Obe-cel, an investigational therapy utilizing CD19 CAR T cells, aims to address the limitations observed in the clinical effectiveness and safety of existing CD19 CAR T cell treatments. By incorporating a rapid target binding off-rate, obe-cel is specifically designed to minimize excessive activation of the modified T cells, potentially reducing toxicity and decreasing the likelihood of T cell exhaustion. These features have the potential to enhance the longevity of the modified T cells and improve their ability to repeatedly target and eliminate cancer cells. Obe-cel is currently undergoing development to address numerous medical conditions, with the most advanced and strategically significant focus being on adult Acute Lymphoblastic Leukemia.
Data from adult R/R B-Acute Lymphoblastic Leukemia patients treated with obe-cel in the pivotal FELIX study a Phase Ib/II trial (NCT04404660) were presented in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The primary endpoint of the study was the overall response rate, and the secondary endpoints included the duration of response, MRD negative CR rate, and safety.
In the pivotal morphological cohort of the FELIX trial, a total of 112 patients diagnosed with R/R B-Acute Lymphoblastic Leukemia were enrolled, out of which 94 patients (84%) received treatment with obe-cel. Among the treated patients, 76% achieved an ORR [54.3%-complete response (CR) and 21.3% -incomplete hematological recovery (CRi)], while 97% of the respondents with assessable samples exhibited deep remission with no detectable minimal residual disease (MRD).
Furthermore, at a median follow-up of 9.5 months, 61% of the responders maintained ongoing remission without the need for new anti-cancer treatments. The kinetics of CAR T cells demonstrated outstanding engraftment and persistence, aligning with the findings of the previous ALLCAR19 study.
The safety analysis revealed a potentially superior tolerability profile, with only 3% (3 out of 94) of patients experiencing Grade ≥3 cytokine release syndrome (CRS), and 7% (7 out of 94) of patients experiencing immune effector cell-associated neurotoxicity syndrome (ICANS). The majority of the observed toxicity occurred in patients with a high disease burden. It is worth noting that out of the 7 cases of Grade ≥3 ICANS, 6 were observed in patients with an exceptionally high tumor burden of more than 75% bone marrow blasts during lymphodepletion. Overall, Grade ≥3 adverse events were reported in 79% of patients, with neutropenia (36.2%) and thrombocytopenia (25.5%) being the most commonly observed side effects.
“We are very encouraged by the outcome of the FELIX study. Obe-cel shows low immunotoxicity, high complete remission rates, and excellent CAR T expansion and persistence in adult B-Acute Lymphoblastic Leukemia. These data are consistent with the prior ALLCAR19 study and suggest that obe-cel has the potential for long-term clinical benefit in adult B-Acute Lymphoblastic Leukemia patients without additional therapies” –Expert Opinion.
Expected adverse events (AEs) with CAR T-cell therapies include CRS in up to 70% of patients and neurotoxicity in 30-50% of patients. These can have a big impact on how patients are treated and how long they stay in hospitals. Obe-cel data from FELIX Study demonstrates favorable response rates along with acceptable incidences of CRS and neurotoxicity. At present, TECARTUS (brexu-cel) is the sole CAR T-cell therapy approved for use in adult B-Acute Lymphoblastic Leukemia. In contrast to TECARTUS, obe-cel employs a unique, low-affinity binding approach, allowing for more natural interaction with its target.
With “Nucleus” as their commercial manufacturing facility, Autolus Therapeutics expects to file a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) by the end of 2023. Filings of EU and UK marketing authorization applications are planned for H1 2024. Obe-cel has been granted regenerative medicine advanced therapy (RMAT) designation by FDA in R/R B-Acute Lymphoblastic Leukemia, Prime designation by EMA in R/R B-Acute Lymphoblastic Leukemia, and Innovation Licensing and Access Pathway (ILAP) designation by the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) in Adult R/R B-Acute Lymphoblastic Leukemia. To summarize, although more data and a longer follow-up is needed, obe-cel appears to have less neurotoxicity and overall low rates of CRS, and patients are responding well.
Get a more detailed overview of the key developments in the domain at: Acute Lymphoblastic Leukemia (ALL) Market, Acute Lymphoblastic Leukemia Epidemiology Forecast, Acute Lymphoblastic Leukemia (ALL) Pipeline Insight, CAR T-Cell Therapy for Acute Lymphoblastic Leukemia (ALL) Market, CAR T-Cell Therapy for Acute Lymphoblastic Leukemia Pipeline Insight