FDA Approves Manufacturing Change, Shortening Wait Time for Axi-cel


The axicabtagene ciloleucel manufacturing process has received FDA approval for a change to reduce the median turnaround time.

  • The new process reduces the median turnaround time from 16 to 14 days.

  • With this manufacturing change, patients can receive their axicabtagene ciloleucel (axi-cel; Yescarta) treatment sooner, which may improve their outcomes.

  • The news follows a recent FDA decision to allow additional overall survival data from ZUMA-7 (NCT03391466) to be added to the label of axi-cel.

The FDA has approved a manufacturing process change resulting in a shorter manufacturing time for axi-cel, resulting in an anticipated reduced turnaround time (TAT) from 16 days to 14 days.1

The median TAT is measured from the moment a patient's T cells are collected, also known as leukapheresis, to when the final product is ready for infusion. The manufacturing process, which customizes the patient's cells for a single-use cell therapy, is a crucial step within this timeframe.

“For patients with relapsed or refractory large B-cell lymphoma [LBCL], every day matters as the patient’s disease can be aggressive and worsen rapidly,” said Cindy Perettie, executive vice president, Kite, a Gilead Company, in a press release. “[Axi-cel] is the first and only treatment to demonstrate superior overall survival over the standard-of-care as a second-line treatment with curative intent for these patients, and today’s decision by the FDA allows us to further shorten our delivery time of [axi-cel] so that patients have the best possible chance of survival.”

This manufacturing process change comes as Kite prepares for a significant launch of axi-cel as a second-line treatment for LBCL. The news follows a recent FDA decision to allow additional patient survival data to be added to the label of the chimeric antigen receptor (CAR) T-cell therapy.2

The positive patient survival data shows that treatment with axi-cel significantly improved outcomes, reducing the risk of death by 27.4% compared with standard-of-care, a relative 38% improvement in overall survival (OS), in the pivotal phase 3 ZUMA-7 trial.

CAR T-cell attack cancer cell and healthy cells © LASZLO - stock.adobe.com

CAR T-cell attack cancer cell and healthy cells © LASZLO - stock.adobe.com

The ZUMA-7 study is an international, phase 3 trial which randomly assigned patients with large B-cell lymphoma who had relapsed within a year of first-line chemoimmunotherapy into 2 equal groups.3 The first group received axi-cel while the other received chemotherapy followed by stem cell transplant if they responded. The primary end point of the study was event-free survival according to a blinded central review, and key secondary end points were response and OS. Investigators also assessed safety.

With an overall estimated median follow-up of 46.7 months, the primary OS analysis led to a statistically significant improvement with axi-cel vs in the standard therapy arm, even with 57% in the standard-of-care arm subsequently receiving cell therapy off protocol.2 At 39 months, the OS rates were 55.9% with axi-cel and 46% with standard-of-care.

“Given that each cell therapy batch is unique to each patient, manufacturing is central to how we deliver our therapies, and quality, reliability, and speed are critical,” said Chris McDonald, strategic value partners, global head of technical operations, Kite, in a press release.1 “As the global leader in cell therapy, patients and physicians count on our 96% manufacturing success rate, and with a reduced manufacturing time in the United States, we will continue to expand the reach of Yescarta to even more patients.”

About Axi-cel

Axi-cel is a CD19-directed genetically modified autologous T-cell immunotherapy used to treat a variety of patients and cancer types, including LBCL and follicular lymphoma (FL). Specifically, these indications include adults with LBCL refractory to first-line chemoimmunotherapy or those who have relapsed within 12 months, adults with relapsed or refractory LBCL after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal LBCL, high-grade B-cell lymphoma, DLBCL arising from FL, and adults with relapsed or refractory FL following treatment with 2 or more lines of systemic therapy.

The FL indication is approved under accelerated approval due to its response rate. However, continued approval depends on a confirmatory trial proving its clinical benefit. Additionally, axi-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

“Since the first CAR T cell therapies were approved more than 5 years ago and the volume of patients treated has grown from hundreds to several thousand patients each year, we have significantly strengthened our knowledge and understanding of cell therapy delivery,” added David Miklos, MD, PhD, a Kite clinical investigator/chief of blood and marrow transplant and cell therapy at Stanford University, in a press release. “Time is a critical factor in cell therapy, and it can make the difference between a patient being able to receive CAR T or their cancer progressing to the point where they are no longer strong enough for treatment. Therefore, optimizing steps in the process and ultimately reducing the time to CAR T-cell therapy infusion is paramount.”

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, a Gilead Company. January 30, 2024. Accessed January 30, 2024. http://tinyurl.com/2dtktncz
2. U.S. FDA approves label update for Kite’s Yescarta® CAR T-cell therapy to include overall survival data. News release. Kite, a Gilead Company. December 21, 2023. Accessed January 30, 2024. http://tinyurl.com/5h8hkt4h
3. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

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