Exagamglogene Autotemcel Demonstrates Improved Health-related QOL in Patients with Severe SCD

The ongoing phase III CLIMB SCD-121 study presented an interim analysis of health-related quality of life outcomes in patients with severe sickle cell disease (SCD) who received exagamglogene autotemcel (exa-cel) during the 65th ASH Annual Meeting & Exposition.

Seventeen patients with severe SCD (defined as ≥2 vaso-occlusive crises per year in the two years prior to screening) aged 12 to 35 years were included in the analysis. Patients received a single dose of exa-cel, a non-viral, ex vivo CRISPR/Cas9 gene-edited autologous cell therapy.

Patient-reported outcomes were evaluated as a secondary endpoint in the trial from baseline through 24 months. Health-related quality of life was assessed via the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), the 11-point pain Numerical Rating Scale (NRS), and EuroQol Quality of Life Scale 5 dimensions five levels of severity (EQ-5D-5L). The EQ-5D-5L included a descriptive system in addition to visual analog scale (VAS), Functional Assessment of Cancer Therapy (FACT) Bone Marrow Transplant (BMT), and bone marrow transplant subscale.

“Substantial and clinically meaningful improvements exceeding minimal clinically important difference (MCID) thresholds were observed in all assessed patient-reported outcomes measures,” the authors reported.

EQ-5D-5L health utility and EQ VAS substantially improved by month six through month 24. FACT-General total scores also improved from baseline through month 24, and patients demonstrated improvements in subscale categories of physical, social/family, emotional, and functional well-being.

The ASCQ-Me subscales of emotional (standard deviation [SD], 17.7), social (SD, 23.8), stiffness (SD, 7.9), and sleep impact (SD, 8.4), as well as BMT scores also demonstrated clinically meaningful improvements from baseline through month 24. The ASCQ-Me pain-related subscales—which assess pain impact, pain episode frequency, and pain severity—showed the most substantial numerical improvement in pain episode frequency.

Lastly, pain NRS measurements improved by month 12 and were sustained through month 24 (SD, ‒1.8).

According to the investigators, “These results demonstrate the broad clinical benefits of exa-cel in patients with SCD.”

Reference

Sharma A, Frangoul H, Mapara M, et al. Improvements in health-related quality of life after exagamglogene autotemcel in patients with severe sickle cell disease. Abstract #4999. Presented at the 65th American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, California.