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Chimeric antigen receptor (CAR) T-cell therapies have led to a revolution for certain cancers that otherwise would have limited treatment options. The high costs, however, present a major obstacle for patients, healthcare providers, and payers.

As explained in a review in the , ensuring a fair price for CAR T-cell therapies and increased access to these potentially life-saving therapies will require a multipronged combination of strategies, including price negotiation, innovative manufacturing approaches, and the implementation of alternative payment models.

Edward R. Scheffer Cliff, MBBS, MPH, of Harvard Medical School and Brigham and Women's Hospital and Dana-Farber Cancer Institute in Boston, and co-authors addressed the issues of the extremely high prices of CAR T-cell therapies and how to make them more accessible and affordable.

In the following interview, Cliff, who is a postdoctoral research fellow at the Program on Regulation, Therapeutics, and Law, Division of Pharmacoepidemiology and Pharmacoeconomics, at Brigham and Women's, elaborated on key points in the review.

What factors contribute to the high manufacturing costs of CAR T-cells?

Cliff: The largest cost is personalized therapy with currently autologous products. The process of getting the patient in for apheresis, working on the person's cells from start to finish, and infusing them back into the patient is more expensive than making an off-the-shelf product.

The time required to make the cells through a number of steps is what contributes to costs. Allogeneic products may get around the costs of personalization. Pharmaceutical companies and academic centers will figure out how to improve manufacturing through automated steps.

Why is it so difficult to determine the true cost of manufacturing autologous CAR T-cells?

Cliff: CAR T-cell pioneer Carl June, MD, of the University of Pennsylvania, estimates that the manufacturing cost is 20K per person in the U.S. An Indian group working on CAR T-cells said it was able to manufacture a product for 35K U.S. per person. A Spanish group that issues funding for commercial CAR T-cells in academic centers developed a robust manufacturing process that cost 89K Euro, or 95K in U.S. dollars, per person.

The price for CARs now is 400K and up in the U.S. and 200-250K in Europe. Then there are hospital costs of 400-600K, so the total is 1 million for one patient in the U.S. Both manufacturers' price and hospital costs can be targeted to be lowered.

How could negotiating billing agreements between hospitals and payers reduce the price?

Cliff: This is a logistical and financial challenge. Typically, CAR T-cells were billed as a bundle of care, like a transplant. At first, they were only in-patient procedures. Now they are safer, and increasingly centers are doing it on an outpatient basis. Billing negotiations are an evolving topic, and outpatient CAR T-cells could substantially bring down costs, but we don't know yet if there will be a cost savings.

To be cost-saving, allogeneic CAR T-cells will have to be effective. Manufacturers will have to convince clinicians they are as good or better products. If they meet that bar, they could potentially bring down costs.

This partly depends on how much companies choose to price-out allogeneic CAR T-cells. Companies need to say they are not going to market allogeneic CAR T-cells for clinical reasons but for cost reasons.

Companies in the U.S. do not commonly use price as a negotiating tool. An off-the-shelf product clearly could be less expensive to make, but it's difficult to know by how much. Scientists who make CAR T-cells for research are convinced that can be less costly and that should translate commercially.

How could alternative payment be implemented?

Cliff: One approach is outcome-based payment -- that is, pay only a proportion of the fee unless the patient responds. For example, a 30% fee would be paid on CAR T-cell infusion and 70% for an ongoing response at day 100. A few states, including Oklahoma and Massachusetts, have outcome-based payments in place.

Then there's the so-called Netflix model, now available in Louisiana and Australia, for hepatitis C drugs. Companies pay a fixed price per year in return for an unlimited supply of hepatitis C drug. This works for hepatitis C because if an injection drug user gets hepatitis C again in 6 months, the cost is zero. For CAR T-cells, if only 30% of patients are cured, then the other 70% of the cost is saved because of the paid fixed price.

The biggest challenge is getting manufacturers on board. A payer with enough leverage may convince a manufacturer to use a novel payment method. We need to make novel payments more attractive to manufacturers.

How can clinicians make informed decisions about the value of CAR T-cell therapy relative to other treatment options?

Cliff: CARs are curative in ALL [acute lymphoblastic leukemia], pediatric ALL, and diffuse large B-cell lymphoma. In the curative setting, at a clinical level, the value is clear. For myeloma, where CAR T-cells are not curative, the question is how to sequence therapy that includes a CAR T-cell and which patients should receive it.

If a myeloma patient receives a bispecific antibody for 3 months and doesn't respond, then you have paid for the drug for only 3 months. If the patient receives a CAR T-cell and has no response, you have paid the full amount. Clinicians have to think about the financial toxicity of drugs and what systems to put in place to limit financial toxicity for the patient.

What is your main message for practicing oncologists?

Cliff: We need an increased discussion about the inequity of access and financial toxicity in prices of cancer drugs, including CAR T-cells. We need a multipronged approach to bring prices and manufacturing costs down, and more transparency in hospital billing.

CAR T-cells are a transformative cancer therapy, but only if patients can access the therapy. That includes timely referral to a CAR T-cell center and logistical support. If the process moves faster, we can reduce the costs.

Read the review here.