Large pharmaceutical companies producing personalized blood cancer treatments are striving to halve the manufacturing turnaround time in the coming years to deliver these therapies sooner in a patient's disease course.
CAR-T therapies, used for the sickest patients who have failed standard treatments, involve removing a patient's T cells—a crucial component of the immune system—and re-engineering them to recognize and attack malignant cells before reinfusion.
Companies like Gilead Sciences, Novartis, Johnson & Johnson, and Bristol Myers Squibb have generated billions from these treatments, which can extend the lives of patients with aggressive, advanced cancers by months or years.
Reducing the time between T cell removal and reinfusion could benefit patients who might otherwise become too sick during the process, according to three physicians, the companies, and analysts.
The prices for these one-time treatments range from $400,000 to nearly $600,000, with profit margins estimated at around 50%. Expanding the patient population is therefore significant.
Oppenheimer & Co analyst Hartaj Singh noted that currently, only about 1 in 5 eligible patients receive CAR-T treatments. "It's complex manufacturing using the patient's own cells, but because some of the responses are so long and durable, physicians will opt for it," Singh said. "It's the biggest gun out there."
When Novartis launched the first CAR-T therapy in 2017, the time to treatment was as long as 37 days. At Gilead, it is now down to 14 days. Further improvements in automation and regulatory adjustments could reduce this time even more.
Singh mentioned that physicians suggested a one-week turnaround could increase treatment uptake to 2 or 3 out of 5 eligible patients.
Quicker manufacturing times could be a competitive advantage, especially when therapies are approved for the same cancer or population and directly compete, giving companies an edge over more rapidly available treatments such as antibodies or antibody-drug conjugates.
To manufacture the treatments, a patient's T cells are isolated, frozen, and shipped to manufacturers. The cells are then purified, modified, expanded, undergo quality control, and are re-frozen and shipped back for infusion.
Gilead is testing new technology that may cut two days from the process by using healthier and more potent younger cells. The company is also looking to fully automate parts of manufacturing that are currently semi-automated and to gain regulatory approval to shorten quality control time.
Novartis aims for 10 days or less in the U.S. for its next generation of treatments through its rapid manufacturing platform T-Charge. Its treatment, Kymriah, currently takes 3 to 4 weeks with a target of 22 days. T-Charge allows for the engineered cells to multiply within the patient, reducing the need for extended cell expansion before infusion.
Dr. Chijioke Nze of MD Anderson Cancer Center stated that a one-week manufacturing time would be ideal, as frail patients can develop kidney or liver dysfunction while waiting for their therapy or may become too weak for treatment. He has prescribed Gilead's Yescarta and Tecartus, as well as Bristol Myers' Breyanzi.
CAR-T drug use could expand by prescribing them earlier in the treatment process, before other treatments fail. For instance, J&J’s Carvykti was approved in April for patients who did not benefit from one other treatment for multiple myeloma. Some CAR-T approvals require patients to fail three or four other treatments before use.
Increasing the number of hospitals and health centers offering these treatments would also make them more accessible.
Since 2017, over 42,000 people worldwide have received CAR-T treatments. Six are approved in the U.S. for blood cancers, including lymphomas and some forms of leukemia.
Lynelle Hoch, who leads Bristol Myers Squibb's cell therapy business, said the current focus is on increasing manufacturing capacity. The time to produce treatments is trending lower, aided by collaboration with Cellares, which has a fully automated cell therapy production platform.
J&J stated it doubled its CAR-T manufacturing capacity last year and aims to double it again in 2024. The company is also working to reduce treatment times further.
Cindy Perettie, an executive at Gilead's Kite cell therapy unit, emphasized the urgency for lymphoma patients who have tried two treatments and have only months to live. "Every day matters for these patients."