For the second time in two months, remarkable recoveries from desperate cases of cancer have led to early approval of a cutting-edge therapy called CAR-T, which is made from a patient’s own genetically engineered cells.
More than a month before the decision was due, the FDA has given the nod to axicabtagene ciloleucel, now branded as Yescarta, to treat adults with desperate cases of non-Hodgkin lymphoma (NHL) who have failed at least two other treatments, such as chemotherapy. Ten cancer centers will be ready to treat patients immediately and more than 70 centers should be ready within a year, says David Chang, chief medical officer of Kite Pharma, the company that brought the complicated cell-based medicine to market.
The American Cancer Society estimates that 72,240 people will be diagnosed with NHL this year and 20,140 people will die from it. This type of lymphoma accounts for about 4 percent of all cancers in the United States. With CAR-T cell therapy, a patients’ T cells are extracted, shipped to a lab to become genetically modified cancer killers, then shipped back and infused into the patient. Kite’s manufacturing lab is in El Segundo, CA, near Los Angeles. (CAR stands for chimeric antigen receptor, the main genetically modified part of the cell.)
Gilead Sciences (NASDAQ: GILD) of Foster City, CA, which specializes in medicine for HIV and hepatitis C, bought Kite for $12 billion in August to jump-start its cancer business. Gilead said today that axi-cel, as the Kite CAR-T is also known, will cost $373,000.
Santa Monica, CA-based Kite, now a division of Gilead, has hinted for a while that axi-cel could do what other CAR-T programs have failed to do: become a more effective cancer killer the longer it stays in a patient’s body. The first window into that potential comes with today’s approval.
The drug’s official label lists data that Chang says were compiled from patients nearly nine months after they received their one-time dose of cells. Of the 101 patients, 72 percent showed some kind of positive response, and 51 percent had a complete response—that is, no sign of cancer.
Those rates are remarkably better than the snapshots taken of the same patients three and six months after treatment. Those data, which Xconomy described here and here, showed axi-cel wiping out cancer in roughly 40 percent of patients. In other words, some patients did not see a benefit from the treatment until many months after they received their dose, a sign that the souped-up cells stayed alive and vigilant for their target—in this case, lymphoma cells with the protein CD19 on their surface.
But that vigilance, which makes T cell therapies so promising, also has a price. Axi-cel has produced some of the severe side effects that have haunted other versions of this new, powerful kind of cancer medicine.
The FDA has required a “black box” warning about the side effects—mainly an immune system overdrive called cytokine release syndrome and neurological problems such as seizures, headaches, and delirium. One person has died from cerebral edema—swelling in the brain—which Krishna Komanduri, director of the adult stem cell transplant program at the University of Miami’s Sylvester Comprehensive Cancer Center, calls “the most feared complication” of CAR-T. Kite said in April that the patient was “very sick” with “explosive” rapidly progressing NHL.
“Fortunately cerebral edema appears to be relatively rare with this product, though the causes of this potentially fatal condition are still poorly understood,” says Komanduri, who was an investigator in Zuma-1, the main study that led to axi-cel’s approval.
For other CAR-T products, including the first ever approved, tisagenlecleucel (Kymriah) from Novartis (NYSE: NVS), the cells have been most effective within one month, then in some patients the cancer claws its way back. But those results have come in a different type of cancer: acute lymphoblastic leukemia. (This is why CAR-T researchers at Seattle Children’s, whose first experimental CAR-T product has saved several young patients’ lives, are working on a host of next-generation CAR-T models, as Xconomy recently reported.)
Armin Ghobadi, an assistant professor of medicine at Washington University and also one of the investigators in the axi-cel clinical trial, says that the cytokine response is better understood now and can be mitigated, but the brain complication that could arise from the therapy still needs more research. Nonetheless, Ghobadi says he is excited to be able to offer another option to patients who have failed chemotherapy.
“This is going to change how we treat blood cancers, and how we treat cancers in general,” he says.
Axi-cel was developed by the National Cancer Institute and then Kite. It is meant to be a one-time treatment. There is some game theory behind the pricing. Tisagenlecleucel is for kids and young adults with a severe form of leukemia, and it comes with a $475,000 price tag. Like axi-cel, it is a single dose.
Kymriah could also be approved in coming months for adults with NHL and compete with axi-cel. Novartis said it would consider a different price for NHL—an unusual move in the biopharma world.
For pediatric leukemia, Novartis has also pledged to waive the cost for patients who do not respond to the treatment within a month.
Novartis said it chose that threshold for two reasons: to be “in line” with billing and insurance practices, and because those data—how well patients fared one month after treatment—are the only clinical data in the drug’s label.
But Gilead has not set any alternative price mechanisms with axi-cel for NHL, even though more than half of patients in the key study had not responded to the treatment within six months. A Gilead spokeswoman says the company is in ongoing and active discussions government and commercial payers, and there are “varying degrees of interest and ability to execute value-based agreements.” In December, Kite officials will present the results of the same patients 12 months after receiving axi-cel. If the upward trend shown today continues, the price setters at Gilead might feel that no performance contingencies are necessary.
Frank Vinluan contributed to this report.
Image of T cells attacking cancer via the National Cancer Institute/Duncan Comprehensive Cancer Center at Baylor College of Medicine.