Vertex and CRISPR Submit BLA for Sickle Cell Disease Treatment

On April 3, 2023, Vertex Pharmaceuticals and CRISPR Therapeutics announced that they submitted Biological License Applications (BLAs) for an investigational treatment using exagamglogene autotemcel (exa-cel) for sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).

“The completion of our exa-cel global regulatory filings is a historic milestone,” said Carmen Bozic, MD, Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex Pharmaceuticals in the press release. “We want to thank the clinical trial participants and the sickle cell and beta thalassemia communities, as well as the physicians, nurses, coordinators, caregivers, and friends who support them.”

SCD is a genetic condition that causes abnormally shaped red blood cells, leading to complications like stroke, visual changes, infections, and pain crises. Despite impacting 20 million people globally, the condition’s only approved treatment is a bone marrow transplant.

TDT has a similarly complicated treatment protocol, requiring regular blood transfusions to offset the reduced hemoglobin levels caused by the condition.

Beyond invasive procedures, TDT and SCD treatments can be costly and recurring, leading to inequities in healthcare access.

Exa-cel, once known as CTX001, uses CRISPR technology to edit a patient’s hematopoietic stem cells, allowing them to produce high fetal hemoglobin levels. The treatment has been shown to minimize Vaso-occlusive crises in SCD patients and minimize the need for transfusion in TDT patients.

In June 2022, the companies released data from clinical trials at the European Hematology Association Congress. The earlier study was a small-scale clinical trial that recruited 75 patients with SCD or TDT. The clinical trial confirmed the safety of the treatment and provided insight into the efficacy of the gene-editing technology for SCD and TDT.

Data from multiple ongoing clinical trials back the application submitted to the FDA. CLIMB-111 and CLIMB-121 are phase 3 clinical trials that test a single dose of exa-cel in individuals with TDT or SCD who are between 12 and 35. Each of these trials plans to follow patients for two years.

After the two-year monitoring period, participants will be asked to enlist in CLIMB131, an ongoing long-term, open-label follow-up study. Participants will be monitored over 15 years to understand the long-term effects and efficacy of the exa-cel treatment.

Although a standard BLA review takes one year, the companies have applied for priority review, meaning this treatment could be on the market in eight months.

“Within a decade, we have progressed from the discovery of the CRISPR platform to the first regulatory filings for a CRISPR-based therapy, which speaks to the transformative nature of CRISPR technology,” said Phuong Khanh (P.K.) Morrow, MD, FACP, Chief Medical Officer at CRISPR Therapeutics, in the press announcement.