CASGEVY™ (gene editing)

Update: 30 June 2026

• Reimbursement agreement reached with GKV-Spitzenverband (Germany) for TDT and SCD
• >500 patient initiations since launch (May 2026)
• In 2026 (May 2026):
o Approx. 71 patients have had a first cell collection
o 24 patients have been infused
o 156 patients have started apheresis
• Gentler conditioning continues to be explored.
• Data presented at the EHA Annual Congress (11 – 14 June 2026) showed that:

1. CLIMB-151 (phase 3 clinical trial for children ages 2 – 11 with SCD):
• 11 patients have been dosed with CASGEVY
• All (8/8) patients with sufficient follow-up achieved the primary endpoint of being free from vaso-occlusive crises (VOCs) for at least 12 consecutive months. The mean duration of VOC-free was 19 months.
• No patient experienced a VOC following infusion with CASGEVY.
• All SCD pts had β S /β S genotype
• 72.7% of SCD pts (8/11) required ≤2 mobilization cycles
• The safety profile of CASGEVY in younger patients is consistent with myeloablative conditioning and autologous transplant in both SCD and TDT, as established in clinical studies in older patients.

Regulatory submissions in the USA, Saudi Arabia and UK have been completed to expand the use of Casgevy to younger children (currently authorised for ages 12 and older). The FDA awarded Vertex a Commissioner’s National Priority Voucher for pediatric submission, indicating an accelerated timeline for review once the submission is accepted.

Sources: First Quarter 2026 Financial Results
Vertex Announces CASGEVY® Reimbursement Agreement for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia in Germany | Vertex Pharmaceuticals Newsroom
Vertex Presents New Data on CASGEVY®, Including First European Presentation of Data in Children Ages 5–11, at the European Hematology Association Congress and Announces Additional Global Regulatory Submissions | Vertex Pharmaceuticals Newsroom
Long-Term Follow-Up Confirms Durable Clinical Benefits of Exagamglogene Autotemcel In Transfusion-Dependent B-Thalassaemia: Final Results Of The Climb Thal-111 Study

Update: 31 March 2026

In 2025, 301 thalassaemia and SCD patients started, 147 had their 1^st cell collection, and 64 were infused.

Sources: Fourth Quarter and Full Year 2025 Financial Results
Vertex Provides Pipeline and Business Updates in Advance of Upcoming Investor Meetings | Vertex Pharmaceuticals Newsroom

Update: 22 December 2025

• 165 patients have had a first cell collection until 30^th September 2025, including 50 patients in Q3 of 2025; 39 patients have been infused (10/39 in Q3 of 2025) (3 November 2025)
• Data presented at the 67^th ASH Annual Congress (6 – 9 December 2025) in Orlando (USA) showed that:

1. CLIMB-151 (phase 3 clinical trial for children ages 2 – 11 with SCD):

• • 11 patients have been dosed with CASGEVY
  • All SCD pts had β S /β S genotype
  • 80% of SCD pts (8/10) required ≤2 mobilization cycles
  • All (4/4) patients with sufficient follow-up achieved the primary endpoint of being free from vaso-occlusive crises (VOCs) for at least 12 consecutive months
  • No patient experienced a VOC following infusion with CASGEVY, with the longest duration of VOC-free of approximately two years (range 3.2–24.1 months)
  • The safety profile of CASGEVY in younger patients is consistent with myeloablative conditioning and autologous transplant in both SCD and TDT, as established in clinical studies in older patients.
  • Consistent with studies in older patients, children treated with CASGEVY have durable increases in fetal hemoglobin (HbF) and stable allelic editing.

2. CLIMB-121 (phase 1/2/3 clinical trial for SCD patients aged 12 – 35) or CLIMB-131 (long-term follow-up):

• 100% of patients (45/45) were VOC-free for 12 months, with a mean duration of VOC-free for 35.3 months (range 12.9–67.7 months)

Sources: Vertex Reports Third Quarter 2025 Financial Results | Vertex Pharmaceuticals Newsroom
Vertex Presents New Data on CASGEVY®, Including First-Ever Data in Children Ages 5-11 Years, at the American Society of Hematology Annual Meeting and Announces Plan for Global Regulatory Submissions | Vertex Pharmaceuticals Newsroom
First results of exagamglogene autotemcel in pediatric patients aged 5-11 years with transfusion-dependent β-thalassemia or sickle cell disease with recurrent severe vaso-occlusive crises

Update: 30 September 2025

• Reimbursement agreements with Italy and Denmark
• > 75 authorised treatment centres have been activated (Aug 2025)
• 115 patients have had a first cell collection to date; 29 patients have been infused (16/29 in Q2 of 2025) (30 June 2025)

Source: Vertex Announces CASGEVY® Reimbursement Agreement for the Treatment of Transfusion-Dependent Beta Thalassemia and Sickle Cell Disease in Italy | Vertex Pharmaceuticals Newsroom

Update: 30 June 2025

• Reimbursement agreement with NHS England for SCD. Similar agreement for TDT and SCD patients in Wales.
• Reimbursement agreements with Austria, Bahrain, England, the Kingdom of Saudi Arabia, Northern Ireland, Scotland, the United Arab Emirates, the United States, and Wales
• > 65 authorised treatment centres have been activated (May 2025)
• 90 patients have had a first cell collection to date (May 2025)
• Enrolment completed for paediatric trials in SCD and TDT.
• Gentler conditioning continues to be explored.

Data presented at the 30^th EHA Annual Congress (12 – 15 June) in Milan, Italy showed that:

• • 44/45 patients who had received exa-cel were free from VOCs for a mean duration of 35 months
  • Follow-up extends more than 5.5 years for SCD patients.

Sources: Vertex Reports First Quarter 2025 Financial Results | Vertex Pharmaceuticals
Vertex Presents Longer-Term Data at the 2025 European Hematology Association (EHA) Congress Demonstrating Durability of CASGEVY® and Provides Update on Expanding Global Access to CASGEVY | Vertex Pharmaceuticals

Update: 31 March 2025

Reimbursement agreement reached with NHS England for eligible SCD patients.

Source: Vertex Announces CASGEVY® Reimbursement Agreement for the Treatment of Sickle Cell Disease in England | 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)
• Commercial discussions with NHS England for access for patients with SCD

New data:

Data presented at the 66^th ASH Annual Congress (7 – 10 December 2024) in San Diego (USA) showed that:

• • A total of 46 patients were infused at the cut-off (May 2024).
  • Median follow-up of 29.9 months; 31 patients completed 2 years of follow-up.
  • 90% were VOC-free for more than 12 consecutive months post-infusion; the mean VOC-free duration was 29.3 months.
  • 95% were hospitalisation-free for more than 12 consecutive months post-infusion.
  • All patients maintained increased levels of Hb (mean total Hb 11.9g/dL from Month 3).

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 Severe Sickle Cell Disease

Update: 30 September 2024

• 35 authorised treatment centres (ATCs) have been activated globally
• Early Access Programmes for TDT and SCD implemented by the French National Health Authority (HAS)

Source: https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2024-financial-results

Update: 30 June 2024

Data presented at the 29^th EHA Annual Congress (13 – 16 June 2024) in Madrid (Spain) from the CLIMB SCD-121 phase 3 trial showed that:

• • A total of 46 patients with SCD had received exa-cel by the cut-off date of 18 September 2023.
  • The median follow-up was 22.3 months, with 17 patients completing 2 years of follow-up, and enrolling in the long-term follow-up study (CLIMB-131) involving 15 years of follow-up.
  • Of the 31 patients evaluable,
    • 29 (93.5%) were VOC-free for ≥12 consecutive months
    • 31 (100%) were free from VOC hospitalisations for ≥12 consecutive months.

Source: Exagamglogene Autotemcel for Severe Sickle Cell Disease

Update: 31 March 2024

• SFDA (Saudi Arabia): Approved for SCD and TDT in patients 12 years and older (Jan 2024)
  • 1^st 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 approximately 8,000 patients will potentially be eligible for treatment in the EU.
• Draft guidance, published on 14 March 2024, said the NICE committee considered the cost-effectiveness estimate for Casgevy to be higher than what NICE normally considers to be an acceptable use of NHS resources.
• Authorised Treatment Centres: 12 in the US, 3 in the 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://pharmaceutical-journal.com/article/news/gene-editing-sickle-cell-drug-not-approved-for-nhs-use-in-draft-nice-guidance
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-Arabia
https://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

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)
• FDA: Approved for the treatment of sickle cell disease (SCD) in patients aged 12 years and older (Dec 2023)
• NHRA (Bahrain): Approved for the treatment of SCD and TDT (Dec 2023)
• A list price of $2.2 million in the USA has been announced.

New data

• Data presented at the 65^th ASH Annual Congress (9–12 December 2023) in San Diego (USA) showed that:
  • The CLIMB SCD-121 trial met primary and key secondary endpoints, with exa-cel treatment resulting in early and sustained increases in Hb and HbF, leading to elimination of VOCs in 95% of pts, elimination of inpatient hospitalization for VOCs in 100% of patients and improved QOL. Safety profile of exa‑cel was generally consistent with myeloablative busulfan conditioning and autologous transplantation.
  • A total of 42 patients with SCD had received exa-cel by the cut-off date of 10 February 2023.
  • Of the evaluable patients:
    • 19/20 (95.0%) were free of VOCs for ≥12 consecutive months with an average VOC-free period of 21.8 months
    • 20/20 (100%) were free from hospitalizations for VOCs for≥12 consecutive months
    • 29/30 (96.7%) were free of VOCs for ≥9 consecutive months
    • For all patients, total Hb was 12.1 g/dL at Month 3 and was maintained at ≥11.0 g/dL from Month 6 onward; HbF was 36.0% at Month 3 and was generally maintained at ≥ 40.0% from Month 6 onward
  • 36/39 pts with ≥60 days follow-up after last RBC transfusion (including those not yet evaluable) remained VOC free (up to 41.4 months). Quality-of-life (QOL) measures showed clinically significant improvements.

Sources: https://www.reuters.com/business/healthcare-pharmaceuticals/vertexcrispr-price-sickle-cell-disease-gene-therapy-22-mln-2023-12-08/
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.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
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/Paper190139.html

Update: 30 September 2023

• FDA plans to hold an advisory committee meeting for exa-cel (date to be confirmed).
• Investigation into gentler conditioning for exa-cel is underway.
• The Institute for Clinical and Economic Review (ICER) determined that lovo-cel will be cost-effective if priced between $1.35M to $2.05M. ICER has made recommendations to encourage companies to set prices toward the lower end of this range to facilitate access and affordability across all insurance systems (in the USA).

Sources: https://investors.vrtx.com/news-releases/news-release-details/vertex-reports-second-quarter-2023-financial-results 
https://icer.org/news-insights/press-releases/icer-publishes-final-evidence-report-on-gene-therapies-for-sickle-cell-disease/

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 8 December 2023.

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 35 patients with SCD who had received exa-cel at the time of the analysis, 17 patients were evaluable for the primary and key secondary endpoint at the time of the data cut.
• 16/17 (94.1%) were VOC-free for at least 12 consecutive months
• Mean duration of VOC-free was 18.7 months, with a maximum of 36.5 months.
• 17/17 (100%) did not need hospitalisation for VOCs for at least 12 consecutive months
• All patients who received exa-cel, mean fetal hemoglobin was more than 30% of total hemoglobin by Month 3 and was then maintained at approximately 40.0% through follow-up, with pancellular distribution.

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