Autolus Therapeutics is nearing a critical milestone with its autologous CAR-T cell therapy, obe-cel, indicated for relapsed/refractory (r/r) adult B-cell Acute Lymphoblastic Leukemia (B-ALL). The Food and Drug Administration (FDA) is set to announce its decision on the Biologics License Application (BLA) by the Prescription Drug User Fee Act (PDUFA) date of November 16, 2024. This decision could mark a significant advancement in the treatment of this aggressive hematological malignancy.
Obe-cel's Clinical Profile
The BLA submission is supported by data from the Phase 1b/2 FELIX study. In this study, obe-cel demonstrated a 78% overall response rate (ORR), defined as complete remission (CR) or complete remission with incomplete hematological recovery (CRi), among all patients who received the therapy (99/127 patients). According to Autolus, at a median follow up of 21.45 months, 40% of responding patients were in ongoing remission without subsequent stem cell transplant (SCT) or other therapy. The median event-free survival (EFS) was 11.9 months, and the median overall survival (OS) was 23.8 months. The estimated 12-month EFS and OS rates were 49.5% and 61.1%, respectively.
These results compare favorably to existing CAR-T therapies. For instance, Tecartus, another CD19-targeting CAR-T cell therapy, achieved a 65% complete remission rate in its ZUMA-3 study with a median follow-up of 12 months. Four-year data from the ZUMA-3 study showed a median OS of 25.6 months and a four-year OS rate of 40% (95% CI, 28-52).
Safety and Tolerability
Beyond efficacy, safety is a critical consideration for CAR-T cell therapies. Data from the FELIX study suggest that obe-cel may offer a more favorable safety profile compared to some existing therapies. Only 3% of patients experienced grade 3 or higher cytokine release syndrome (CRS), and 7% experienced grade 3 or higher Immune effector cell-associated neurotoxicity syndrome (ICANS). In contrast, a retrospective study of real-world outcomes with Tecartus reported 6% of patients experiencing grade 3 or higher CRS and 39% experiencing grade 3 or higher ICANS.
Market Opportunity and Competitive Landscape
If approved, obe-cel would enter a market with existing CAR-T therapies like Tecartus and other treatments such as Blincyto (blinatumomab), a bispecific antibody. Autolus estimates the addressable market for obe-cel to be approximately 3,000 patients annually, representing a market opportunity of around $1.5 billion. The company anticipates peak revenues for obe-cel to be in the region of $300 million.
Financial Position and Partnerships
Autolus appears well-positioned for the potential commercial launch of obe-cel, with a reported cash position of over $700 million as of the end of Q2. Additionally, the company has established partnerships with BioNTech, Moderna, and Bristol Myers Squibb, which could provide further financial and strategic support.
Expansion Opportunities
Beyond B-ALL, Autolus is exploring the potential of obe-cel in other indications, including autoimmune diseases like systemic lupus erythematosus (SLE). Data from an ongoing study in SLE patients are expected before the end of the year. The company's pipeline also includes other CAR-T cell therapy candidates in earlier stages of development.
