Gilead's Kite wins FDA nod for new CAR-T manufacturing process to speed up Yescarta turnaround

Ever since the first CAR-T launches several years ago, lengthy manufacturing timelines have been one drawback of this promising drug class. But with a new FDA blessing, Gilead Sciences is expediting production of its Yescarta and shortening the therapy's overall turnaround time.

The FDA has approved a new manufacturing process change for Yescarta, Gilead’s Kite Pharma unit said Tuesday. The approval allows the company to shorten the CAR-T cell manufacturing time for Yescarta from an average of seven days to five days, Chris McDonald, Kite’s head of technical operations, told Fierce Pharma.

Thanks to this shortened production timeline, Kite will be able to reduce the median turnaround time for Yescarta—beginning with collection of a patient’s T cells and ending with final product release—from 16 days to 14 days, the company said.

“For patients with relapsed or refractory large B-cell lymphoma, every day matters as the patient’s disease can be aggressive and worsen rapidly,” Cindy Perettie, the newly minted head of the Gilead cell therapy business, said in a statement.

The manufacturing upgrade comes as Kite works through an important launch for Yescarta as a second-line therapy for large B-cell lymphoma. Last month, the FDA allowed additional patient survival data to be added to Yescarta’s label, which now shows that the CD19 CAR-T slashed the risk of death by 27.4% compared with standard of care in the phase 3 ZUMA-7 trial.

In a competitive market, Yescarta has held an edge over Bristol Myers Squibb's rival drug, Breyanzi, when it comes to product delivery efficiency. While Yescarta now boasts a median turnaround time of 14 days, BMS has been targeting 24 days for Breyanzi.

Because of the wait time, some patients’ cancer may progress while their individualized therapies are being manufactured. In ZUMA-7, eight of the 178 patients who underwent cell collection didn’t receive Yescarta. In Breyanzi’s Transform trial in the second-line setting, three of the 92 patients randomized to the Breyanzi arm didn’t get the BMS CAR-T medicine.

Feedback from doctors also suggests Gilead’s Kite is a more reliable CAR-T maker than BMS, both in terms of slot availability and successful delivery. And as Kite aims to maintain its industry-leading manufacturing success rate, the new optimized manufacturing process could help with capacity, McDonald said.

“If you think about a patient’s cells being in the plant two less days, it’s actually freeing up capacity for other patients,” McDonald said.

“I don’t think we would make this change if it impacted our success rates,” McDonald added. “We expect that [for] that 96% success rate, we’ll be able to maintain that.”

Being reliable also means having a predictable turnaround timeline. After all, a shortened median turnaround time, if coupled with a wider range, wouldn’t be helpful for planning purposes.

By targeting a median turnaround of 14 days, Kite means it will be able to accomplish the majority of cases by that time, McDonald said.

Further, Yescarta’s turnaround schedule fits with how often cancer patients typically sees their oncologists, Perettie said.

Kite’s turnaround time commitment allows doctors “to very reliably schedule that hospital bed and not be concerned that they’re going to schedule it, the patient’s going to show up, and the cells don’t,” Perettie said in the same interview. 

Currently, Kite produces commercial CAR-T therapies from two U.S. facilities in El Segundo, California, and Frederick, Maryland, and it has a European plant in Amsterdam. In addition, the company also self-supplies viral vectors from a plant in Oceanside, California.

If needed, Kite would be able to expand its capacity by up to four times based on its existing infrastructure, McDonald said.

Manufacturing capacity isn’t what’s limiting Yescarta these days. Instead, making the cell therapy available to more patients through increased referrals from community doctors and new community-based treatment centers is a top priority.

To help address shortfalls in access, Kite is helping community practices work with large hospitals to build out CAR-T-related services, Perettie said.

All of this comes as the FDA demands a classwide boxed warning outlining the safety risk of secondary T-cell malignancies for all existing CAR-T therapies. Kite has not observed a causal relationship between its CAR-T therapies and secondary T-cell malignancies after about 17,700 patients treated worldwide, Perettie said.

Besides the manufacturing efforts, Kite is running the phase 3 ZUMA-23 comparing Yescarta with standard of care as first-line treatment in patients with high-risk large B-cell lymphoma. These are patients who’ve quickly progressed after only one cycle of a Rituxan-and-chemo-based regimen. As Perettie noted, these patients don’t respond to chemo and have no other options available.