Obecabatagene autoleucel

The US Food and Drug Administration (FDA) has approved Autolus Therapeutics’ Aucatzyl (obecabtagene autoleucel) to treat acute lymphoblastic leukaemia (ALL). The CD19-directed CAR-T cell therapy has been specifically authorised for use in adults with relapsed or refractory B-cell precursor ALL. Aucatzyl is now the first CAR-T therapy approved by the US regulator with no requirement for a risk evaluation mitigation strategy programme, which is used for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Approximately 8,400 adults are diagnosed every year in the US and EU with ALL, an aggressive type of blood cancer that can also involve the lymph nodes, spleen, liver, central nervous system and other organs. Survival rates remain very poor for adults in the relapsed/refractory setting, with a median overall survival of eight months. Aucatzyl is designed to “overcome the limitations” in clinical activity and safety compared to current CD19 CAR T-cell therapies, according to Autolus. The FDA’s decision on the therapy was supported by positive data from the phase 2 FELIX trial, which enrolled B-cell precursor ALL patients who had relapsed following a remission lasting 12 months or less, had relapsed or refractory ALL following two or more prior lines of systemic therapy, or disease that was relapsed or refractory three or more months after allogeneic stem cell transplantation. Results showed that 42% of patients achieved the major efficacy outcome of complete remission within three months of Aucatzyl infusion, with a median duration of remission of 14.1 months. FELIX lead investigator, Elias Jabbour, University of Texas MD Anderson Cancer Center, said: “Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes. “This milestone approval, based on the demonstrated clinical benefit of Aucatzyl, brings new hope for adult patients with relapsed/refractory B-ALL.” Marketing authorisation applications for Aucatzyl in adult relapsed/refractory ALL are being reviewed by regulators in both the EU and UK.

Autolus’ Aucatzyl is a B-lymphocyte antigen CD19 CAR-T cell therapy. Credit: NDAB Creativity via Shutterstock. Autolus Therapeutics has secured US Food and Drug Administration (FDA) approval for Aucatzyl (obecaktagene autoleucel), its chimeric antigen receptor (CAR)-T cell therapy for adult patients with relapsed or refractory B cell precursor acute lymphoblastic leukaemia (B-ALL). The approval follows a heightened regulatory focus on CAR-T cell therapy safety this year. In April, the FDA mandated boxed warnings for these therapies due to rare cases of T cell malignancies. Aucatzyl’s labelling includes these standard warnings for risks associated with cytokine release syndrome (CRS) and neurologic toxicities. The FDA’s approval decision was based on data from the FELIX trial (NCT04404660), which evaluated the therapy in adult patients with relapsed or refractory B-ALL. In a subgroup of 65 patients with morphological disease and over 5% bone marrow blasts, Aucatzyl demonstrated a 63% overall complete remission (CR). The main efficacy outcome — CR within three months — was achieved in 42% of patients, with a median duration of remission of 14.1 months. Aucatzyl showed a relatively low incidence of severe adverse events in the FELIX trial, with only 3% of patients experiencing Grade 3 CRS and 7% reporting Grade 2 or 3 immune effector cell-associated neurotoxicity syndrome (ICANS). There were no Grade 4 or 5 CRS events. Despite the risks, the FDA did not require a risk evaluation and mitigation strategy (REMS) programme for Aucatzyl, a decision in line with recent regulatory changes aimed at easing CAR-T therapy monitoring requirements. In June, the FDA removed a requirement for clinicians to report serious cases of the two most common side effects as part of its REMS programme for Gilead’s treatments Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel). REMS programmes are typically implemented after drug approval when the FDA determines that a medication needs to be closely monitored. With this approval, Aucatzyl enters a market that includes Gilead’s Tecartus, which gained FDA approval for B-ALL in 2021. Autolus has not yet disclosed the list price for Aucatzyl, which is also under review for market authorisation in the UK and European Union, with submissions to the European Medicines Agency (EMA) and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) accepted in 2024. Production for Aucatzyl will take place at Autolus’s manufacturing facility in Stevenage, UK. In the announcement accompanying the approval, Dr. Elias Jabbour, US lead investigator of the FELIX study and professor of leukaemia, ALL Section Chief, at The University of Texas MD Anderson Cancer Center, Houston, Texas said: “Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Optimise your cell therapy process: a guide to cell thawing Typically carried out at the point of care, errors in cell therapy thawing could compromise treatment efficacy, leading to significant patient impact as well as high costs and a compromised reputation for the product’s developer. This guide addresses how cell thawing has historically developed into the new techniques used today, along with the physical and biological implications of key metrics and components such as warming rate and ice structure. Also included are reviews of key studies from scientific literature and a consideration of the interactions between cooling and warming rates, as applicable to cell and gene therapies. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Cytiva Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy