6 April 2023 - - US-based biotechnology company Vertex Pharmaceuticals Inc. (NASDAQ: VRTX) and Switzerland-based gene editing company CRISPR Therapeutics (NASDAQ: CRSP) have completed the rolling Biologics License Applications to the US Food and Drug Administration for the investigational treatment exagamglogene autotemcel (exa-cel) for sickle cell disease and transfusion-dependent beta thalassemia, the companies said.

The BLAs include requests for Priority Review, which if granted, would shorten the FDA's review of the application to eight months from the time of submission versus a standard review timeline of 12 months.

These submissions are supported by results from the ongoing Phase 3 studies, CLIMB-111 and CLIMB-121, as well as an ongoing long-term follow-up study, CLIMB-131.

Data from the Phase 3 studies were most recently presented at the American Society of Hematology annual meeting and Exposition in December of 2022.

In the US, exa-cel has been granted Regenerative Medicine Advanced Therapy, Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the FDA for both SCD and TDT.

In Europe, the Marketing Authorization Applications for exa-cel were submitted in December 2022 and validated by the European Medicines Agency and the Medicines and Healthcare products Regulatory Agency in January 2023.

In the EU, exa-cel has been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the EMA, for both SCD and TDT.

In the UK, exa-cel has also been granted an Innovation Passport under the Innovative Licensing and Access Pathway from the MHRA.

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 vaso-occlusive crises for patients with SCD and reduce or eliminate 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 ASH annual meeting and Exposition in December 2022.

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.

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 patients for up to 15 years after exa-cel infusion.

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 currently enrolling patients ages 5 to 11 years with a 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.

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.

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, 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.

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.

Exa-cel represents the first potential treatment to emerge from the joint research program.

Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialization of exa-cel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases.

The company has multiple approved medicines that treat the underlying cause of cystic fibrosis -- a rare, life-threatening genetic disease -- and has several ongoing clinical and research programs in CF.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London.

CRISPR Therapeutics is a gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA.

CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases.

CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned US subsidiary, CRISPR Therapeutics, Inc., and R&D operations in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom.