Canada Approves Vertex and CRISPR Therapeutics’ Gene Therapy Casgevy for Sickle Cell Disease and TDT

Health Canada has granted marketing authorization to Vertex Pharmaceuticals' and CRISPR Therapeutics’ autologous gene-edited cell therapy exagamglogene autotemcel (exa-cel), marketed under the name Casgevy, for the treatment of sickle cell disease (SCD) in patients aged 12 years and older with recurrent vaso-occlusive crises (VOCs) and patients aged 12 years and older with transfusion-dependent beta thalassemia (TDT).¹

"Casgevy's approval is an exciting moment for 2 patient communities that have long awaited an innovative therapy that brings new hope and possibilities for those in need," Kevin Kuo, MD, hematologist and clinician investigator in the Red Blood Cell Disorders Clinic at University Health Network, and principal investigator for the CLIMB-131 clinical program (NCT04208529).¹

The approvals were based on data from the ongoing phase 1/2/3 CLIMB-121 clinical trial (NCT03745287), which is being conducted exclusively in patients with SCD, and the ongoing phase 1/2/3 CLIMB-111 clinical trial (NCT03655678),which is in patients with TDT; both trials are taking place at sites in multiple countries, including Canada. The primary end point for CLIMB-121, freedom from severe VOCs for 12 consecutive months, was met. Likewise, the primary end point for CLIMB-111, transfusion independence for 12 consecutive months, was also met. Vertex characterized the safety profile of the treatment as generally consistent with myeloablative conditioning using busulfan and hematopoietic stem cell transplant.

"Today's marketing authorization for Casgevy as Canada's first CRISPR-based gene-editing therapy is a historic moment," Michael Siauw, MS, general manager at Vertex Pharmaceuticals (Canada) Incorporated, said in a statement.¹ "We are excited for the potential of this one-time therapy for eligible SCD and TDT patients and are working closely with provincial, territorial, and federal governments to facilitate access as rapidly as possible."

Exa-cel was previously approved in the United States for a similar SCD indication on December 8, 2024.² The FDA’s decision was based on results from CLIMB-121 and the phase 3 long-term follow-up study CLIMB-131, which includes both patients with SCD and patients with TDT. Notably, the therapy was approved by the FDA in SCD simultaneously with bluebird bio's lovotibeglogene autotemcel (lovo-cel), marketed as Lyfgenia. A gene-edited cell therapy modified with the use of a lentiviral vector, lovo-cel was approved for the treatment for SCD in patients aged 12 years and older who have a history of vaso-occlusive events.

Exa-cel's approval in the US for TDT came slightly later, on January 16, 2024.³ The approval was based on data from CLIMB-111 and CLIMB-131. In CLIMB-111, 39 of 42 evaluable patients (93%) were free of the need for a red blood cell (RBC) transfusion for 12 months or more posttreatment. Furthermore, the 3 patients who did not achieve this end point demonstrated a greater than 70% decrease in necessitation of RBC transfusions.

Earlier this year, CGTLive® spoke with several experts about how doctors and other healthcare providers should help patients and families decide on a treatment path for SCD in light of the growing number of options available. Mark Walters, MD, a professor in residence for pediatrics at the Sickle Cell Center of Excellence at the University of California, San Francisco, was one of those who offered his viewpoint.

“Doctors and comprehensive healthcare teams will play a principal role in the decision-making process for patients considering the autologous gene therapies that are now approved and available,” Walters told CGTLive. “This involves carefully balancing the risks and benefits of the treatment, both in the short-term and the long-term, and understanding there's a potential for long-term side effects that aren't very well or are not understood at all right now that will have to be considered when making a decision about whether to pursue them.”

REFERENCES
1. Health Canada grants marketing authorization of first CRISPR/Cas9 gene-edited therapy, CASGEVY (exagamglogene autotemcel), for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. News release. Vertex Pharmaceuticals Incorporated. September 25, 2024. Accessed September 27, 2024. https://firstwordpharma.com/story/5898986.
2. FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. News release. FDA. December 7, 2023. Accessed December 7, 2023. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
3. Vertex Announces US FDA Approval of CASGEVY™ (exagamglogene autotemcel) for the Treatment of Transfusion-Dependent Beta Thalassemia. News release. January 16, 2024. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-casgevytm-exagamglogene