December 18, 2019

Impact: Moderate

  • Gilead’s Kite subsidiary has announced that it has submitted a BLA for the investigational CAR-T KTE-X19 for the treatment of patients with relapsed or refractory mantle cell lymphoma (R/R MCL).
  • The BLA is based on data from the Phase 2 ZUMA-2 trial which demonstrated an ORR of 93% (CR rate = 67%) in 60 evaluable patients. Enrolled patients had MCL that was refractory to or had relapsed following up to 5 prior lines of therapy.
  • Grade 3 or higher cytokine release syndrome (CRS) and neurotoxicity were seen in 15% and 31% of patients, respectively. No Grade 5 CRS or neurological events were observed.
  • Detailed findings from ZUMA-2 were presented Monday at ASH 2019.
  • KTE-X19 has been granted FDA Breakthrough Therapy and EMA PRIME status for the MCL indication.
  • Kite anticipates submitting a European Marketing Authorization Application in early 2020.

inThought Analysis

KTE-X19 has demonstrated impressive activity in mantle cell lymphoma and an MCL approval would be an important step for Gilead as it continues to make the case that autologous CAR-Ts can be sustainable commercial products. According to ZUMA-2 ASH presenter Michael Wang (MD Anderson), “These are the highest response rates to date in patients with prior BTK inhibitor failure.” The median time to response was 1 month (range=0.8-3.1 months) and the mDoR had yet to be reached. The 12 month OS was 83%.

An approval would make Gilead the first company to have two approved CAR-Ts on the market. Further, the potential for additional sales would help justify Gilead’s $11.9B acquisition of Kite in 2017. In 2018, Yesacrta (axicabtagene ciloleucel) sales for R/R large B-cell lymphoma were only $264M. Over the past four quarters, sales were $415M. This is an improvement, but still far from blockbuster levels.

Mantle cell lymphoma is an aggressive B cell NHL subtype that is considered incurable. Standard therapy involves induction chemotherapy and allogeneic stem cell transplant for fit patients and a variety of less intense Rituxan-based regimens for less fit patients. Regardless of upfront therapy, relapses are seen as inevitable and agents such as Revlimid and the BTK inhibitors Imbruvica, Calquence, and the recently approved Brukinsa are used in this setting. KTE-X19 would be a welcome therapeutic option for multiply relapsed patients.

KTE-X19 is identical to Yescarta but is produced with an additional purification step designed to remove any remaining tumor cells. It will be interesting to see how Gilead elects to price KTE-X19 if it is approved for MCL given general hand wringing about the high cost of CAR-T products.

Source: Gliead Press Release