According to findings presented at the 2021 ASH Annual Meeting, the gene therapy bb111 demonstrated clinically meaningful improvements in quality of life (QOL) for adult patients with sickle cell disease (SCD), with improvements sustained up to 24 months after infusion.
The present analysis updates findings from the ongoing phase 1/2 HGB-206 study, which demonstrated complete resolution of severe vaso-occlusive events (VOEs), near-normalization of key hemolysis markers, and normalization of total hemoglobin with bb111 in certain participants.
The trial enrolled patients (older than 12 years, but younger than 50 years) with severe SCD and recurrent severe VOEs. Participants underwent plerixafor mobilization and apheresis followed by myeloablative busulfan conditioning and bb1111 infusion. In addition to laboratory and clinical assessments, patients were monitored for patient-reported outcomes (PROs) at baseline and every six months post-infusion through month 24.
PRO data at 24 months were available for 25 patients who received bb1111 (median age = 25 years; 40% female). The researchers explained that, for each PRO domain, patients from the overall population were stratified into two subgroups depending on whether their baseline score was “better or near” or “worse” than the population norm, to account for potential differences over time in QOL changes relative to baseline status.
Overall, the researchers found that patients with baseline scores “worse” than the population norm reported improvements in all domains at month six that continued up to month 24. Of note, mean pain interference decreased from 64.2 to 44.5. Pain intensity decreased from 6.5 to 1.8 from baseline to month 24, while fatigue decreased from 64.6 to 46.9 from baseline to month 18.
In addition, in patients with baseline scores “better or near” population norm, scores generally remained stable through two-year follow-up. For example, mean pain interference scores were 46.4 and 45.9 at the respective time points, while pain intensity scores were 2.0 and 2.8.
“When considering mean differences, values for patients overall showed meaningful change in all domains and the [pain intensity scales], with the exception of [anxiety outcomes],” the investigators reported.
The authors concluded that the improvements in PRO domains for patients with “worse” baseline scores were established early post-infusion and were sustained up to two years after infusion, while PROs did not worsen in SCD patients with near-normal baseline QOL measures. “These data show bb1111 for SCD not only improved hematologic parameters and resulted in complete resolution of severe VOEs, as presented elsewhere, but also provide sustained and clinically meaningful QOL benefit for patients,” they wrote. “Continued follow-up and analysis of patient-reported outcomes is needed to evaluate the long-term impact of bb1111 for SCD.”