Draw blood from someone with cancer. Engineer their blood cells to seek and destroy cancer. Reinfuse the cells and watch the cancer melt away. Chimeric antigen receptor T cell therapy (CAR-T) sounds like science fiction. But it’s the next frontier in cancer therapy.
We’re weaponizing individuals’ immune systems to destroy cancer and add years to their lives. It’s incredibly exciting. But at hundreds of thousands of dollars per dose, insurance companies and the U.S. government are struggling to figure out how to pay for these breakthrough treatments.
High prices not only pose a challenge to patient access, but they also raise a fundamental question: Are we creating these therapies the wrong way?
CAR-T immunotherapy is being tested for a range of cancers, and now holds the potential to benefit more than 1 million Americans who live with or are in remission from blood cancers. A single dose typically costs around $400,000. What makes the price so high? Having drug corporations make the cells.
Under the current system, a hospital extracts blood cells from a patient and sends them to a drug company’s manufacturing plant to be genetically engineered. It takes the company two to six weeks to engineer the cells, increase their number, perform quality and safety tests, and ship them back to the hospital to be reinfused into the patient. Under this system, there have been well-documented problems with the engineering process, as well as with shipping and handling.
There’s a better way, one that will lower the price, enable more precise and individualized targeting for specific patients, and allow for a faster process: Let medical centers do this.
Long before pharmaceutical companies took control of CAR-T, medical centers made these treatments. Cancer centers like the University of Pennsylvania, the National Cancer Institute, Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center, Baylor University, and others figured out how to engineer CAR-T cells and ran the initial trials to test them. Drug companies were later involved mainly as a means to scale up production.
There are clear advantages to keeping CAR-T treatment in medical centers, closer to patients.
First, academic medical centers are well-equipped to make these therapies. They already safely handle stem cells every day. They also routinely perform autologous stem cell transplants (these use a patient’s own stem cells), which require in-house doctors and specialists to preserve and protect stored blood cells, wash and radiate them if needed, and sometimes select cell populations for clinical use.
Hospitals and academic medical centers can accomplish the CAR-T process more quickly because they do not need to ship cells to and from a drug company plant. This is a critical issue, because most patients currently treated with CAR-T have not responded to other treatments and their health is seriously compromised; some patients die between the time stem cells are removed from them and the time they’re supposed to come back to the hospital for re-infusion.
Second, there are different regulations around stem cells than there are for drugs. That means CAR-T therapies created at hospitals and academic medical centers would not have to go through the yearslong FDA regulatory process. And the treatments developed would allow hospitals to target more effectively and quickly each individual’s specific cancer, which is off the table in the current system. Patients with advanced cancer do not have the luxury of time. Although this paradigm shift would require greater regulatory flexibility from the FDA, it would make CAR-T therapy far more effective.
Experience making CAR-T in leading medical centers show that locally engineered CAR-T cells can be made for less than half of what they are currently priced by pharmaceutical companies. We know this is possible because Switzerland is already doing it this way, and pricing CAR-T therapy between $150,000 and $200,000. Multiply that by the 10,000 individuals in the U.S. with the types of cancer for which CAR-T therapy is currently approved and we would save almost $2 billion a year. Factor in future CAR-T approvals and we will save many times that amount.
Making this change requires bucking the system. It means the FDA must redefine CAR-T from a drug to the autologous blood product it is. It’s a move that would save not only money but lives because it can target cancer better and destroy it faster.
We took a fork in the CAR-T road a few years back and went the wrong way. There is still time to change course for the good of the many Americans who need this lifesaving treatment.
David Mitchell, who is living with incurable blood cancer, is the founder of Patients for Affordable Drugs. Saad Kenderian, M.D., is a physician-scientist and assistant professor of medicine and immunology at the Mayo Clinic in Rochester, Minn. S. Vincent Rajkumar, M.D., is a hematologist and professor of medicine at the Mayo Clinic. The views expressed are the authors’ personal views and do not necessarily reflect the policy or position of the Mayo Clinic.
It might be a good idea provided every “t” is crossed and every “i” dotted. Big elephants pharma companies will make sure their cash cows are not disturbed, regulators don’t have enough staff to monitor these facilities.
Hospitals and university pay scales will also stand in the way.
Legislators and legalized corruption will also stand in the way.
Good ideas but reality is different from dream.
AgainTWO BIG GORILLAS , pharma and PBMs will not let it happen for sure.
Not being negative but realistic.
It may seem I am bei
Also what works on the lab scale does not work on production scale. Cost might not be be criterion initially but would have to be considered.
I have heard about this same topic so many times, and not once I’ve seen any thoughts towards the actual root cause of this problem, the ridiculously obscene prices of healthcare.
The price tag is based to cover insurance costs, and not the actual manufacture of cells.
The day we all stop and look at insurance companies and their completely inflated pricing, it’s when we will make some sense out of this.
If it can be done in Switzerland (with its very stringent rules) – then why would it not be possible in the US? But rather than in multi-function money-gobbling academic hospitals, perform these therapies in specialized CAR-T clinics. Would this not draw the right professionals, and deliver the greatest level of controllable reliability, at most reduced cost?
Most academic centers refuse to permit FDA review of their laboratory developed tests, even though many have been shown to be inaccurate. Before the academic centers start manufacturing, they should be willing to obtain federal review of what they are already doing. Having professional societies substitute for FDA review is not the way to go. Same with manufacturing. A lot can go wrong, and often the entity doing the work can see that about themselves. FDA has had to step in for tissue banking and other cell therapies when the academics were not doing a good job. Do not increase the problem.
If you deliver these therapies in a well-trained community cancer clinic, you can save 30-50% of the cost of CAR-T therapy in an ‘academic hospital.’ Your discussion fails to recognize this striking cost disparity. Juno’s CAR-construct seems we’ll suited to predominantly outpatient care.
I’m a senior regulatory consultant who recently completed a BLA -commercialization project, and have to take issue with a couple of your assertions. I know for a fact that at least in one case the time alloted for shipping, receipt and Quality release for leukocytes collected at a center to start of manufacture cannot exceed 48 hours. Further the greatest amount used in manufacture is the cell expansion process which can take up more than three weeks regardless of where it is done. Additionally The character of this process is far more complicated than the in-hospital act of leukocyte separation and is governed by U.S.CFR 21 610. The standards are significantly higher therefore and no matter who carries out Car T cell manufacture those standards have to be met. A good portion of the cost of CAR T cell manufacture goes to meeting the FDA’s rigorous Quality standards that ensure reproducible safety and potency for every patient. This includes extensive analytical test development. Each Car T cell therapy product is unique and therefore this test development goes on for each new product. The issue of whether prices of CAR T cell therapies are too high (and I think they probably are) can’t be solved by a do it yourself approach .
What the authors actually mean when the mention the FDA “be flexible”is that that the FDA would have accept a lower safety standards for manufacturing and contamination risk at academic medical centers than what is approved now. There is also no guarantee that CART made at different hospitals would be interchangeable and have the same clinical efficacy. This would have to be established in randomizes clinical trials-not just because the authors state that academic centers will be better.
The NIH of all places was not able to maintain appropriate manufacturing controls and was shut down for fungal contamination in 2015.
Academic centers should be held to the same standards as Industry- the idea that Academic centers can take more risks and be held to lower in manufacturing quality just because they are academic centers will never be accepted by the FDA and probably isn’t legal. There is no carve out in the FDA authorization Act that academic centers can be held to lower standards just to save money.
@ Authors You didn’t mention in your essay what is preventing hospitals from doing this, which is central to your argument. If it would be cheaper and better, why can’t hospitals just get approval to manufacture just like any other company would?
They do. What they mean by “flexibility” is a lower bar for manufacturing standards at academic centers and the assumption (without clinical trial evidence) that CART therapies produced at any center would be interchangeable.
Good luck with that!
The whole system is designed to profit on diseases, so I strongly doubt there is the will, or even the legal way to do that.
As an example, take Amifampridine, and Vincristine, two simple chemicals, off patent, costing literally a buck per dose. And yet, hospitals seems incapable (more likely unwilling) to buy them in bulk from chemical suppliers, and simply dosing them. And, saving hundreds of thousands of dollars in the process.
I concur. Healthcare in the US and likely worldwide is a multibillion dollar industry, none depending on prevention of disease. There are so many cancers, caused by viruses that are preventable by vaccine, yet we see only one. The knowledge about the role of HPV, for example, had been known in academia, yet it took >40 yrs for a vaccine! The whole Herpes virus group are cancer-causers, and yet again, no vaccine is planned. The mononucleosis virus Epstein-Barr is also a killer. It causes Hodgkins disease, Burkitts lymphoma, and several others. Yet again, no vaccine. The only reason, I am told, that Merck even produced the HPV vaccine is that they were”embarrassed” by a drug they produced that caused several unexpected deaths, so they were trying to do damage control for their reputation
It is more lucrative to treat than to beat. How unconscionable! The biggest mistake is allowing the “money-changers” to run healthcare. Now there are more in offices sitting at their desks than are those dedicated personnel in the trenches.
@dipthroat Interesting point on the HPV vaccine. I wonder, why can’t a company make more money on prevention than treatment? If I can sell a treatment for $30k, why can’t I sell a prevention for $100k? I would certainly pay more to avoid cancer than to treat it.
My guess is that people don’t know how (and are too busy) to price risk, and hence don’t spend money on prevention when it is in their interest. Think smoking and lung cancer. It costs nothing to prevent, but people still smoke and pay big money for lung cancer treatment.
The kicker is, if you don’t know how to price risk, who can you trust to do it for you? Certainly not the company selling the treatments!
I think it’s a great idea! However, it’s all about the money. If reimbursement is comparable, maybe. Setting up a protocol to do this “in-house” may be more costly in finding skilled staff, lab space and supplies, etc. Cost per test may be less when referenced to a lab that does many per day.