Unanimous support from FDA for new R/R Multiple Myeloma indication for earlier use of Janssen’s Carvykti

The Oncologic Drugs Advisory Committee (ODAC) unanimously supported supplemental biologics license application (sBLA) 125746/74 for Carvykti (ciltacabtagene autoleucel [cilta-cel]), submitted by Janssen Biotech, Inc (Janssen), for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide [Revlimid from Bristol-Myers Squibb Company].

The proposed indication is to reduce the number of treatments patients need to receive to be eligible for cilta-cel therapy. Despite the number of early deaths in the cilta-cel study arm, the committee agreed that the benefits of treatment with this agent outweigh the risks, largely due to the potential for patients to be free of any treatment for potentially long periods of time after receiving cilta-cel.

In support of the sBLA, the sponsor submitted results from CARTITUDE-4, which met its primary endpoint and demonstrated a statistically significant improvement in progression-free survival (PFS) in participants who received cilta-cel compared to those who received standard therapy. The FDA asked the panel if these findings were sufficient to support a positive risk-benefit assessment of cilta-cel for the proposed indication. The ODAC acknowledged the agency’s concerns about the higher rate of early deaths in the cilta-cel arm. Panelists agreed that the early deaths were concerning, but it is unclear what caused the deaths and whether they were related to the product. The subjects will need to be followed over the long term, panelists stated. Several committee members attributed their support for cilta-cel to the overwhelming response to treatment in terms of PFS and overall survival (OS), emphasizing the potential for longer survival for many patients.

Proposed Indication
Carvykti (ciltacabtagene autoleucel) for the treatment of adult patients with RRMM who have received ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.

Proposed Dose
Cilta-cel 0.5‑1.0 × 106 CAR-positive viable T cells per kg of body weight as a single-dose infusion with a maximum dose of 1 × 108 CAR-positive viable T cells per single-dose infusion.