Adult Acute Lymphoblastic Leukemia
Adult B-ALL (acute lymphoblastic leukemia) is an aggressive type of leukemia characterised by the presence of too many B lymphocytes in the bone marrow and peripheral blood. Without treatment adult ALL usually progresses very rapidly. Prognosis for patients based on current treatments is very poor.
Combination chemotherapy enables 90% of adult patients to enter complete remission, but only 30-40% of these patients will achieve long term remission. The median overall survival is < 1 year in r/r adult ALL.
The only redirected T cell therapies for adult patients are blinatumomab and brexucabtagene autoleucel. These therapies are highly active, but achieving long term remissions remains challenging. Patients are generally more fragile with co-morbidities, yet CAR T toxicities in this setting have been notable with high incidences of severe CRS and cases of fatal neurotoxicity.
A significant unmet need remains for adult ALL patients. A successful therapy requires high level of activity and sustained persistence paired with good tolerability.
Adult ALL is a significant unmet medical need
Median OS <1 year
Obe-cel in adult ALL
The Phase 2 pivotal FELIX study of obe-cell in adult ALL met its primary endpoint at an interim analysis with an overall response rate (ORR) of 70%. Additional data were presented at ASCO and EHA in June 2023, with longer term follow up data and subgroup analysis data expected at ASH in late 2023, as well as at medical conferences in H1 2024. A BLA submission to the US FDA is planned by the end of 2023. In this indication, obe-cel has been granted orphan drug designation by the FDA, PRIME designation by EMA and ILAP designation by the MHRA.
Data from the FELIX Phase 1b and ALLCAR19 Phase 1 studies in relapsed / refractory adult ALL patients shows a high levels of complete responses across both studies in the absence of high grade (≥Grade 3) cytokine release syndrome (CRS) and with low rates of immune effector cell-associated neurotoxicity syndrome (ICANS).
In the ALLCAR19 study where longer term follow up data is available, we continue to observe sustained responses with obe-cel without the requirement for subsequent therapy. The event free survival, a measure of long term efficacy, is 46% at 24 months, with some patients approaching up to 42 months of durability. These data support the curative potential of obe-cel as a standalone therapy in r/r adult ALL patients.