Regulatory Decision Summary for Carvykti

The purpose of this supplemental new drug submission (SNDS) was to obtain authorization of Carvykti (Ciltacabtagene autoleucel) for the treatment of adult patients with multiple myeloma, who have received 1 to 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.

Market authorization was based on the results of the phase 3, randomized, open-label, multicenter study (MMY3002) that compared Carvykti to Daratumumab, Pomalidomide, Dexamethasone (DPd) or Pomalidomide, Bortezomib, Dexamethasone (PVd) in adults with lenalidomide-refractory multiple myeloma after 1-3 prior lines of therapy including a proteosome inhibitor, and an immunomodulatory drug.

The study enrolled 419 participants who were randomized 1:1 to receive PVd or DPd, or Carvykti. At the pre-planned interim analysis, the study demonstrated a statistically significant improvement in progression-free-survival (PFS) in the Carvykti arm compared to the PDd/DPd control arm. The clinical benefit was also supported by significant improvements in complete response rate and overall response rate. Overall survival data was immature at the time of the primary analysis.

The safety profile of Carvykti in MMY3002 remained consistent with the known safety profile for Carvykti. The most common adverse reactions (in ≥ 20% patients) in the Carvykti arm were pyrexia, cytokine release syndrome (CRS), hypogammaglobulinemia, musculoskeletal pain, fatigue, diarrhea, upper respiratory tract infection, headache, and viral infection. Deaths due to a TEAE were reported in 10 (4.8%) patients in the Carvykti arm, including COVID-19 pneumonia, pneumonia, neutropenic sepsis , and respiratory failure versus 5 patients in the PVd/DPd arm.

Secondary primary malignancies were reported with Carvykti including hematological malignancies (myelodysplastic syndrome, acute myeloid leukemia, and CAR-positive T-cell lymphoma).

Risk Management Plan (RMP) for Carvykti was reviewed by Health Canada and considered acceptable.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

The Canadian Product Monograph has been adequately updated for key safety and efficacy findings associated with Carvykti.

Overall, based on the evidence reviewed, the benefit of Carvykti outweighs the potential risks for the treatment of adult patients with multiple myeloma, who have received 1 to 3 prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, and who are refractory to lenalidomide.

The recommended dose of Carvykti is 0.5-1.0x10⁶ CAR-positive T cells per kilogram of body weight, consistent with the currently authorized dose.

A Notice of Compliance was recommended.

For further details about Carvykti, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.