On December 10, 2022 CRISPR Therapeutics (Nasdaq: CRSP) and Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported an oral, encore presentation of clinical data from patients with sickle cell disease (SCD) or transfusion-dependent beta-thalassemia (TDT) treated with the investigational therapy exagamglogene autotemcel (exa-cel) in CLIMB-111 or CLIMB-121 and followed in CLIMB-131, a long-term follow-up study (Press release, CRISPR Therapeutics, DEC 10, 2022, View Source [SID1234625015]). Vertex will also present new health economics and outcomes research from multiple studies in patients with SCD and TDT.

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"We are excited to be at ASH (Free ASH Whitepaper) and share data from the pivotal exa-cel trials and from multiple real-world studies examining the burden of severe SCD and TDT," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. "We remain on track to complete submission of the first ever CRISPR-based therapy in the EU and U.K. this year, and we have initiated our rolling submission in the U.S., which we plan to complete in Q1 2023. We are working with urgency to bring forward this potential therapy to patients who are waiting."

Vertex will have the following presentations at ASH (Free ASH Whitepaper) this year.

Oral presentation, abstract #12 combined with abstract #2137, in partnership with CRISPR Therapeutics, entitled "Efficacy and Safety of a Single Dose of Exagamglogene Autotemcel for Transfusion-Dependent Beta-Thalassemia and Severe Sickle Cell Disease," will be presented on Saturday, December 10 at 10:45 a.m CST. The presentation will include encore data as presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022 on patients with SCD or TDT who received the investigational therapy exa-cel in the CLIMB-111 or CLIMB-121 study and were followed in CLIMB-131, a long-term follow-up study.
Oral presentation, abstract #577, entitled "Health-Related Quality of Life, Disease Impacts, and Health Equity Concerns in Adults with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises: Preliminary Results from a Global Longitudinal Survey," will be presented on Sunday, December 11 at 12:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with SCD with recurrent vaso-occlusive crises (VOCs). This presentation represents preliminary results from an ongoing longitudinal study.
Poster presentation, abstract #4820, entitled "Clinical and Economic Outcomes in Patients with Transfusion-Dependent Beta-Thalassemia and Patients with Sickle Cell Disease with Recurrent Vaso-Occlusive Crises Receiving Hematopoietic Stem Cell Transplants in the United States," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study analyzes the demographics, transplant-related complications and costs of patients with SCD and TDT who undergo a hematopoietic stem cell transplant (HSCT) in the United States utilizing a claims database.
Poster presentation, abstract #4882, entitled "Health-Related Quality of Life and Disease Impacts in Adults with Transfusion-Dependent Beta-Thalassemia: Preliminary Results from the Global Longitudinal Survey," will be presented on Monday, December 12 from 6:00-8:00 p.m. CST. The study quantifies the symptoms, quality of life and work impacts of living with TDT. This presentation represents preliminary results from an ongoing longitudinal study.
The accepted abstracts are available online on the ASH (Free ASH Whitepaper) website.

About exagamglogene autotemcel (exa-cel)

Exa-cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients with SCD or TDT, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa-cel has the potential to reduce or eliminate painful and debilitating VOCs for patients with SCD and alleviate transfusion requirements for patients with TDT. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021 and presented at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress in June 2022.

Based on progress in this program to date, exa-cel 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 SCD and TDT. Exa-cel 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 SCD and TDT.

The companies have begun the rolling Biologics License Application (BLA) submission for exa-cel to the U.S. FDA and plan to complete the BLA by the end of the first quarter 2023 and remain on track to submit exa-cel to the Medicines and Healthcare products Regulatory Agency in the U.K. and the EMA in the European Union by the end of the year.

About CLIMB‑111 and CLIMB‑121

The ongoing Phase 1/2/3 open-label trials, CLIMB‑111 and CLIMB‑121, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa-cel infusion. Each patient will be asked to participate in CLIMB‑131, a long-term follow-up trial.

About CLIMB-131

The ongoing long-term, open-label trial, CLIMB-131, is designed to evaluate the safety and efficacy of exa-cel in patients who received exa-cel in CLIMB‑111, CLIMB‑121, CLIMB‑141, CLIMB‑151 or CLIMB-161. The trial is designed to follow participants for up to 15 years after exa-cel infusion.

About CLIMB‑141 and CLIMB‑151

The ongoing Phase 3 open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years and will plan to extend to ages 2 to less than 5 years at a later date. Each trial will enroll approximately 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

About CLIMB-161

The ongoing Phase 3b study, CLIMB-161, is to support expansion of our manufacturing footprint after initial potential approval and launch. This study will enroll approximately 12 patients with either SCD or TDT ages 12 to 35 years. Patients will be followed for approximately one year after infusion. Each patient will be asked to participate in CLIMB-131, a long-term follow-up trial.

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, exa-cel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exa-cel. 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 exa-cel on multiple measures of disease and for safety.