- Patients with an aggressive type of lymphoma did significantly better after receiving Gilead's cancer cell therapy Yescarta than those who were given a standard combination of high-dose chemotherapy and stem cell transplant in a major clinical trial, a finding that could support broader use of the company's CAR-T treatment.
- Results from the trial, called ZUMA-7, showed Yescarta cut the risk of disease worsening, death or progression to a new lymphoma treatment by 60% versus standard of care. Data on overall survival favored Yescarta, but patients have not been followed for long enough to make a statistical comparison, Gilead said in a Monday statement on the study findings.
- The rate of side effects to treatment were "consistent with or lower" than Yescarta's known safety profile, according to Gilead. Six percent of patients experienced severe cytokine release syndrome and 21% experienced severe neurotoxicity, two side effects that are often associated with CAR-T treatment.
Gilead's results closely follow an announcement from Bristol Myers Squibb that its rival cell therapy Breyanzi succeeded in a similar clinical trial. Both study outcomes represent major proof points for CAR-T drugs, as they could help expand use of the complex treatments — currently only approved after patients essentially run out of other options — into earlier lines of care.
Gilead did not disclose detailed data from the study beyond the headline finding on the study's primary goal, a clinical trial endpoint known as event-free survival. Full results will be presented at a future medical conference, the company said.
But Gilead does plan to start discussions with the Food and Drug Administration, as well as regulators in Europe and elsewhere, about applying later this year for an expanded approval of Yescarta.
Approved in October 2017, Yescarta was the first CAR-T drug cleared for use in diffuse large B-cell lymphoma, the most common type of non-Hodgkin lymphoma. Gilead, which had acquired Yescarta's original developer Kite Pharma a few months earlier, started the Phase 3 study comparing Yescarta to chemotherapy and stem cell transplant soon after.
The trial is larger, and has run longer, than Bristol Myers' TRANSFORM study, which also compared Breyanzi to chemotherapy and stem cell transplant in previously treated lymphoma patients. The results Monday reflect a median follow-up time of two years, Gilead said.
Overall, 359 patients were enrolled into ZUMA-7 through 77 centers spread across the U.S., Canada, Europe, Israel and Australia. They'd either relapsed or their cancers became resistant to first-line chemotherapy. Nearly a third of study participants were over 65 years of age, with a range from 22 to 81 years old.
In addition to the significant improvement on event-free survival reported for Yescarta, more patients responded to the CAR-T drug than standard treatment.
"The outcomes for patients relapsing after frontline chemotherapy in this study are dramatically improved with rapid referral (to a CAR T center) and a single infusion of [Yescarta] as compared to chemotherapy and consolidative autologous transplant, the longstanding second-line standard of care," said Frederick Locke, the lead ZUMA-7 investigator and an oncologist at the Moffitt Cancer Center, in a statement provided by Gilead.
Time to treatment is particularly critical for CAR-T, which involves a complicated and logistically challenging process of extracting patient immune cells for genetic engineering and subsequent reinfusion. Making Yescarta generally takes Gilead a little more than two weeks from start to finish.
Should Yescarta win approval for earlier use in lymphoma care, RBC Capital Markets analyst Brian Abrahams expects those administration challenges will keep CAR-T limited to mostly academic centers already familiar with the process.
Still, an approval could significantly increase sales of Yescarta, which costs $373,000 for the one-time infusion. Gilead reported $160 million in revenue from the drug in the first three months of 2021, an increase of $20 million from the same period one year ago.
While Yescarta is the leading CAR-T treatment for lymphoma, Bristol Myers aims to challenge Gilead, as do a number of biotechs working to develop "off-the-shelf" cell therapies for the blood cancer.