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CASGEVY™ (gene editing)

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  • Product Information

    Product Information

    Scientific name: exa-cel (exagamglogene autotemcel)
    Brand name: CASGEVY™
    RESPONSIBLE: Vertex Pharmaceuticals and CRISPR Therapeutics collaboration

  • Clinical Trial/Study Information

    Clinical Trial/Study Information

    CLIMB-Thal-111

    Trial Name: CLIMB-Thal-111
    Code: NCT03655678
    Phase: 1/2/3
    Eligible patient diagnosis: TDT – all genotypes (adult & paediatric/adolescent; ages 12 – 35)
    No. of Patients enrolled: 48 (Last update: 10/6/2023)
    Study Sites: 12 Sites per country

    Anticipated completion date: August 2024
    Scope of the Study / Aim: Transfusion independence for at least 12 consecutive months

    15 Years Follow-up Study

    Trial Name: Long-term follow-up study (CLIMB-131)
    Code: NCT04208529
    Phase: Long-term follow-up study of CLIMB-111 (TDT) & CLIMB-121 (SCD)
    Eligible patient diagnosis: TDT patients who participated in CLIMB-111 (ages 2 and older)
    No. of Patients enrolled: 114 [total anticipated] (Last update: 29/9/2023)
    Study Sites: 15 Sites per country

    Anticipated completion date: September 2039
    Scope of the Study / Aim: After completing the parent clinical study, patients will be followed for 15 years post infusion. Monitoring for malignancies, new or worsening haematologic disorders, serious adverse events, mortality

    CLIMB-161

    Trial Name: CLIMB-161
    Code: NCT05477563
    Phase: 3
    Eligible patient diagnosis: TDT – all genotypes & SCD (adult & paediatric/adolescent; ages 12 – 35)
    No. of Patients enrolled: 18 [total anticipated] (Last update: 7/7/2023)
    Study Sites: 5 Sites per country

    Completion date: February 2025
    Scope of the Study / Aim: Concentration of Total (Hb) and Fetal (HbF) for up to 12 months after infusion

    VX21-CTX001-141

    Trial Name: VX21-CTX001-141
    Code: NCT05356195
    Phase: 3
    Eligible patient diagnosis: TDT – all genotypes (paediatric; ages 2 -11)
    No. of Patients enrolled: 15 [anticipated] (Last update: 31/5/2023)
    Study Sites: 6 Sites per country

    Completion date: May 2026
    Scope of the Study / Aim: Safety & efficacy in children with TDT (Transfusion independence for at least 12 consecutive months)

  • Regulatory Information

    Regulatory Information

    Status: Authorised

    Additional notable points:

    • EMA: Orphan Drug Designation (2019), Priority Medicines (PRIME) designation (2021 – TDT); CHMP Positive Opinion for conditional approval (Dec 2023), conditional marketing authorisation for SCD and TDT patients 12 years and older (Feb 2024)
    • FDA: Fast Track Designation (2019), Regenerative Medicine Advanced Therapy (RMAT) designation (2020), Orphan Drug Designation (2020) ; BLA submission accepted for TDT & SCD (Jun 2023) – Approved for the treatment of TDT in patients 12 years and older (Jan 2024)
    • MHRA: Granted Innovation Passport (2023), Marketing Authorisation Application submitted in Jan. 2023 – Under review, Conditional approval for SCD and TDT in patients 12 years of age and older (Nov 2023)
    • NICE: Approved for use within the NHS for TDT patients 12 years and older (August 2024)
    • NHRA (Bahrain): Approved for the treatment of TDT and SCD (Dec 2023)
    • SFDA (Saudi Arabia): Approved for the treatment of TDT and SCD (Jan 2024)
    • Canada: Approved for the treatment of TDT and SCD (Sep 2024)
    • Switzerland: Approved for the treatment of SCD and TDT (Nov 2024)
    • United Arab Emirates: Approved for the treatment of SCD and TDT (Feb 2025)

Update: 31 March 2025

  • > 50 authorised treatment centres have been activated (Feb 2025)
  •  >50 patients have had a first cell collection to-date (Feb 2025)

Source: Vertex Reports Fourth Quarter and Full Year 2024 Financial Results | Vertex Pharmaceuticals

 

Update: 19 December 2024

  • Planned submissions in the UAE and Kuwait
  • 45 authorised treatment centres have been activated (mid-October 2024)
  • 40 patients have had a first cell collection to-date (Dec 2024)
  • Early Access Programme approved for TDT and SCD in Italy (4 November 2024)
  • Agreement with NHS England for reimbursement of treatment for TDT patients

New data

  • Data presented at the 66th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that:
    • A total of 56 patients with severe genotypes [β0/β0or β0/β0-like] had received exa-cel by the cut-off date of May 2024.
    • Of the 52 patients evaluable:
      – 49 (94.2%) achieved transfusion independence. On average transfusions were stopped 1.1 months after infusion. Transfusion independence was maintained for 32.4 months (on average)
      – For all patients, mean total Hb ≥12g/dL Month 5 onward and mean HbF was ≥ 11g/dL Month 5 onward
    • 44 patients completed 2 years of follow up

Sources: https://news.vrtx.com/news-releases/news-release-details/vertex-presents-positive-long-term-data-casgevytm-0
https://news.vrtx.com/news-releases/news-release-details/vertex-reports-third-quarter-2024-financial-results
Durable Clinical Benefits with Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia

 

Update: 30 September 2024

  • NICE (UK) has approved Casgevy for use in patients with thalassaemia aged 12 or older within the NHS, funded through the Innovative Medicines Fund.
  • 35 authorised treatment centers (ATCs) have been activated globally
  • Early Access Programmes for TDT and SCD implemented by the French National Health Authority (HAS)

Sources: https://www.england.nhs.uk/2024/08/gene-editing-therapy-that-could-cure-blood-disorder-thalassaemia-for-nhs-patients/
https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2024-financial-results

 

Update: 30 June 2024

Data presented at the 29th EHA Annual Congress (13-16 June 2024) in Madrid, Spain, showed that:

– A total of 54 patients with severe genotypes [β0/β0or β0/β0-like] had received exa-cel by the cut-off date of 18 September 2023.

    • Of the 45 patients evaluable:

– 42 (93.3%) achieved transfusion independence. On average transfusions were stopped 32.3 days after infusion. Transfusion independence was maintained for 27.7 months (on average)

– For all patients, total Hb was 11.5 g/dL at Month 3 (≥12g/dL Month 6 onward) and HbF was 7.9 g/dL at Month 3 (≥ 11g/dL Month 6 onward)

– 33 patients completed 2 years of follow up.

 

 

 

 

 

 

Source: exagamglogene autotemcel for transfusion-dependent beta-thalassaemia

 

Update: 31 March 2024

  • FDA: Approved for the treatment of TDT in patients 12 years and older (Jan 2024)
  • SFDA (Saudi Arabia): Approved for SCD and TDT in patients 12 years and older (Jan 2024)
    • 1st authorised treatment centre has been activated (Ministry of National Guard Health Affairs). The company is working to qualify additional hospitals (e.g. King Faisal Specialist Hospital).
  • EMA: conditional marketing authorisation for SCD and TDT patients 12 years and older (Feb 2024)
    • Patient eligibility is determined by recurrent VOCs (SCD) and suitability for HSCT for whom a matched donor is not available (TDT).
    • It is estimated that approx. 8,000 patients will potentially be eligible for treatment in the EU.
  • Authorised Treatment Centres: 12 in the US, 3 in EU and 1 in KSA are activated. Goal: 50 in the US, 25 in Europe and 2 in KSA.
  • Enrolment in phase 3 studies for patients with SCD and TDT aged 5 – 11 years is complete.

Sources: https://news.vrtx.com/news-releases/news-release-details/vertex-announces-approval-first-crisprcas9-gene-edited-therapy
https://www.businesswire.com/news/home/20240109040535/en/Vertex-Announces-Approval-of-First-CRISPRCas9-Gene-Edited-Therapy-CASGEVY%E2%84%A2-for-the-Treatment-of-Sickle-Cell-Disease-SCD-and-Transfusion-Dependent-Beta-Thalassemia-TDT-in-Kingdom-of-Saudi-Arabiahttps://news.vrtx.com/news-releases/news-release-details/european-commission-approves-first-crisprcas9-gene-edited
https://news.vrtx.com/news-releases/news-release-details/vertex-reports-fourth-quarter-and-full-year-2023-financial
https://news.vrtx.com/news-releases/news-release-details/vertex-announces-us-fda-approval-casgevytm-exagamglogene

 

Update: 20 December 2023

  • CHMP Positive Opinion for conditional approval (Dec 2023) – awaiting European Commission approval for Marketing Authorisation (estimated for Feb 2024)
  • MHRA (UK): Conditional approval for SCD and TDT in patients 12 years and older (Nov 2023)
  • NHRA (Bahrain): Approved for the treatment of SCD and TDT (Dec 2023)

New data

Data presented at the 65th ASH Annual Congress (9 – 12 December 2023) in San Diego (USA) showed that:

    • A total of 52 patients with with severe genotypes [β0/β0or β0/β0-like] had received exa-cel by the cut-off date of 16 January 2023.
    • Of the 35 patients evaluable (with more than 16 months follow up after exa-cel infusion – CLIMB THAL-111, phase 3), 32 (91.4%) achieved transfusion independence. On average transfusions were stopped 35.2 days after infusion. Transfusion independence was maintained for 22.5 months (on average). 1patient had a reduction of 83.9% in the annual RBC transfusion volume. 2 patients have been transfusion-free for 7.3 months and 4.0 months.
    • For all patients, total Hb was 11.4 g/dL at Month 3 (≥12g/dL Month 6 onward) and HbF was 7.7 g/dL at Month 3 (≥ 10 g/dL Month 6 onward)
    • Adults and adolescents infused with exa-cel reported sustained and clinically meaningful improvements in their quality of life with improvements observed across different instruments and domains, including physical, emotional, social/family and functional well-being and overall health status.

Sources: https://news.vrtx.com/news-releases/news-release-details/vertex-receives-chmp-positive-opinion-first-crisprcas9-gene
https://news.vrtx.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-announce-authorization-first
https://www.globenewswire.com/news-release/2023/12/02/2789644/0/en/CASGEVY-Gets-Bahrain-approval-for-treatment-marking-it-second-country-in-the-world.html
https://news.vrtx.com/news-releases/news-release-details/positive-results-pivotal-trials-casgevytm-exagamglogene
https://ash.confex.com/ash/2023/webprogram/Paper179916.html
https://ash.confex.com/ash/2023/webprogram/Paper190534.html

 

Update: 30 September 2023

  • Investigation in gentler conditioning for exa-cel is underway.

Source: https://news.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2023-financial-results

 


Update: 30 June 2023

FDA Submission
• BLA application submitted to FDA (3 April 2023) for exa-cel for patients with SCD and TDT. The submission is based on the results of the ongoing Phase 3 studies, CLIMB-111 and CLIMB-121, as well as an ongoing long-term follow-up study, CLIMB-131.
• FDA has accepted Priority Review for BLA submission and set a PDUFA (the date by which the FDA must respond to the application) target date of 30 March 2024.

Trial Progress
• Dosing in the Phase 1/2/3 CLIMB-111 and CLIMB-121 studies continues, as does the CLIMB-131 long-term follow-up study in patients 12 years of age and older.
• Two additional Phase 3 studies of exa-cel continue to enroll patients 5 to 11 years of age with TDT or SCD.

New data
Data presented at the 28th EHA Annual Congress (9 – 11 June 2023) in Frankfurt (Germany) showed that:

▪ Of the 48 patients with TDT who had received exa-cel at the time of the analysis, 58.3% have genotypes associated with severe disease, beta-zero/beta-zero or other beta-zero-like severe genotypes.
▪ 27 TDT patients who were evaluable:
o 24/27 (88.9%) achieved the primary endpoint of transfusion independence for at least 12 consecutive months
o Mean duration of transfusion-independence was 20.5 months with a maximum of 40.7 months.
o All patients who received exa-cel, mean total hemoglobin was ≥11g/dL at Month 3 and ≥12g/dL from Month 6 onward.

Sources: https://www.businesswire.com/news/home/20230402005036/en/
https://investors.vrtx.com/news-releases/news-release-details/vertex-and-crisprtherapeutics-complete-submission-rolling
https://investors.vrtx.com/news-releases/news-release-details/fda-accepts-biologicslicense-applications-exagamglogene
https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-firstquarter-2023-financial-results
https://investors.vrtx.com/news-releases/news-release-details/positive-resultspivotal-trials-exa-cel-transfusion-dependent


Update: 31 March 2023

  • The Phase 1/2/3 CLIMB-111 and CLIMB-121 studies and the CLIMB-131 long-term follow-up study are ongoing in patients 12 years of age and older.
  • Two additional Phase 3 studies of exa-cel in pediatric patients with TDT and SCD continue to enroll patients.

Source: https://news.vrtx.com/news-releases/news-release-details/vertex-reports-fourthquarter-and-full-year-financial-2022

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