Autolus Therapeutics has received FDA approval for Aucatzyl (obecabtagene autoleucel, or obe-cel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This marks Autolus' first approved product and provides a new CAR T-cell therapy option for this aggressive blood cancer.
In B-cell ALL, the bone marrow produces an excess of abnormal B-lymphocytes. Aucatzyl is a CAR T-cell therapy that involves extracting a patient's T cells and engineering them to target CD19, a protein found on the surface of these abnormal B cells. While Gilead Sciences’ Tecartus also targets CD19 and is approved for ALL, Aucatzyl is designed with the goal of improved safety and efficacy through a mechanism called "serial killing."
Mechanism of Action and Clinical Data
Following CD19 recognition and binding, Aucatzyl releases cytotoxic proteins and then disengages from the cancer cell to target another, a process referred to as "serial killing." Aucatzyl is engineered for a faster "off-rate," meaning it disengages from each target cell more rapidly than other CAR T-cell therapies. This rapid disengagement is intended to minimize excessive T-cell activation, potentially reducing adverse effects and T-cell exhaustion, thereby improving the therapy's durability.
The FDA approval was based on data from an open-label, single-arm trial involving adults with CD19-positive B-cell ALL that had relapsed or was refractory to at least two prior lines of therapy. The primary endpoint was the rate and duration of complete remission. Among the 65 patients evaluable for efficacy, 27 (42%) achieved complete remission within three months. The median duration of response was 14.1 months.
Safety Profile
Aucatzyl carries a black box warning for cytokine release syndrome, neurotoxicity, and T cell malignancies, consistent with other CAR T-therapies. However, the rates of severe complications observed with Aucatzyl were notably low. Cytokine release syndrome was reported in 75% of patients, but only 3% experienced Grade 3 events, and no Grade 4 or 5 events occurred. Neurotoxicity was reported in 64% of patients, with Grade 3 or higher complications in just 12% of cases.
Market and Future Directions
William Blair analyst Matt Phipps noted that Aucatzyl's response rates are similar to Tecartus, but Aucatzyl distinguishes itself with a better safety profile. Notably, the FDA is not requiring a Risk Evaluation and Mitigation Strategy (REMS) for Aucatzyl, which is unique among approved CAR T-therapies and should reduce the burden on treatment centers. Autolus is also exploring the potential of Aucatzyl in autoimmune disorders driven by B-cell activity, with an ongoing Phase 1 study in systemic lupus erythematosus.
Autolus' manufacturing facility in Stevenage, United Kingdom, will produce Aucatzyl for global markets. Cardinal Health will serve as the distribution partner in the U.S. Aucatzyl will compete with Amgen’s Blincyto, a CD19-targeting monoclonal antibody with $861 million in 2023 sales, and Gilead’s Tecartus, which had $370 million in global sales in 2023. William Blair projects Aucatzyl could reach peak sales of approximately $300 million, with an estimated initial price of $450,000.
