Vertex and CRISPR Therapeutics Present New Data in 22 Patients With Greater Than 3 Months Follow-Up Post-Treatment With Investigational CRISPR/Cas9 Ge

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13/06/2021 15:29
- Beta thalassemia: All 15 patients were transfusion independent after CTX001 infusion -
- Sickle cell disease: All seven patients were free of vaso-occlusive crises after CTX001 infusion -

BOSTON & ZUG, Switzerland & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 11, 2021-- Vertex Pharmaceuticals Incorporated (Nasdaq:VRTX) and CRISPR Therapeutics (Nasdaq:CRSP) today announced new data on 22 patients, with follow-up of at least 3 months, and ranging from 4 months to 26 months, treated with the investigational CRISPR/Cas9-based gene-editing therapy, CTX001, that show a consistent and sustained response to treatment. CTX001 is being investigated in two ongoing Phase 1/2 clinical trials as a potential one-time therapy for patients suffering from transfusion-dependent beta thalassemia (TDT) and severe sickle cell disease (SCD). In total, more than 40 patients have been dosed across both studies to date.


All 15 patients with TDT, including six who have the beta zero/beta zero or other severe genotypes, were transfusion-free at last follow-up, and all seven patients with severe SCD were free of vaso-occlusive crises (VOCs) from CTX001 infusion through last follow-up. Five patients with TDT and two patients with SCD now have follow-up of greater than one year, demonstrating a stable and durable response to treatment. These data are available as e-posters beginning on June 11, 2021, at 09:00 CEST, and a partial presentation of these data were presented during the Joint EHA-ASH Symposium on June 10, 2021 from 17:30-18:30 CEST. A summary of the results from the CLIMB-111 and CLIMB-121 Phase 1/2 clinical trials is provided below.

“The data presented today in 22 patients are impressive in both the consistency and durability of effect. These results add to the growing body of evidence that CTX001 may hold the promise for a one-time functional cure for sickle cell disease and beta thalassemia. We are working with urgency to complete enrollment and look forward to finalizing regulatory discussions and moving towards filing,” said Reshma Kewalramani, M.D., Chief Executive Officer and President at Vertex.

“The continued progress and momentum of CTX001 validate the role that CRISPR gene-editing technology could have in the future of therapeutics,” added Samarth Kulkarni, Ph.D., Chief Executive Officer at CRISPR Therapeutics. “We are excited about these results and look forward to additional longer-term data and to moving this investigational medicine forward for a larger population of patients with these two devastating diseases.”

“As a physician caring for patients suffering from beta thalassemia, I have a high sense of urgency for novel and efficacious treatments,” said Dr. Franco Locatelli, Professor of Pediatrics at the Sapienza University of Rome, Director of the Department of Pediatric Hematology and Oncology at Bambino Gesù Children’s Hospital. “These results suggest the potential for a durable benefit for patients with transfusion-dependent beta thalassemia.”

“It is thrilling to work on a groundbreaking program like CTX001,” said Dr. Stephan Grupp, Section Chief, Cellular Therapy and Transplant, Division of Oncology, Children's Hospital of Philadelphia. “This approach uses CRISPR/Cas9 gene editing to enable the patient’s own cells to produce fetal hemoglobin, and to see results that demonstrate the potential for a treatment that may transform the lives of many patients is an exciting time for me and the team.”

CLIMB-111 Trial in TDT: Updated Results
The 15 patients with TDT reported at EHA are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All 15 patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin, fetal hemoglobin and transfusion independence.

All 15 patients were transfusion independent with follow-up ranging from 4 to 26 months after CTX001 infusion and had clinically meaningful improvements in total hemoglobin from 8.9 to 16.9 g/dL and fetal hemoglobin from 67.3% to 99.6% at last visit.

Bone marrow allelic editing data collected from 10 patients with at least 6 months of follow-up, of which five patients had at least 12 months of follow-up and one patient had at least 24 months of follow-up, demonstrated a durable effect.

The safety data from all 15 patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. As previously reported, there were four serious adverse events (SAEs) considered related or possibly related to CTX001 reported in one patient: headache, hemophagocytic lymphohistiocytosis (HLH), acute respiratory distress syndrome and idiopathic pneumonia syndrome. All four SAEs occurred in the context of HLH and have resolved. The majority of non-serious adverse events were considered mild to moderate.

The presentations at EHA and the data summarized in this press release cover all TDT patients dosed with CTX001 with three or more months of follow-up as of the data cut on March 30, 2021. In addition to the data presented above, a TDT patient, with less than three months of follow-up and therefore not included in the data cut, experienced an SAE; this SAE of cerebellar hemorrhage, which was considered related to busulfan conditioning, has resolved.

Enrollment and dosing are ongoing.

CLIMB-121 Trial in Severe SCD: Updated Results
The seven patients reported at EHA are patients who had reached at least three months of follow-up after CTX001 dosing and therefore could be assessed for initial safety and efficacy. All seven patients showed a similar pattern of response, with rapid and sustained increases in total hemoglobin and fetal hemoglobin, as well as elimination of VOCs.

All seven patients remained VOC-free with follow-up ranging from five to 22 months after CTX001 infusion and had clinically meaningful improvements in total hemoglobin from 11 to 15.9 g/dL and fetal hemoglobin levels from 39.6% to 49.6% at last visit.

Bone marrow allelic editing data collected from four patients who have at least six months of follow-up, of which two had 12 months of follow-up, demonstrated a durable effect.

The safety data from all seven patients were generally consistent with an autologous stem cell transplant and myeloablative conditioning. There were no SAEs considered related to CTX001, and the majority of non-serious adverse events were considered mild to moderate.

Enrollment and dosing are ongoing.

About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate or eliminate transfusion requirements for patients with TDT and reduce or eliminate painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

About the Gene-Editing Process in These Trials
Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.

About the Vertex-CRISPR Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics.



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