B-cell lymphoblastic leukemia accounts for 80–85% of total ALL cases. Although this percentage can differ depending on age at diagnosis, race, or ethnicity. As per DelveInsight, there were ~5,500 cases of B-cell ALL in the US in 2023.

Obecabtagene autoleucel (obe-cel, AUTO1) is an autologous CAR-T cell therapy that incorporates a fast off-rate CD19 binder. This design aims to enhance the safety profile of the treatment while also improving the expansion and persistence of the CAR-T cells within the patient's body. The fast off-rate characteristic allows the CAR-T cells to disengage more quickly from the CD19 antigen after binding, reducing the risk of excessive immune activation and associated toxicities. This approach not only aims to provide a more manageable safety profile but also enhances the durability of the therapeutic response by promoting sustained CAR-T cell activity and longevity in patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL).

Further, the half-life of the target interaction of obe-cel is 9.8 s compared with 21 min with tisagenlecleucel. CD19 negative relapse is a major cause of treatment failure after CD19 CAR T-cell therapy for pediatric B-ALL. To address this, Autolus has designed AUTO1/22 to target both CD19 and CD22 using the fast-off rate CD19 CAR from obe-cel combined with a novel CD22 CAR capable of effective signaling in response to low antigen density.

Get more insights of the report @ B-Cell Chronic Lymphocytic Leukemia Market

In the FELIX study, 20.5% of patients had undergone three lines of therapy, and 15% had received four or more lines, with a median of two prior therapies ranging from 1 to 6. Approximately 44% patients had received prior allo-SCT in the total cohort.

As of data cut-off date, i.e., February 7, 2024, 40% of responders were in ongoing remission without allo-SCT at median 21.5 months follow up. Total 127 patients were infused with obe-cel and 78% (n =99) have shown complete response at a median followup of 21.5 months.

This study showed that ongoing CAR T persistence at 6 months is associated with improved EFS. In Patients who had ongoing persistence the 12-month EFS rate was 87.3%, where in those who lost persistence it was 59.3%.

KOL insights

“There are potential differences that obe-cel can offer that may push forward how CAR T-cell therapy can help patients. The unique mechanism of action and favorable safety profile of obecabtagene autoleucel could improve outcomes in patients with B-cell acute lymphoblastic leukemia (B-ALL) and pave the way for future advances with CAR T-cell therapy in this population” – MD, United States.

“With obe-cel, investigators tried to develop a low-affinity CD19 binder that would allow the CAR T cells to bind and then release rapidly; the hope was this would do two things: the first was that it would decrease (some of) the toxicity associated with CAR T-cell therapy, specifically cytokine release syndrome (CRS) and neurologic adverse effects (AEs). The second is that it would improve the health of the T cell and limit T-cell exhaustion so the T cells can stay active for a longer period.”– Associate member, Moffit Cancer Center, the US

Also, Read @ T-Cell Receptor Therapy Market Size

Conclusion 

The 12-month EFS and OS rates stand at 49.5% and 61.1%, respectively, suggesting a possibility of long-term stability. SCT consolidation post obe-cel did not enhance EFS or OS outcomes. Persistence of CART cells correlates with improved EFS. These findings collectively support considering obe-cel as a standard treatment approach for adult patients with R/R B-ALL.

The approval and availability of Gilead's TECARTUS (brexucabtagene autoleucel), an autologous CD19-directed CAR T-cell therapy for relapsed or refractory B-ALL, brings into question the relative advantages of obe-cel. Although no direct comparative clinical trials exist between these two therapies, available data suggest they have similar efficacy outcomes. However, obe-cel, designed with an accelerated target binding off-rate to reduce excessive activation of the programmed T cells, may offer benefits in terms of decreased toxicity and a lower risk of T cell exhaustion. This design feature could make obe-cel a potentially safer and more durable option for patients.

Investigators hope obe-cel will provide an additional CD19-directed CAR-T cell option to their arsenal. Obe-cel’s unique mechanism of action mimics physiological T-cell receptor interactions. The agent has a lower affinity for CD19 than similar CAR-T products. This design helps avoid CAR-T cell over-activation and exhaustion.

In ALL, the competitive landscape of CAR-T cell therapies is less crowded, and there is a possibility to grab a huge market share by the pharma giants who are investigating CAR-T candidates for the treatment of ALL. The market for CAR-T cell therapies will ultimately grow over time. Despite the clinical success, CAR‐T cell therapies still face many challenges in clinical practice. Due to their complex nature, CAR‐T cell therapies are only offered at institutions capable of providing the equipment, resources, and clinical expertise needed to administer the therapy successfully. Furthermore, CAR‐T cell therapy costs can be as high. Therefore, the combination of limited offering centers and excessively high costs may prevent most patients from receiving this therapy. To develop the CAR-T-cell therapy there are two methods, i.e., allogeneic and autologous. However, more research is required to have an improved understanding of the possible benefits and disadvantages of each approach.