FDA Expects Decision on Cilta-cel Approval by February 2022

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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The U.S. Food and Drug Administration (FDA) is expected to decide by the end of February whether or not to approve ciltacabtagene autoleucel, known as cilta-cel, an investigational CAR T-cell therapy for the treatment of relapsed or refractory multiple myeloma.

The FDA extended its expected decision date to allow sufficient time to review information about an updated analytical method — which the FDA had requested and was recently submitted by the investigational therapy’s co-developers Legend Biotech and Janssen.

The two companies met with the FDA earlier this month to discuss the application; no additional clinical data have been requested.

“We are working closely with Janssen and the FDA to facilitate an efficient and thorough review of the [application] for cilta-cel,” Ying Huang, PhD, CEO and chief financial officer at Legend, said in a press release.

Cilta-cel’s use involves the collection and genetic modification of a person’s own T-cells — immune cells with the ability to kill cancer cells — to make them better at fighting cancer.

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Specifically, the therapy comprises T-cells engineered to recognize and kill cells containing the B-cell maturation antigen (BCMA) — a protein found at high levels on the surface of myeloma cells — while leaving healthy cells unharmed. The modified cells are then expanded and infused back into the patient.

Legend and Janssen sought FDA approval of cilta-cel — previously called JNJ-4528 in the U.S. and Europe and LCAR-B38M in China — based on data from a Phase 1b/2 clinical trial called CARTITUDE-1 (NCT03548207).

That study, sponsored by Janssen, tested cilta-cel in people with relapsed or refractory multiple myeloma. These patients either had initially responded to prior treatment, but the cancer came back (relapsed), or did not respond to prior treatment at all (refractory).

Specifically, CARTITUDE-1 included patients who had received at least three prior lines of treatment, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and a CD38 inhibitor, or who failed to respond to treatment with a PI and an IMiD. Among the 97 participants in the study, the median number of prior therapies was six, and most were refractory to three classes of treatment.

Interim data from the trial showed high response rates after a median of 12.4 months, or just over one year. These early results showed that 97% of patients experienced a reduction in cancer burden, and 67% had no detectable cancer.

More recent data, with a median follow-up time of 18 months, showed a similarly high response rate (98%), with 80% of participants having no detectable cancer. That suggests a deepening of clinical response over time, according to the researchers.

At 18 months, two-thirds of patients also were alive and without signs of disease progression, the team noted.

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“The efficacy results observed in heavily pretreated patients with multiple myeloma receiving cilta-cel are remarkable,” Saad Z. Usmani, MD, of the Levine Cancer Institute, in North Carolina, and the study’s principal investigator, said in a release from Janssen earlier this year.

“With the possibility of achieving the progression-free survival reported and responses deepening as observed in the longer-term follow-up, I’m hopeful that cilta-cel will be part of the armamentarium in the future for patients in need of an additional treatment option,” Usmani said.

The most common adverse events, or side effects, reported in the CARTITUDE-1 trial were low levels of immune cells and other types of blood cells and platelets. Cytokine release syndrome — a potentially life-threatening complication of immunotherapies — occurred in 95% of patients given cilta-cel, though 99% of cases resolved within two weeks of onset.

“We remain confident that cilta-cel has shown great promise in patients with relapsed and refractory multiple myeloma, and we are focused on making this therapy available to them in the US as soon as possible,” Huang said.

In the U.S., cilta-cell has been granted the FDA’s breakthrough therapy and orphan drug designations, which are intended to promote the development of treatments with the potential to improve care for serious or rare diseases.