Phase III Trial of Exagamglogene Autotemcel Meets Primary and Key Secondary Endpoints

The ongoing phase III CLIMB SCD-121 trial of exagamglogene autotemcel (exa-cel) in patients with sickle cell disease (SCD) reported that primary and key secondary endpoints had been met. The pre-specified interim analysis was presented at the 65th ASH Annual Meeting & Exposition.

The 24-month ongoing study is focusing on patients aged 12 to 35 years with SCD and a history of at least two vaso-occlusive crises (VOCs) per year in the two years before screening. The primary efficacy endpoint was the proportion of patients free of severe VOCs for at least 12 consecutive months. Key secondary endpoints included freedom from inpatient hospitalization for severe VOCs for at least 12 consecutive months (VF12) and freedom from severe VOCs for at least nine consecutive months. Patients were evaluated 60 days after the last red blood cell transfusion.

As of February 10, 2023, 42 patients with SCD (mean age, 21.2 years) received exa-cel. Following infusion, all patients experienced engraftment of neutrophils and platelets within a median of 27.0 and 34.5 days, respectively.

Nineteen out of the 20 patients evaluable for the primary endpoint were free of VOCs for at least 12 consecutive months (95% CI, 75.1-99.9; P<.0001), and 100% were free from hospitalizations for VOCs (95% CI, 83.2-100.0; P<.0001). Additionally, 96.7% of patients were VOC-free for at least nine consecutive months (95% CI, 82.8-99.9; P<.0001). The VOC-free duration in patients achieving VF12 was 21.8 months, with 18 patients remaining VOC-free through follow-up.

Hemoglobin levels were consistently maintained at 11.0 g/dL or higher, with a significant increase in fetal hemoglobin observed. The proportion of edited BCL11A alleles remained stable over time. Quality-of-life measures indicated clinically significant improvements from baseline.

All patients experienced at least one adverse event (AE), with the majority being grade 1 or 2. Forty patients (95.2%) reported grade 3/4 AEs. Common AEs included nausea (66.7%), stomatitis (61.9%), febrile neutropenia (52.4%), headache (52.4%), and vomiting (52.4%). Most AEs and serious AEs occurred within the first six months after infusion. There were no serious AEs considered related to exa-cel, and no study discontinuations or malignancies were reported.

Reference

Frangoul H, Locatelli F, Sharma A, et al. Exagamglogene autotemcel for severe sickle cell disease. Abstract #1052. Presented at the 65th American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, California.