More of these treatments have been approved, but supply chain issues and cost remain obstacles.
CAR-T therapies are a new and promising treatment for cancer. The global market for CAR-T therapies is projected to increase from $2.9 billion in 2020 to $11.8 billion by 2025, according to MarketsandMarkets.
But some major obstacles loom ahead, cost being one of them. A single CAR-T treatment can run into the hundreds of thousands of dollars. Although CAR-T therapy is a relative rarity now and therefore not a huge burden on payers, as the number of patients receiving it increases, so will the cost and payer scrutiny. The enthusiasm about the promise of CAR-T is also tempered somewhat by the risk of cytokine release syndrome, an adverse effect that can be life threatening.
CAR-T therapies involve genetically engineering a patient’s own T cells so they recognize and kill tumor cells.
Approved by the FDA in 2017, Kymriah (tisagenlecleucel) was the first CAR-T therapy to get the agency’s OK. Yescarta (axicabtagene ciloleucel) was next, approved a few months later as a treatment for large B-cell lymphoma in adults after at least two other kinds of treatment failed.
In 2021, the agency approved Abecma (idecabtagene vicleucel), the first CAR-T for multiple myeloma. And in February 2022, the FDA approved a second CAR-T therapy for multiple myeloma, Carvykti (ciltacabtagene autoleucel).
Sankalp Sethi, the cell and gene therapy practice lead at ZS Associates, has helped more than 25 oncology manufacturers commercialize cancer innovations and notes that this approval marks a strong gain in efficacy outcome.
“Nearly all patients (98%) in the study of Carvykti achieved a clinical response, and 78% achieved a stringent complete response,” he says. “Time is needed to determine how the product impacts overall survival, though many say that these results represent a new gold standard in CAR-T efficacy.”
Abhinav Deol, M.D., a hematologist-oncologist at Karmanos Cancer Institute in Detroit, says the recent spate of CART-T approvals is notable. In addition to Carvykti, the FDA approved Yescarta as a treatment for a broader group of patients with large B-cell lymphoma, Kymriah as a treatment for relapsed or refractory follicular lymphoma and Breyanzi (lisocabtagene maraleucel) as a treatment of patients with large B-cell lymphoma.
Deol also points to the ongoing trials evaluating allogeneic CAR-T cells, which would be available “off the shelf,” replacing the complicated process that involves using the patient’s own T cells. “Additionally,” he says, “there are ongoing studies looking at rapid manufacturing of autologous CAR-T cell product, thereby shortening the time it takes to have the product ready for infusion.”
Deol explains that CAR-T therapy provides another option for an increasing number of patients with cancers that have come back despite multiple rounds of other types of treatment.
“Long-term data in diffuse large B-cell lymphoma in the third-line setting shows that about 30% to 40% of patients can have sustained remission after CAR-T cell therapy,” Deol says. “Heavily treated (patients with multiple myeloma) can have disease control for over a year after one infusion of CAR-T cell therapy.”
For many patients, CAR-T represents their best potential option at a key moment of treatment eligibility. However, availability has been limited.
“These advancements mean these products can be more safely administered, more patients will be able to receive them and patients will be able to receive them earlier,” Sethi says.
“Remember, when CAR-Ts first came out, only a select number of centers of excellence were certified to administer. Given the complex nature of the products as well as the serious potential (adverse) effects, there was a need for providers to build more experience with the products before allowing for wider distribution.”
Progress has been made in overcoming some of the chief barriers to access to CAR-T, says Sethi, which include traveling distance for patients, management of adverse effects and financial viability of the administering centers.
“We are now reaching a stage where access is much more widespread — at this time, 70% of the U.S. population lives within 50 miles of a center that administers a CD19 CAR-T,” he says. “Geographic access to these products will no longer be a major barrier for most patients.”
Additionally, providers have become more comfortable handling the adverse events that come with CAR-T, he says. This means that for the right patients, outpatient administration is possible. Patients can stay with their families and caregivers while being monitored, improving their quality of life.
A recent study by ZS Associates also found that around 90% of CAR-T providers today are profitable overall with CAR-T administration.
“When first approved, CAR-Ts negatively impacted treatment centers’ finances, as reimbursement rates and mechanisms were still being sorted out,” Sethi says. “But we are now seeing that these centers have been able to become profitable through better management of (adverse) effects, applying markups and manufacturer discounts, and where applicable, receiving hospital-specific Medicare reimbursement adjustments. As a result, we expect more providers to be able to scale their capacity over time and offer CAR-Ts to more patients in the future.”
Supply Chain Issues
The supply chain and manufacturing challenges of CAR-T are center stage in discussion today.
Maria Whitman, global head of the pharmaceutical and biotech practice at ZS Associates, notes that Carvykti launched with a more limited number of certified centers (32) and limited manufacturing slots. This means that although patients and providers are eager for these products, the benefit is limited to a very small proportion of patients deemed eligible.
“Looking forward, it is also a source of budding innovation in support of patients,” she says. “Limited capacity and commercial availability are not only a challenge for meeting demand, but for scaling accessibility.”
For instance, Novartis recently unveiled T-Charge, a next-generation CAR-T platform that is expected to develop the cancer-finding T cells in the patient’s body instead of in a cell culture, reducing manufacturing time.
Gracell Biotechnologies Inc.’s proprietary FasTCAR platform is currently being evaluated in trials in China, and the company claims it has “next-day manufacturing” capabilities.
“Manufacturing turnaround times have long been a barrier to broader accessibility of CAR-T, and these developments are a strong sign that we are moving toward a future where patients are no longer waiting weeks to receive product,” Whitman says.
The high cost of CAR-T is another obstacle. CMS announced in 2019 that Medicare would cover CAR-T, but some provider groups have expressed discontent with what they say are low rates.
“One important thing to note is the cost for these advanced therapies can lead to sticker shock,” says Deol. “But the cumulative cost of other cancer therapies over a period of time is very high too, and CAR-T therapy is generally a one-time cost.”