For the first time, the Food and Drug Administration has approved a therapy that involves the science of a patient’s own cells, agency announced Wednesday.
The therapy, called Kymriah (tisagenlecleucel) by Novartis, will be used to restore the immune cells of children and young patients with a type of leukemia, called B-cell acute lymphoblastic leukemia. During the 22-day recovery from the body, the patients’ immune cells—especially the T cells that attack the body and destroy enemies—receive a new gene that allows them to recognize and attack leukemia cells.
Such therapies, called CAR-T therapies, have shown the ability to effectively attack back cancers in several trials, raising the hopes of researchers and patients alike. But they come with serious safety concerns—as well as serious price tags.
However, the FDA announced its approval with enthusiasm and optimism, calling it a “historic step.” In the announcement, FDA Commissioner Scott Gottlieb said:
“We are entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer. New technologies such as gene and cell therapies hold the potential to revolutionize medicine and create an inflection point in our ability to treat and even cure many chronic diseases. At the FDA, we are committed to helping advance the development and review of groundbreaking treatments that have the potential to be life-saving.”
Like all CAR-T therapies, Kymriah involves reprogramming T-cells to contain a gene that codes for a protein called a chimeric antigen receptor or CAR. This protein allows T cells to recognize and attack cells that have a protein called CD19 attached to them—which leukemia cells do.
In the Kymriah process, researchers first harvest T cells from a patient and then send them to a manufacturing facility. There, researchers insert the CAR gene into immune cells using a virus. The process takes 22 days, Creation reported.
“A New Year”
In the previous trial, 52 of 63 participants (82.5 percent) achieved overall remission after receiving the therapy. The trial was not published and had no controls, so it is not possible to determine Kymriah’s effect. But trials of other CAR-T therapies have shown similarly high rates of remission. And the initial results were enough to sway an external panel of FDA scientific advisors in July. In a unanimous vote on July 12, the committee recommended that the FDA approve Kymriah.
“This is a major advance and it takes a new era,” said committee member Malcolm Smith, an oncologist at the US National Institutes of Health in Bethesda, Maryland. tell him Creation at the time.
But, the story is not all rosy. CAR-T therapies are known to cause life-threatening immune responses called cytokine storm or cytokine release syndrome (CRS). This can lead to systemic inflammation, including organ failure, seizures, delirium, and brain swelling. Several trials of treatments similar to Kymriah have reported deaths.
In the Kymriah trial, 47 percent of patients experienced some level of CRS, but none died. Novartis reported that it was able to control all cases of CRS.
The FDA noted the risk in today’s announcement and also revealed that it has expanded the approved use of a drug called Actemra, which treats CRS, so it can be used in patients receiving CAR-T therapy. The FDA also approved Kymriah with a “risk evaluation and mitigation process” or (REMS). This includes additional protections such as additional training and guidelines for health care providers.
Right now, though, Kymriah is only approved for use in patients age 25 or younger who have failed conventional treatments or relapsed after receiving those treatments. Of the approximately 3,100 patients age 20 or younger diagnosed each year with acute lymphoblastic leukemia, about 15 to 20 percent will fail treatment. For these patients, Kymriah can be a real life-saver, as there are few alternatives.
But along with scary side effects, gene therapy can also come with a high price tag. UK experts have appraised one round of therapy $649,000. It is still unclear what the actual cost will be and what patients will end up having to pay.
Inside we click Release, Novartis announced that it is working with the Centers for Medicare and Medicaid Services to come up with “results-based pricing.” Also in the release, Bruno Strigini, CEO of Novartis Oncology, added:
We are very proud to be a part of this historic moment in cancer care and are very grateful to our researchers, partners, and the patients and families who participate in the Kymriah clinical program. As a breakthrough immunotherapy for children and adolescents who need new options, Kymriah truly reflects our mission to discover new ways to improve patient outcomes and the way we treat cancer.