The Wonders of Modern Medicine Come at a Cost

The rise of gene-therapy treatments may launch a new era in the history of medicine.

Developing a mechanism to use a patient’s own cells to combat disease has long been a Holy Grail for scientists seeking new therapies, a paradigm-shifting breakthrough that could lead to an array of treatments and even cures for everything from cancer and heart disease to diabetes and Alzheimer’s.

Even as we pursue this exciting new line of research, we must guard against two common tendencies. First is the understandable, but irrational, exuberance that accompanies such scientific breakthrough, marked by the belief that it will meet every expectation, and solve all our problems. If only science were that easy. Second is ignoring the stubborn reality that these breakthroughs are often extremely expensive, making tremendous demands on our time and resources. Science is not a zero-sum enterprise; it has constraints.

Consider CAR-T therapy, which became the first F.D.A. approved gene-therapy treatment for cancer in the United States in 2017. It is being used to fight some common forms of blood cancer, including acute lymphoblastic leukemia in children and young adults, and large cell lymphomas in adults. Michigan Medicine, which I oversee, was one of the first health centers involved in the clinical trials that led to FDA approval of the CAR-T therapy in leukemia and lymphoma.

The science is impressive. A patient’s blood is drawn and sent to a lab where the T-cells — a key part of the body’s disease-fighting immune system — are modified so that they can effectively target proteins that are unique to the cancer cells from that same patient. The modified cells are returned to the patient through a blood transfusion, delivered in just a few minutes. Like a vaccine in longevity and specificity, the modified T-cells remain in the body, ready to attack whenever the targeted protein appears.

This bullseye approach overcomes one of the great drawbacks of chemotherapy, an often effective, broad-brush approach that kills good cells as well as the bad.

Unlike chemo, which often involves months or even years of treatment that can result in a multitude of chronic side effects, CAR-T treatment is delivered once, without many of the side effects typically associated with chemotherapy.  

Although CAR-T is an approved treatment for selected cancers, it is still in its early stages of discovery. Clinical trials in acute lymphoblastic leukemia or lymphoma have been performed at Michigan Medicine, where we have treated approximately 20 patients with CAR-T therapy. In a recent CAR-T trial for patients with leukemia, 83 percent of patients, many of whom had failed multiple lines of other cancer therapy, responded to treatment.

To date, CAR-T therapy has focused on treating patients who have relapsed or failed initial therapy. We do not know how effective CAR-T therapy would be if offered earlier in a patient’s medical course. Finally, the long-term effectiveness of CAR-T therapy ­— both the durability of responses and toxicity — are unknown.  

One thing that is clear is the high cost of CAR-T therapy. Kymriah, the first FDA approved product, is priced at $475,000 per treatment; Yescarta, developed by Kite Pharma, is priced at $373,000 per therapy. Even if this approach delivers on its promise, we must recognize that it is likely to remain extremely expensive.

Medicine is not like other aspects of our technological age, where everything from cell phones to PCs inevitably get better and cheaper. One reason is that therapies like CAR-T represent the trend in medical innovation toward targeting smaller groups of patients with relatively rare conditions. This is the exact opposite of the newest gadget aimed at a mass market. And in most cases, expensive, novel therapies are adopted earlier and to a greater extent in the United States than in many countries. In essence, we are taking the economic risk to implement medical breakthroughs when costs are highest.

This is one reason healthcare is very expensive in the United States — now consuming about 18 percent of GDP. Indeed, our ability to treat once refractory disorders is one reason healthcare costs keep rising. New specialty drugs and treatments including CAR-T therapy will continue a trend in which about 5 percent of patients now account for about half of all health-care spending.

All of this raises questions at the increasingly pivotal intersection of medicine, politics, economics, and social policy. As we celebrate our great advances, we must also recognize the limits and costs of this new era in medicine.

Marschall S. Runge, MD, PhD, is Executive Vice President for Medical Affairs and Dean of the Medical School for the University of Michigan.