (erythrocytes expressing fetal hemoglobin).

“We are very encouraged by these preliminary data, the first such data to be reported for patients with beta thalassemia and sickle cell disease treated with our CRISPR/Cas9 edited autologous hematopoietic stem cell candidate, CTX001,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “These data support our belief in the potential of our therapies to have meaningful benefit for patients following a one-time intervention. We continue to enroll these studies as we drive forward to develop CRISPR/Cas9 therapies as a new class of transformative medicines to treat serious diseases.”

“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, M.D., Ph.D., Chairman, President and Chief Executive Officer of Vertex. “While the data are exciting, we are still in the early phase of this clinical program. 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.”