FDA Accepts Exa-cel BLA for Sickle Cell and Transfusion-Dependent β-Thalassemia


CRISPR Therapeutics and Vertex Pharmaceuticals completed their rolling submissions in April 2023.

The FDA has accepted Vertex Pharmaceuticals’ biologics license application (BLA) for exagamglogene autotemcel (exa-cel) for treating severe sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT).1

The FDA has granted Priority Review for SCD with a Prescription Drug User Fee Act (PDUFA) target action date of December 8, 2023, and Standard Review for TDT with a PDUFA target action date of March 30, 2024. The BLAs are supported by data from 2 ongoing phase 3 clinical trials—CLIMB-111 (NCT03655678) in TDT and CLIMB-121 (NCT03745287) in SCD—as well as a long-term follow-up study—CLIMB-131 (NCT04208529)—that includes patients with both disorders. Updated data from the studies will be presented at the European Hematology Association (EHA) 2023 Congress, held June 8-11, both virtually and in Frankfurt, Germany.

“We are very pleased with the acceptance of the submissions and the Priority Review designation for SCD by the FDA, as well as the progress of the exa-cel filings in the EU and U.K.,” Reshma Kewalramani, MD, chief executive officer and president, Vertex, said in a statement.1 “Exa-cel holds the promise to be the first CRISPR gene-editing therapy to be approved, and we continue to work with urgency to bring this treatment with transformative potential to patients who are waiting.”

Vertex, along with its collaborator CRISPR Therapeutics, completed the rolling BLA submissions for exa-cel in both indications in April 2023.2 The companies alsosubmitted marketing authorization applications for exa-cel to the European Medicines Agency and Medicines and Healthcare products Regulatory Agency in December 2022 and January 2023, respectively.

READ MORE: ICER Reports Sickle Cell Gene Therapy Cost Effective at $1.9 Million

Prior to the upcoming EHA data, the most recent data, with a cutoff date of February 2022, were presented at the American Society of Hematology 2022 meeting. In CLIMB-121, among patients with SCD aged 12 to 35 years, 31 individuals had been infused with exa-cell (mean follow-up, 9.6 months), of whom 19.4% (n = 6) were between 12 and 17 years old and 93.5% (n = 29) had the βs/βs genotype.3 In the 2 years prescreening, patients had experienced 3.9 severe vaso-occlusive crises (VOCs) per year (range, 2.0-9.5). At the time of the data cut after exa-cel infusion, though, all patients were VOC-free (follow-up range, 2.0-32.3 months post infusion).3

“We are glad to see that the unmet need and urgency for innovative therapies in SCD was recognized by the FDA with Priority Review,” Samarth Kulkarni, PhD, chief executive officer, CRISPR Therapeutics, added.1 “This is an exciting milestone for the CRISPR platform, and we look forward to continuing the close collaboration with our partners at Vertex to bring this medicine to patients in need.”

1. FDA accepts Biologics License Applications for exagamglogeneautotemcel (exa-cel) for severe sickle cell disease and transfusion-dependent Beta thalassemia. News release. Vertex Pharmaceuticals. June 8, 2023. Accessed June 9, 2023.https://investors.vrtx.com/news-releases/news-release-details/fda-accepts-biologics-license-applications-exagamglogene
2. Vertex and CRISPR Therapeutics Complete Submission of Rolling Biologics License Applications (BLAs) to the US FDA for exa-cel for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia. News release. Vertex Pharmaceuticals Inc; CRISPR Therapeutics. April 3, 2023. Accessed June 9, 2023. https://www.businesswire.com/news/home/20230402005036/en/
3. Frangoul H, Locatelli F, Bhatia M, et al. Efficacy and Safety of a Single Dose of ExagamglogeneAutotemcel for Severe Sickle Cell Disease. Presented at: 64th ASH Annual Meeting, December 10-13, 2022. Oral Abstract #12. https://ash.confex.com/ash/2022/webprogram/Paper162353.html
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