Winship study drives FDA approval for new leukemia therapy

The U.S. Food and Drug Administration (FDA) has approved obecabtagene autoleucel (Aucatzyl, Autolus Inc.) for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), a fast-growing blood cancer that starts in the bone marrow and affects the body’s ability to fight infection. The approval follows results of a landmark study published in The New England Journal of Medicine and co-authored by Winship Cancer Institute of Emory University researcher and hematologist-oncologist Martha Arellano, MD. According to the FDA, this approval was based on findings from the pivotal phase 2 FELIX trial, which demonstrated a complete remission rate of 42% within three months of infusion and a median duration of remission of 14.1 months.

The study demonstrated significant improvements in remission rates for patients with limited treatment options, positioning obecabtagene autoleucel as a new standard of care for this challenging cancer. Key findings include an overall remission rate of 77% and a complete remission rate of 55%, with a median event-free survival of 11.9 months and a median overall survival of 15.6 months. These results highlight the therapy's potential to significantly extend and improve patient outcomes.

“This FDA approval underscores the importance of collaborative research and its impact on patient outcomes,” says Arellano, who served as the local principal investigator on the trial at Winship Cancer Institute and is a member of Winship’s Discovery and Developmental Therapeutics Research Program, professor of hematology and medical oncology at Emory University School of Medicine, program director of the Emory Hematology and Medical Oncology Fellowship Program and a specialist in treating leukemia and myelodysplastic syndromes. “We are proud to have played a role in advancing this transformative therapy.”

Obecabtagene autoleucel is a CD19-directed genetically modified autologous T cell immunotherapy which works by genetically modifying the patient’s own T cells to target and destroy cancer cells. Unlike previous CAR T-cell therapies, this treatment uses a novel intermediate-affinity design to reduce severe immune-related toxic effects, such as cytokine release syndrome, a systemic inflammatory response, and neurotoxicity, which can cause confusion, seizures or other nervous system issues if severe (grade 3). These effects, in grade 3 or higher, occurred in only 2.4% and 7.1% of patients, respectively. This design represents a refinement of CAR T-cell therapy, aiming to maintain effectiveness while improving safety and tolerability, especially for adult patients who are more susceptible to severe side effects.

The therapy offers a much-needed option for adults with ALL who have not responded to other treatments. Obecabtagene autoleucel involves collecting a patient’s T cells, genetically modifying them to express a chimeric antigen receptor (CAR) targeting the CD19 antigen and reinfusing them to attack and eliminate malignant B cells. This approach provides a critical new treatment pathway for patients with relapsed or refractory B-cell ALL, a group that previously had limited effective therapies, according to the FDA.

The research was funded by Autolus Therapeutics.