Data from pivotal studies of CASGEVY in children ages 5‑11 years with severe sickle cell disease or transfusion‑dependent beta thalassemia demonstrate the therapy’s transformative potential in younger patients.
Efficacy and safety data in children 5‑11 are consistent with the durable benefit‑risk profile established in patients 12 years and older.
Vertex plans to begin global regulatory submissions for CASGEVY in children 5‑11 in the first half of 2026.
BOSTON – Vertex Pharmaceuticals (Nasdaq: VRTX) presented new data on CASGEVY® (exagamglogene autotemcel) for patients five years and older living with severe sickle cell disease (SCD) or transfusion‑dependent beta thalassemia (TDT). The results, including the first clinical data from pivotal studies in children ages 5‑11, will be discussed at the American Society of Hematology (ASH) Annual Meeting.
CASGEVY is already approved for eligible patients 12 years and older in the United States, Great Britain, the European Union, Saudi Arabia, Bahrain, Kuwait, Qatar, Canada, Switzerland and the United Arab Emirates.
“These results— the first clinical data ever presented on a genetic therapy for children 5‑11 with SCD—again demonstrate the transformative potential of CASGEVY,” said Dr. Carmen Bozic, Executive Vice President, Global Medicines Development and Medical Affairs at Vertex. “With dosing completed in the 5‑11 age group and the FDA’s National Priority Voucher in hand, we will initiate global filings in early 2026 to bring this therapy to eligible children as quickly as possible.”
Dr. Haydar Frangoul, Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute, added, “Having seen the dramatic impact of CASGEVY in older patients, I am eager to offer this option to younger patients before the most severe disease complications develop.”
First presentation of data in children ages 5‑11 treated with CASGEVY
- Sickle cell disease: In the Phase 3 CLIMB‑151 study, 11 children received CASGEVY. All four patients with ≥12 months of follow‑up achieved the primary endpoint of being free from vaso‑occlusive crises for at least 12 consecutive months (VF12). No patient experienced a VOC after infusion, with the longest VOC‑free interval approaching two years (range 3.2–24.1 months).
- Transfusion‑dependent beta thalassemia: In the Phase 3 CLIMB‑141 study, 13 children were treated. Six patients with ≥12 months of follow‑up achieved transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin ≥9 g/dL (TI12). Twelve of the 13 remain transfusion‑free, with the longest period just under two years (range 2.3–22.5 months). One patient died from pneumonia and multi‑organ failure related to busulfan conditioning.
- Safety in the younger cohort mirrors the profile observed in older patients, reflecting myeloablative conditioning and autologous stem‑cell transplant risks.
- Consistent durability of fetal hemoglobin (HbF) elevation and stable allelic editing were observed across age groups.
Longer‑term data for patients 12 years and older
Updated data from the pivotal studies show sustained benefits. In SCD, 100% of patients (45/45) achieved VF12 across the CLIMB‑121 and long‑term CLIMB‑131 studies, with a mean VOC‑free duration of 35.3 months (range 12.9–67.7 months). In TDT, 98.2% (55/56) reached TI12, with a mean transfusion‑independence duration of 41.4 months (range 13–72.3 months). The safety profile remains consistent with myeloablative conditioning and autologous transplant.
Market and Business Implications
The data bolster CASGEVY’s position as the first disease‑modifying, one‑time therapy for both SCD and TDT, addressing two high‑cost, high‑burden indications. In the United States, the median life expectancy for SCD patients is ~45 years, with lifetime healthcare costs estimated at $4‑$6 million. For TDT, median survival is ~37 years and lifetime costs range from $5‑$5.7 million. Successful expansion into the pediatric market could substantially increase Vertex’s addressable market, potentially adding several hundred million dollars in annual revenue once the therapy is priced in line with existing gene‑editing products.
From a technology standpoint, CASGEVY leverages non‑viral, ex vivo CRISPR/Cas9 editing of the erythroid‑specific enhancer of the BCL11A gene, reactivating fetal hemoglobin production. This precise double‑strand break offers a favorable risk profile compared with viral vectors, reducing insertional mutagenesis concerns while delivering durable HbF expression. Manufacturing scalability—currently a bottleneck for autologous cell therapies—will be critical. Vertex’s partnership network and its experience with cystic fibrosis gene therapies position it well to streamline the supply chain, but the 6‑month production window per patient remains a logistical challenge for broader adoption.
Regulatory momentum is strong. The FDA’s National Priority Voucher grants Vertex an accelerated 1‑2‑month review clock for the supplemental Biologics License Application (sBLA) targeting the 5‑11 age group. If approved, the therapy could become the first CRISPR‑based product to receive a priority review for a pediatric indication, setting a precedent that may influence future gene‑editing approvals.
About Sickle Cell Disease (SCD)
SCD is an inherited hemoglobin disorder characterized by sickled red blood cells that obstruct microvasculature, causing painful vaso‑occlusive crises (VOCs), organ damage and reduced life expectancy. Recurrent VOCs drive substantial healthcare utilization, with hospitalization rates averaging 3‑4 admissions per year in severe cases.
About Transfusion‑Dependent Beta Thalassemia (TDT)
TDT requires lifelong regular blood transfusions and iron chelation therapy. Complications include organomegaly, bone deformities, and cardiac iron overload, contributing to a high burden of care and reduced lifespan.
About CASGEVY® (exagamglogene autotemcel)
CASGEVY is a one‑time, ex vivo CRISPR‑edited autologous hematopoietic stem‑cell therapy. By disrupting the BCL11A erythroid enhancer, the treatment re‑activates fetal hemoglobin (HbF) synthesis, alleviating the pathophysiology of both SCD and TDT.
Clinical Development Program (CLIMB Studies)
The CLIMB program consists of Phase 1/2/3 trials (CLIMB‑111, CLIMB‑121, CLIMB‑141, CLIMB‑151) evaluating a single dose of CASGEVY in patients 12‑35 years and children 2‑11 years. Dosing for the 5‑11 cohort is complete, and Vertex plans to expand enrollment to ages 2‑4. All participants are invited to enroll in the long‑term CLIMB‑131 study, which follows patients for up to 15 years post‑infusion.
Regulatory Roadmap
Vertex intends to submit a supplemental Biologics License Application in the United States during the first half of 2026, leveraging the FDA’s National Priority Voucher. The accelerated review pathway is expected to reduce time to market, positioning CASGEVY as a first‑in‑class therapy for pediatric SCD and TDT.
Safety Information (U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION)
CASGEVY is indicated for patients 12 years and older with SCD who experience frequent VOCs, and for patients with β‑thalassemia who require regular transfusions. The therapy involves a myeloablative conditioning regimen followed by infusion of the edited autologous stem cells. Patients experience transient cytopenias (low platelets and white blood cells) until engraftment occurs. Monitoring for infection, bleeding, and other complications is essential.
Patients must avoid blood, organ, tissue, or cell donation for life after treatment. The most common adverse events are thrombocytopenia and neutropenia, requiring close clinical observation.
About Vertex
Vertex Pharmaceuticals is a global biotechnology firm focused on innovative medicines for serious diseases. The company’s pipeline includes therapies for cystic fibrosis, sickle cell disease, beta thalassemia, neuropathic pain, kidney disease, type 1 diabetes, and myotonic dystrophy. Vertex maintains research and commercial operations across North America, Europe, Australia, Latin America and the Middle East.
Forward‑Looking Statements
This release contains forward‑looking statements regarding the clinical benefits of CASGEVY, regulatory plans, and market expectations. Actual results may differ due to risks and uncertainties, including clinical trial outcomes, regulatory approvals, and manufacturing challenges. Vertex does not assume any obligation to update these statements.
(VRTX‑GEN)
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