Patients with relapsed/refractory multiple myeloma now have two chimeric antigen receptor T (CAR-T) therapy options available in the fifth line of therapy (5L). Last month, the US Food and Drug Administration (FDA) approved Johnson & Johnson’s and Legend Biotech’s Carvykti (cilta-cel), following the approval of Bristol-Myers Squibb’s Abecma (ide-cel) last March. Both agents are BCMA antigen-targeting autologous modified CAR-T cells. While competition between the two drugs is expected to be fierce, commercial success is guaranteed for both due to physician excitement and the fact that they address a high level of unmet need.

Carvykti’s FDA approval was based on results from the Phase II CARTITUDE-1 single-arm trial, which evaluated 97 eligible patients who had received at least three prior lines of therapy. At the time of data cut-off, the overall response rate was 97.9%, with 78.4% of patients achieving a stringent complete response. The median duration of response was 21.8 months. Typical side effects for CAR-T cells include cytokine release syndrome (CRS) and neurotoxicity. Carvykti led to 95% of patients experiencing CRS, but only 5% of these were Grade III or higher. Regarding neurotoxicity, the most common adverse event (AE) was encephalopathy at 30%, of which 6% was Grade III or higher. While cross-trial comparisons should not inform regulatory decisions, Carvykti’s efficacy data compared favourably to the data from the Phase II KarMMa pivotal trial of Abecma, while in terms of AEs, Abecma and Carvykti had very similar outcomes.

While high clinical uptake is expected in the 5L for both agents, a move into the earlier lines of therapy can lead to very high revenues in multiple myeloma and rapidly change the competitive dynamics. Both drugs have ongoing clinical trials in the fourth, third and second lines of therapy. Abecma has, however, another advantage in its ongoing Phase I/II trial for newly diagnosed patients, with readouts expected as early as 2025. GlobalData does not anticipate a first-line approval without a large Phase III randomised trial, pushing the therapy’s clinical use well beyond 2025.

Abecma’s current first-mover advantage is anticipated to translate to much higher sales than Carvykti is forecast to see in the absence of a head-to-head comparison. In addition, Abecma has already been approved in the EU and Japan, and it achieved $164m in sales during its first year of launch. Carvykti’s approval in other markets is still pending. Another deciding factor for physicians will be the successful manufacturing rate for either CAR-T agent, as that issue has plagued similar drugs in other indications. GlobalData’s patient-based forecasts estimate that both agents will become blockbusters, but note that Abecma will likely gain the upper hand with $1.9bn in peak sales, compared to $1.2bn for Carvykti.

Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.

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