A New Zealand-developed CAR-T therapy is entering the registration phase. The ENABLE-2 trial, led by the Malaghan Institute, is a single-arm Phase 2 clinical trial evaluating atlacabtagene autoleucel (Atla-cel, WZTL-002) in 60 adult patients with relapsed or refractory large B-cell lymphoma. The trial, which began in July 2024, is recruiting patients in Wellington, Auckland, and Christchurch to generate efficacy and safety data to support registration in New Zealand and Australia. The study design, which compares Atla-cel to existing CD19 CAR-T clinical data rather than using a randomized control group, means that the magnitude of the complete response rate, as well as the consistency of the patient population and follow-up period, will be key to demonstrating the therapy's potential for approval.

Atla-cel is a third-generation CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy that uses the patient's own T cells. It is being developed under the code WZTL-002, without a separate brand name. It features an anti-CD19 binding moiety derived from FMC63, a CD28 costimulatory domain, and a Toll-like receptor 2 (TLR2) signaling domain, as well as CD3zeta. Wellington Zhaotai Therapies is the developer, with BioOra responsible for manufacturing and commercialization, and the Malaghan Institute sponsoring the clinical trial. The key value proposition of this design is to maintain anti-tumor activity while reducing cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), thereby broadening access to treatment.

The ENABLE-1 Phase 1 clinical trial demonstrated a complete response rate of 52% at 3 months in 30 treated patients, with no severe CRS or ICANS. ENABLE-2 aims to confirm that these signals are maintained in a larger patient population and in patients who have failed prior lines of therapy, with complete response and neurotoxicity as key endpoints. The automated local manufacturing process can reduce transportation and waiting times compared to existing supply chains that ship cells to overseas manufacturing facilities, which could be a clinical advantage in island healthcare systems. However, as a single-arm trial, the durability of response and overall survival will be as important as the initial response rate.

The therapy will compete with Yescarta (axicabtagene ciloleucel) from Gilead Sciences (GILD), Breyanzi (lisocabtagene maraleucel) from Bristol Myers Squibb (BMY), and Kymriah (tisagenlecleucel) from Novartis (NVS), all of which are CD19-targeted autologous CAR-T therapies. The FDA approved Yescarta on October 18, 2017, Kymriah for the indication of adult relapsed or refractory large B-cell lymphoma on May 1, 2018, and Breyanzi on February 5, 2021. Epkinly (epcoritamab, CD20×CD3) and Glofitamab (CD20×CD3), both bispecific antibodies, are also competing standard treatments that offer convenient administration. Yescarta's 2025 pre-approval revenue is estimated at USD 1.495 billion, demonstrating the commercial potential of CD19 CAR-T therapies. However, Atla-cel, as a pre-approval Phase 2 asset, must demonstrate clear advantages in safety, manufacturing cost, and time to treatment.