Ciltacabtagene Autoleucel FDA Approved it for Second-line Treatment of Multiple Myeloma
Ciltacabtagene Autoleucel FDA Approved it for Second-line Treatment of Multiple Myeloma
On April 5th, 2024 local time, Johnson & Johnson announced that the U.S. FDA has expanded the label for Johnson & Johnson and Legend Biotech’s multiple myeloma CAR-T therapy, making it an earlier treatment option for patients.
The FDA approved Ciltacabtagene Autoleucel (Carvykti) for the treatment of patients with multiple myeloma who have received at least one prior therapy. This cell therapy was initially approved in 2022 as a fifth-line treatment option, only applicable to patients who had exhausted multiple treatment options. Last year, Ciltacabtagene Autoleucel had global sales of $500 million, and with the expanded indication, sales of the drug are expected to reach $950 million this year.
According to Johnson & Johnson, there are approximately 21,000 eligible multiple myeloma patients in the fourth-line and later treatment settings, and 118,000 patients in the second and third-line treatment settings. The expanded label applies to patients who have previously received proteasome inhibitor and immunomodulatory agent therapies and are refractory to lenalidomide.
Despite the label expansion meaning that the patient population eligible for Ciltacabtagene Autoleucel is now larger, Legend Biotech CEO Ying Huang stated that the company expects most patients receiving the drug this year will still come from later lines of treatment. Additionally, Huang emphasized the drug’s potential in the second-line setting, noting that these patients may have received fewer immunosuppressive multiple myeloma treatments.
Huang said, “In later-line patients, the quality or quantity of the immune cells collected during the apheresis process may not be as good as for patients who have only received one line of treatment. This is why we think there is a strong scientific rationale for us to shift our focus to the second-line setting rather than the third, fourth, or fifth-line and beyond.”
The day before, the FDA also approved an expanded label for Bristol Myers Squibb and 2seventy bio’s competing multiple myeloma CAR-T therapy Abecma, making it available as a third-line treatment for certain patients. In 2021, Abecma became the first approved BCMA-targeted CAR-T therapy.
In March, FDA advisers unanimously voted to support the use of Ciltacabtagene Autoleucel in earlier treatment lines, despite the FDA’s concern about higher mortality rates in the first few months of the clinical trial for patients receiving Ciltacabtagene Autoleucel compared to those receiving standard therapy. The experts agreed that the long-term survival benefit outweighed the risks. In the pivotal CARTITUDE-4 trial, patients receiving Ciltacabtagene Autoleucel had higher mortality rates for about the first 11 months of the study, after which mortality rates were lower. Compared to standard therapy, Ciltacabtagene Autoleucel reduced the risk of disease progression or death by 59%.
The expanded labels for both Ciltacabtagene Autoleucel and Abecma include warnings and precautions regarding the early mortality observed in their respective clinical trials.
Legend Biotech and Johnson & Johnson stated that supply constraints have slowed the adoption rate, and the two companies have been working to increase manufacturing capacity in the U.S. and Europe, including expanding their agreement with Novartis last week to produce commercial Ciltacabtagene Autoleucel through 2029.
European regulators recommended Ciltacabtagene Autoleucel in February as a second-line or later option for multiple myeloma patients, with approval expected by late April. In December, the FDA added a black box warning to the Ciltacabtagene Autoleucel label regarding the risk of myelodysplastic syndrome and acute myeloid leukemia after treatment while investigating the risk of secondary malignancies across the CAR-T class. In January, the FDA required all CAR-T drugmakers to add black box warnings about different types of secondary malignancies in T-cell malignancies, although FDA officials and experts stressed that the benefits of these cancer therapies still far outweigh the safety risks.
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