Reducing Turnaround Time of Axi-Cel CAR T-Cells

Chris McDonald

Caption: Kite Pharma

The FDA has approved Kite Pharma’s manufacturing process change for axicabtagene ciloleucel (axi-cel; Yescarta). The new change is expected to reduce median turnaround time from leukapheresis to product release from 16 days to 14 days.¹

Time to treatment is an important factor in improving outcomes for patients receiving CAR T-cell therapy. Axi-cel was approved for the second-line treatment of LBCL in April 2022, for adult patients with disease refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy.²

CGTLive® spoke with Chris McDonald, Kite Pharma’s senior vice president and global head of technical operations, to learn more about the new manufacturing protocol. Although he was not able to share the specific changes made or in which domains the changes were made, he stressed that Kite has shown comparability between the 2 axi-cel products to the FDA with a comparability protocol. He acknowledged the unique role of manufacturing within the autologous cell therapy field in which it can be a differentiator and provide an edge to companies.

CGTLive: How does manufacturing play a unique role in the autologous cell therapy field?

Chris McDonald: It's an unusual industry - autologous cell therapy where your manufacturing can actually be a differentiator for you, and is a differentiator for Kite. I think we're the industry leaders in success rate, turnaround times, etc. So, I think it's unique... I've been in the pharma bio industry for 35 years, and this is definitely an interesting twist, how manufacturing can become a competitive advantage.

Why is this manufacturing approval important to the cell therapy treatment field?

McDonald: Kite has the industry's best turnaround time at 16 days, with a very high success rate, which is also, we believe, an industry best at 96%. And turnaround time - we understand the importance for patients. The patients that are being treated are all very sick and often, even though we're potentially the best in the industry at doing it, we have patients actually canceling their orders because their health deteriorates before they're treated. And so everyday really matters for these patients. So, while we are the best from where we're at, we're still focused on improving. The latest improvement reduces our manufacturing time from approximately 7 days, and it does vary based on patient cells, but approximately 7 days tend to down to approximately 5 days, reducing it by 2 days. And then ultimately, our overall turnaround time, which includes the logistics, from the hospital to our manufacturing time, the quality testing, and release, we expect to go from 16 days to 14 days. So, it is an important improvement for patients.

What can you share with CGTLive about the changes made?

McDonald: The improvements we made are not public knowledge. Because manufacturing is a competitive advantage, a lot of times we're a bit guarded with our secret sauce, I would say. What I can tell you is that we were able to reduce the manufacturing time but still demonstrate comparability to the existing product. That's a key point. So, we developed a comparability strategy where we were able to show the 2 manufacturing processes produced a comparable product. We gained agreement with FDA on a comparability protocol, then to complete the improvement, we executed that comparability protocol at both of our commercial manufacturing sites that are producing for the United States market, and that was in El Segundo, California and our Frederick, Maryland facility.

Transcript has been edited for clarity.

REFERENCES

1. Kite Receives U.S. FDA Approval of Manufacturing Process Change Resulting in Reduced Median Turnaround Time for Yescarta® CAR T-cell Therapy. News release. Kite Pharma. January 30, 2024.https://www.gilead.com/news-and-press/press-room/press-releases/2024/1/kite-receives-us-fda-approval-of-manufacturing-process-change-resulting-in-reduced-median-turnaround-time-for-yescarta-car-tcell-therapy
2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma