A relatively novel class of drugs called bispecific T-cell engagers (BiTEs) present a serious threat to the market position of Bristol Myers-Squibb’s Abecma (ide-cel) for the treatment of relapsed or refractory multiple myeloma (RRMM) as they leverage clinical advantages such as improved duration of response to therapy and quicker administration, says GlobalData, a leading data and analytics company.

Research by GlobalData’s pharma team explains that patients with RRMM have poor clinical outcomes due to therapeutic options that do not control the disease effectively in the long term. Abecma is currently marketed for RRMM patients in the fifth line, but recent data has highlighted that there is still much left to be desired for treating these patients.

Sam Warburton, Oncology Analyst at GlobalData, comments: “BiTEs have garnered high industry interest for their ability to redirect T-cells to engage with and kill tumor cells. They are one of the main competitors to adoptive cell therapy for treating RRMM. Abecma was putatively believed to mark a sea change in the way RRMM patients are treated in later lines of therapy by being the first approved BCMA-targeted cell therapy, however, patient outcomes are still highly suboptimal.”

Real-world data presented at the American Society of Hematology* earlier this month showed that the majority (69%, n=56) of patients eligible to receive Abecma suffered disease relapse while waiting for apheresis—a procedure that must be performed before administration of Abecma. The cumulative incidence of death at 12 months while waiting for CAR-T was 31.9%, and 27% of patients remain waiting for CAR-T therapy at 12 months. Moreover, Abecma appears to have inferior duration of response to BiTEs, specifically Janssen’s Tecvayli (teclistamab), which recently gained FDA approval in October 2022. The below chart highlights key clinical data comparing the currently marketed cell therapies against BiTEs that are either marketed or in pre-registration.

Warburton continues: “BiTEs offer comparable safety and efficacy profiles to Abecma, however, Janssen’s Carvykti comes out on top for clinical outcomes with an impressive ORR of 97%. Importantly, BiTEs have a serious advantage, considering that they can offer comparable clinical efficacy without requiring the patient to wait several weeks to receive therapy—unlike CAR-T therapy which requires a long and complex manufacturing process. As the data at ASH has shown, treatment delays can lead to disease relapse and death in significant proportions of patients. Altogether, BiTEs present a more clinically attractive option and are likely to outcompete cell therapy, especially Abecma, in 2023 when the second BiTE, talquetamab, is likely to be approved by the FDA.”

GlobalData estimates that talquetamab will be approved in late 2023 and will likely be a blockbuster agent, thereby cementing Janssen’s market-leading position in the RRMM space. It may also outcompete BMS’ Abecma on grounds of superior practicality.

Warburton adds: “Tecvayli, being conveniently subcutaneously administered, is likely to be the standard of care for RRMM patients in the fifth line. However, the intravenously administered talquetamab presents a novel mechanism of action which is independent of BCMA and, therefore, can be used in patients that are refractory to BCMA-targeted agents. Janssen is set to enjoy a period of BiTE market dominance by virtue of a first-to-market advantage, however, competition is soon on the horizon, with several novel agents in mid-late phase clinical trials.

*Samer Al Hadidi et al, ‘3588 Clinical Outcome of Patients with Relapsed Refractory Multiple Myeloma Listed for BCMA Directed Commercial CAR T Therapy’, presented at the American Society of Hematology on Sunday Dec 11 2022