Since the FDA approved the first CAR-T therapy back in August 2017, high prices, small patients pools and limited manufacturing capacity have at times hindered these cell-based treatments. As biopharma companies clear those hurdles, a larger, more systemic problem now threatens the drug class.
Six CAR-T therapies targeting either CD19 or BCMA have reached the U.S. market to treat various blood cancers. Impressive efficacy data, wide reimbursement acceptance, earlier-line approvals and steady production expansions have fueled blockbuster revenue predictions. But drug developers and Wall Street may have underestimated the bottlenecks from the healthcare infrastructure needed to deliver a cell therapy, Leerink Partners analyst Daina Graybosch, Ph.D., warns.
CAR-T therapies are indeed on a fast trajectory of growth. By 2027, when the drug class celebrates its first decennial anniversary, Johnson & Johnson expects its Legend Biotech-partnered Carvykti—the last of the six existing CAR-T products to hit the market—will have reached about $4.5 billion in annual sales. As J&J noted during a December presentation, its estimate is 25% above analysts’ consensus. Bristol Myers Squibb and Gilead Sciences’ Kite Pharma (though a collaboration with Arcellx) both have high hopes for their rival BCMA-targeted CAR-Ts, as well.
But the way in which community doctors refer patients to designated treatment centers and the scale of hospital infrastructure will likely not support some of the most bullish growth projections for CAR-Ts, Graybosch predicts.
“Hospitals across the United States are already overflowing, they’re already filled, emergency rooms are packed. And if CAR-T cells become more mainstream and as earlier lines of therapy, it will just add to the hospital burden,” David Porter, M.D., director of cell therapy and transplant at Penn Medicine, said in an interview.
The infrastructure bottleneck will likely manifest mid-decade, Graybosch said. Solving it will require hospital investments that significantly exceed the current pace, a “revolutionary paradigm shift” in cell therapy delivery, and time to make amends—a long time.

Having recognized the growth hurdle for CAR-T therapies, Gilead's Kite Pharma is adjusting its business setup to match the market reality. (Nuthawut Somsuk/iStock/Getty Images Plus)
A concerning early sign
 
Back in 2015, Graybosch raised this hypothesis in her first CAR-T research project. Now eight years later, the first signs of a growth snag have cropped up at Kite, the world’s largest CAR-T manufacturer. The cell therapy specialist’s CD19-targeted Yescarta delivered $391 million in third-quarter 2023 sales, which missed analysts’ expectations by 6%.
The disappointment came just over a year into the large B-cell lymphoma (LBCL) drug’s key expansion as a second-line therapy, which is supposed to more than double its eligible patient population. It also followed a landmark showing in early June, when the phase 3 Zuma-7 trial linked Yescarta to a 27.4% reduction in the risk of death versus the traditional second-line treatment.
Kite, having realized a misalignment between market reality and its business setup, launched an organizational overhaul to cut about 7% of its workforce.
“A big part of it comes down to the way the U.S. healthcare system is structured—it’s fairly fragmented,” Kite’s global head of commercial, Warner Biddle, said in an interview with Fierce Pharma.
Well over half of LBCL patients start their treatment journey in community health systems, and that’s where many got stuck, Biddle explained.
Because of complex treatment processes, CAR-T therapies are currently only offered at designated treatment centers. Patients who see a community doctor will need a referral to get CAR-T. Logistical challenges, lack of education and availability of alternative treatments have stopped patients from getting referred and benefiting from CAR-T.
To make CAR-T therapies, the patient’s own T cells are extracted during a two-day process called apheresis. Manufacturers then alter the cells for weeks before sending the final product back to the facility for treatment. After the infusion, patients are required to stay near the treatment center for a month to monitor for potentially life-threatening side effects.
That one-month monitoring requirement presents the biggest logistics challenge for most patients, Graybosch noted. Besides the cost of accommodation, many people can not afford to pack up their lives and live in a new place, Porter said. What’s more, even in large cities like New York, not all hotels are fit to host CAR-T patients. Sometimes, nurses and doctors need to work with the hotels to make sure they have everything the patients may need.
Community doctors may think about the logistics challenge of a CAR-T with or without their patients’ input, Graybosch noted.
“They don’t want to burden their patients with that until it’s absolutely necessary,” she said

https://www.pharma.com/pharma/mid-decade-crisis-looms-car-t-cell-therapy