Kymriah: an (Expensive) Precision Medicine Breakthrough

Earlier this week, The United States Food and Drug Administration made history by approving the first ever gene therapy for the treatment of cancer. As is often the case with breakthroughs, however, the therapy will not be cheap.

Novartis’s Kymriah (tisagenlecleucel) — a chimeric antigen receptor (CAR) T-cell therapy, has been approved for use in patients aged 25 or younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. The drug is a pure example of precision medicine: an extremely targeted gene therapy capable of killing cancer cells with a high success rate. In the clinical trial on which the FDA based its ruling, 63 patients received a single dose of the drug, and 82.5% of them achieved remission.

The importance of the approval was enough to draw a statement from Scott Gottlieb, MD, the agency’s Commissioner.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” he said in the statement. “New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we’re committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving.”

Now, a price for the drug is known: $475,000 for a single infusion. The amount is within the range anticipated by oncologists, and Novartis characterized it as well below a price level that could be justified on cost.

“While both external and Novartis’ quantitative assessments of these values indicate that a cost-effective price could be $600,000 to $750,000, we recognize the importance of this paradigm-shifting therapy and are setting the price at $475,000 for this one-time treatment,” Dana Cooper, a spokesperson for Novartis, said in an interview.

The cost partly takes into effect the process of administering the drug. A precision medicine drug through and through, each dose is a customized treatment created with a patient’s own T-cells, which are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein—CAR—that directs the T-cells to target and kill leukemia cells that have a specific antigen on the surface.

Once the cells are modified, they are infused back into the patient to kill the cancer cells. The turnaround for that customization is about three weeks, according to Novartis, and will be done in one approved laboratory in New Jersey.

Adverse events can be serious, and 47% of patients experienced cytokine release syndrome, though it produced no deaths. Three patients did die within 60 days of infections.

The price may be high for CAR T-cell therapy, but it is important to weigh the costs against the potential benefits for patients, Gwen Nichols, MD, chief medical officer for the Leukemia & Lymphoma Society, said in an interview. When children and young adults have their whole lives at stake, it’s easier to justify the expense of this new treatment.

Without CAR T-cell therapy, the costs of care, including a potential additional bone marrow transplant, are already “outrageously expensive,” Nichols said. “The real question is going to come when this therapy is poised to be expanded into other patients who are older, and providing the chance for 60 or 70 years of [additional] life is not what you’re talking about, and then we’re really going to have some tough value questions that we should be prepared to ask.”

Elements of this story appeared previously in Cure and OncLive.