U.S. approves genetically engineering blood cells as childhood leukemia treatment

Opening a new era in cancer care, the U.S. Food and Drug Administration on Wednesday approved the first treatment that genetically engineers patients' own blood cells into an army of assassins to seek and destroy childhood leukemia.

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The CAR-T cell treatment developed by Novartis and the University of Pennsylvania is the first type of gene therapy to hit the U.S. market — and one in a powerful but expensive wave of custom-made "living drugs" being tested against blood cancers and some other tumours, too.

FDA called the approval historic.

"This is a brand new way of treating cancer," said Dr. Stephan Grupp of Children's Hospital of Philadelphia, who treated the first child with CAR-T cell therapy — a girl who'd been near death but now is cancer-free for five years and counting.

"That's enormously exciting."

CAR-T treatment uses gene therapy techniques not to fix disease-causing genes but to turbocharge T cells, immune system soldiers that cancer too often can evade. Researchers filter those cells from a patient's blood, reprogram them to harbour a "chimeric antigen receptor" that zeroes in on cancer, and grow hundreds of millions of copies. Returned to the patient, the revved-up cells can continue multiplying to fight disease for months or years.

'We're entering a new frontier'

Novartis said it would charge $475,000 US for the treatment, made from scratch for every patient. But, the company said there would be no charge if the patient didn't show a response within a month.

"We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer," said FDA Commissioner Scott Gottlieb.

This first use of CAR-T therapy is aimed at patients desperately ill with a common pediatric cancer — acute lymphoblastic leukemia — that strikes more than 3,000 children and young adults in the U.S. each year. While most survive, about 15 per cent relapse despite today's best treatments, and their prognosis is bleak.

In a key study of 63 advanced patients, 83 per cent went into remission. It's not clear how long that benefit lasts: Some patients did relapse months later. The others still are being tracked to see how they fare long-term.

Still, "a far higher percentage of patients go into remission with this therapy than anything else we've seen to date with relapsed leukemia," said Dr. Ted Laetsch of the University of Texas Southwestern Medical Center, one of the study sites. "I wouldn't say we know for sure how many will be cured yet by this therapy. There certainly is a hope" that some will be.

Most patients suffered side effects that can be gruelling, even life-threatening. An immune overreaction called "cytokine release syndrome" can trigger high fevers, plummeting blood pressure and in severe cases organ damage, requiring special care to tamp down those symptoms without blocking the cancer attack. Also Wednesday, the FDA designated a treatment for those side effects.

Each dose could take 3 weeks to make

For many acute lymphoblastic leukemia (ALL) patients, the new CAR-T therapy might replace bone marrow transplants that cost more than half a million dollars, noted Grupp, who led the Novartis study.

"I don't want to be an apologist for high drug prices in the U.S.," Grupp stressed. But if it's the last treatment they need, "that's a really significant one-time investment in their wellness, especially in kids who have a whole lifetime ahead of them."

Initially, Novartis' CAR-T version — to be sold under the brand name Kymriah — will be available only through certain medical centres specially trained to handle the sophisticated therapy and its side effects. Patients' collected immune cells will be frozen and shipped to a Novartis factory in New Jersey that creates each dose, a process the company says should take about three weeks.

While this first use of CAR-T therapy only is aimed at a few hundred U.S. patients a year — relapsed ALL patients up to age 25 — it's being tested as a treatment for thousands more. Kite Pharma's similar CAR-T brand, developed by the National Cancer Institute, is expected to win approval later this year to treat aggressive lymphoma, and Juno Therapeutics and other companies are studying their own versions against blood cancers including multiple myeloma.

Scientists around the U.S. also are trying to make CAR-T therapies that could fight more common solid tumours such as brain, breast or pancreatic cancers — a harder next step.

'We are exploring a more Canadian solution'

Today's FDA approval is important because it means this immunotherapy approach to cancer is finally ready for the clinic — to join surgery, radiation, and chemotherapy in the cancer fighting arsenal. But in practice, it won't change cancer treatment in the short term, especially not for Canadian patients.

Right now, the CAR-T therapy will only be available in specially selected centres in the U.S. which have been equipped and trained to do the complicated procedure of extracting a patient's cells, and genetically modifying them, reprogramming them to attack cancer, and then infusing them back into the patient's body. And the price tag of half a million dollars US, not including supportive care, will put the treatment out of reach for many patients and their families.

But a network of Canadian scientists are busy working out a made-in-Canada protocol that would be affordable for the public-health system. John Bell, scientific director of  BioCanRX and a senior scientist at the Ottawa Hospital, said his group is working to get the new CAR-T therapy infrastructure up and running in Canada.

"We hope to get a human trial going next year or early the following year using this exact strategy.

"There are two steps. First you have to manufacture the virus product which is used to reprogram the immune cells which are used in the therapy. We're in the throes of doing that now. The second step is to harvest cells from [the] patient, infect them with the virus and put them back in the patient. We hope to have that optimized and ready to go next year."

He said a major objective is to find a way to offer CAR-T that will be affordable to the Canadian health-care system.

"We are exploring a more Canadian solution where we can have it produced in our own institutes, and given like a bone marrow transplant which is not commercialized but simply done on a institute basis, to see if there's some way to do that and make these really important therapeutics available to Canadians."

At this point the therapy has not been successful against solid tumours. But Bell said his team is also working on that problem.

 "We were recently funded by the Ontario Institute for Cancer Research to combine this kind of therapy with virus therapy to see if those two combinations could be effective in solid tumours."

The Ontario Institute for Cancer Research is funded by the Province of Ontario.