Existing CAR-T therapies have been saved for blood cancer patients who’ve tried multiple treatments—until now.
With a first-in-class nod, the FDA has cleared Yescarta, a CD19-directed CAR-T therapy made by Gilead Sciences’ Kite Pharma, for treating patients with large B-cell lymphoma that is refractory to one prior therapy or that relpases within 12 months of first-line chemoimmunotherapy.
Friday’s approval puts Yescarta ahead of Bristol Myers Squibb’s rival drug Breyanzi, which expects an FDA decision for the same second-line lymphoma indication by June 24.
Kite Pharma CEO Christi Shaw has put the eligible U.S. patient population for Yescarta in the second-line setting at 14,000 compared with 8,000 patients for its original third-line use. The new indication could get Yescarta $1.5 billion in peak sales over time, according to analysts at RBC Capital Markets.
The optimism—and the FDA nod—came from the phase 3 Zuma-7 trial. The study showed Yescarta reduced the risk of disease progression, death or the need for a new therapy by 60.2% compared to standard of care, which involves chemotherapy and stem cell transplant. At two years, 40.5% of Yescarta takers were still alive and didn’t require additional cancer treatment or experience cancer progression, versus 16.3% for the control arm.
It’s also worth noting that, while 94% of patients in the Yescarta group successfully received the CAR-T therapy, only 36% of those in the control arm actually made it to stem cell transplant, Shaw noted during an interview.
Still, Shaw believes that Yescarta won’t see a sudden spike in demand, because changing 20-plus years of practice won’t be easy.
Most of the patients are in the community versus large treatment centers, and educating community physicians takes time, Shaw explained. Because large B-cell lymphoma isn’t a common cancer, there could be a large time gap between an education interaction and the physician treating a patient.
At least reimbursement doesn’t seem to be as much of a hurdle as it was during the early days of CAR-T therapy. Medicare, which covers about half of eligible patients, is fully covering cell therapy, Shaw noted. Kite is talking to commercial payers, but “based on the robustness of the data, we don’t expect huge hurdles,” she said.
To help with Kite’s reimbursement discussions, the strong clinical data had already won Yescarta a category 1 backing on National Comprehensive Cancer Network (NCCN) guidelines for treating second-line aggressive LBCL, ahead of the FDA decision. A category 1 recommendation means there’s uniform consensus based on high-level evidence.
Kite will likely face second-line competition from Bristol Myers’ CAR-T therapy Breyanzi, which pared down the event-free survival risk by 65.1% in its own phase 3 trial. Novartis’ CD19-targeted CAR-T therapy Kymriah previously surprisingly failed in second-line LBCL.
Kite already has a three-year head start with Yescarta against Breyanzi on the market. And Shaw believes Yescarta also holds an edge when it comes to CAR-T cell therapies’ complex manufacturing process.
Yescarta has shown a median time of 16 days from drawing blood from a patient to final product release in the real world, whereas Breyanzi currently targets a 24-day turnaround.
Kite has also invested heavily in manufacturing to ensure a steady supply and to keep the turnaround time down. The company got an approval for an Amsterdam site during the pandemic, and it expects a Maryland facility to win clearance and start producing commercially mid-year. Plus, a third site in Oceanside, California recently begun producing engineered viral vectors for the cell therapy alongside an external contractor, Shaw said.
By comparison, BMS hit a manufacturing bottleneck for its multiple myeloma CAR-T therapy Abecma and it’s also working on improving vector supply for Breyanzi.