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-141 (phase 3 clinical trial for children ages 2 – 11 with TDT):
• 15 patients have been dosed with CASGEVY
• 5/15 (33.3%) had β0/β0 or β0/β0 -like genotypes
• All 15 TDT pts required ≤2 mobilization cycles
• All (8/8) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin (Hb) of at least 9 g/dL.
• Longest duration of transfusion independence was 28.5 months.
• One patient died from multi-organ failure due to severe veno-occlusive disease related to the busulfan conditioning.
• 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

2. CLIMB-111 (phase 1/2/3 clinical trial for TDT patients aged 12 – 35) or CLIMB131 (long term follow up):
• 56 patients received CASGEVY and had a median follow-up of 4.4 years (maximum follow-up 6.9 years)
• 45/56 patients had severe genotypes (β0/β0 or β0/β0-like)
• 98.2% (55/56) patients achieved transfusion independence with a median transfusion-free duration of 4 years
• Mean total Hb was maintained at normal/near normal levels of ≥12 g/dL and mean HbF was ≥11 g/dL from Month 6 onward. Allelic editing in bone marrow and blood remains stable over time.
• There were no deaths or malignancies.

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

• Approximately 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-141 (phase 3 clinical trial for children ages 2 – 11 with TDT):

• • 13 patients have been dosed with CASGEVY
  • 5/13 (38.5%) had β0/β0 or β0/β0 -like genotypes
  • All 13 TDT pts required ≤2 mobilization cycles
  • All (6/6) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin (Hb) of at least 9 g/dL.
  • Following CASGEVY infusion, 12/13 are transfusion-free, with the longest duration of transfusion-free just under two years (range 2.3–22.5 months).
  • One patient died from pneumonia in the setting of multi-organ failure due to severe veno-occlusive disease related to the busulfan conditioning.
  • 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-111 (phase 1/2/3 clinical trial for TDT patients aged 12 – 35) or CLIMB-131 (long-term follow-up):

• 2% (55/56) of patients achieved transfusion independence with a mean duration of 41.4 months (range 13 – 72.3 months).
• Mean total Hb was maintained at normal/near normal levels of ≥12 g/dL, and mean HbF was ≥11 g/dL from Month 5 onward. Allelic editing in bone marrow and blood remains stable over time.
• There were 7 cases (7/56; 12.5%) of hepatic veno-occlusive disease; none resulted in end-organ dysfunction, all were related to busulfan, and all resolved after defibrotide treatment. There were no deaths or malignancies.

3. 6/7 patients achieved adequate stem cell collections in one cycle (1 required a repeat cycle) in real-world experience from Manchester (UK). In 2/7 the final gene-edited cell doses exceeded the minimum target threshold.

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
Correction of ineffective erythropoiesis and durable clinical benefit with exagamglogene autotemcel for transfusion-dependent β-thalassemia
Real-world experience with apheresis for gene therapy in transfusion-dependent βthalassemia: The largest single-center report

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)

Sources: 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 continue to be explored.

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

• • A total of 56 patients had received exa-cel by the cut-off date of August 2024 (CLIMB-111 and CLIMB-131), 35 with severe genotypes [β⁰/β⁰or β⁰/β⁰-like].
  • Of the 54 patients evaluable,
    • 53 (98.1%) achieved transfusion independence.
    • For all patients, mean total Hb ≥12g/dL Month 5 onward and mean HbF was ≥ 11g/dL Month 5 onward
  • Serum ferritin and LIC decreased steadily and did not increase over time.
  • Follow up extends more than 6 years for TDT patients.

Sources: Vertex Reports First Quarter 2025 Financial Results | Vertex Pharmaceuticals
DURABLE CLINICAL BENEFITS AND IMPROVEMENT OF TISSUE IRON OVERLOAD… – Locatelli F – EHA-3620 – Jun 13 2025
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

• > 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 66^th 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 29^th 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)
  • 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 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 65^th 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