Cancer breakthrough near FDA approval carries costly side effect

A breakthrough cancer therapy that can wipe out leukemia in some deathly ill children and young adults comes with an expensive, long-lasting side effect.
The blood cancer treatment, called CAR-T, is made by Novartis AG and is on the brink of approval after a panel of advisers to the US Food and Drug Administration backed it on Wednesday in a 10-0 vote. It’s highly effective: In a clinical trial of patients who’d mostly run out of treatment options, 83% of patients who took it saw their disease go into remission.
Yet it also causes collateral damage. Novartis’s therapy commandeers the body’s immune system to destroy the cells where the blood cancer begins. Those cells, however, also make antibodies that fight off other diseases. Every patient whose cancer was wiped out in the study also contracted a condition called B-cell aplasia, which must be treated with drugs that can cost tens of thousands of dollars a year.
“The therapy is being given to people who would be dead if they didn’t receive it, and they would be dead within a pretty short period of time,” said Edmund Waller, director of Emory University’s stem cell and immune therapy division. They patients now have chronic immune system conditions, he said, “but they are happy to be alive.”
Neither the cancer therapy nor the follow-up is cheap. CAR-T treatments under development by Basel, Switzerland-based Novartis and several other companies are expected to cost $500,000 or more, partly because they’re tailored for each patient, genetically manipulating their infection-fighting T-cells to destroy acute lymphoblastic leukemia, a form of blood cancer.
Costly infusions
To prop up the patient’s crippled immune system, an injection of immune-boosting immunoglobulin is needed every three to four weeks as long as the altered cells remain in the body, Novartis said in a statement. Those treatments can cost as much as $10,000 a dose, and may be needed for life.
Immunoglobulin is already a big business generating about $8 billion in sales a year for drugmakers including Shire Plc, CSL Ltd., and Grifols SA. The antibodies are spun out of donated blood, and infused into patients, whose risk of infection quickly returns to normal levels.
Insurance companies said their decision to cover Novartis’s treatment and any follow-up therapy will be based on the clinical results of the drug.
“While CAR-T is a promising new type of immunotherapy, it is not commercially available and we have yet to complete our evaluation,” said T.J. Crawford, a spokesman for Aetna Inc. “Coverage determination will be made on clinical grounds.”
There is little dispute among experts over the therapy’s promise.
“This is probably the most exciting thing I have seen in my lifetime,” said Tim Cripe, chief of hematology and oncology at Ohio State University’s Nationwide Children’s Hospital. Cripe was a member of the FDA advisory panel that voted Wednesday to support the drug’s approval.
Panel members did raise questions about the long-term safety and potential complications, including infections and new cancers that could arise years after treatment. Novartis has pledged to track patients for 15 years for any safety issues.
Novertis’s CAR-T would be used in patients age 25 and under whose cancer comes back after chemotherapy — about 600 people a year in the US Acute lymphoblastic leukemia is the most common cancer in children. About 85% are cured by chemotherapy, but those whose cancer returns have few options.
The complication doesn’t apply universally across all CAR-T products, and newer generations now in development appear able to avoid the permanent destruction of B cells. Kite Pharma Inc., which has already applied for FDA approval of its rival therapy to treat a more common cancer known as diffuse large B-cell lymphoma, said it hasn’t been an issue. The company hasn’t disclosed how many patients in its trials needed immunoglobulin after treatment.
Makers of immunoglobulin are reluctant to talk about the issue, since their products aren’t approved for patients who develop secondary immune deficiencies that are a complication of another medical condition or treatment. The production process is complex, and shortages can develop. That could create problems if demand surges because of Novartis’s cancer treatment.
“It is not uncommon for the companies who make these products to manage supply closely,” said Elizabeth Kalina, a spokeswoman for Shire, which is building a new manufacturing facility that’s slated to open in Georgia in 2018. “Shire continues to explore ways to address patient demand today and as it looks toward the future.”
Costly drugs
Immunoglobulins like Gammagard, made by Shire’s subsidiary Baxalta, can cost $1,000 to $10,000 per injection, based on a patient’s weight.
While the permanence of the manipulated cancer killers is good for eliminating the blood malignancy, it’s bad for the immune system.
“Even if there was disease that pops up later, the CAR-T cell could still eliminate it. But the normal B cells are also being eliminated,” said Emory’s Waller. “It’s bad that it might be permanent.”
Kite’s therapy also hurt the antibody-producing B cells, but they came back. The company said that in its clinical trials, it was able to detect CAR-T cells in patients who respond to therapy for as long as six months, with recovery of normal B cells taking from a few months to more than one year, said Christine Cassiano, a spokeswoman for the Santa Monica, California-based company. The recovery of B cells may occur in patients who continue to respond to therapy, even after their CAR-T cells have declined, she said. 


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