The FDA on Wednesday opened a new era in cancer treatment, when it approved a landmark, futuristic new gene therapy-based approach to treat childhood leukemia, one which has produced unprecedented results in patients with the deadly cancer. Even the FDA called the approval "historic."
"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.
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 other tumors. The therapy is made by harvesting patients’ white blood cells and rewiring them to home in on tumors. Novartis’s product is the first CAR-T therapy to come before the FDA, leading a pack of novel treatments that promise to change the standard of care for certain aggressive blood cancers.
"This is a brand new way of treating cancer," said Dr. Stephan Grupp of Children's Hospital of Philadelphia quoted by the AP, 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."
This first use of CAR-T therapy is aimed at patients ill with a common pediatric cancer — acute lymphoblastic leukemia, or ALL — that strikes more than 3,000 children and young adults in the U.S. each year. While most survive, about 15 percent relapse despite today's best treatments, and their prognosis is bleak.
The therapy will be marketed as Kymriah.
The price tag: $475,000 for a course of treatment. While the amount sounds staggering to many patients, it was far less than many analysts had expected. Still, David Mitchell, president of advocacy group Patients For Affordable Drugs, met with Novartis yesterday to talk about "how to arrive at a fair price for its new CAR-T drug," but said the meeting was "disappointing."
While the treatment’s approval had been seen as a foregone conclusion for months according to Stat News, its potential price has been the subject of speculation and debate. On Wednesday, Novartis revealed that it would charge $475,000 for a course of treatment, a price Bruno Strigini, the company’s head of oncology, said would allow (a few very wealthy) patients to access Kymriah while providing Novartis a return on its investment. The cost is well below Wall Street analyst expectations, which reached as high as $750,000 for a dose. And it’s cheaper than the roughly $700,000 price tag that U.K. regulators said would be fair considering Kymriah’s benefits.
In an attempt to make the drug more affordable, Novartis said it was working with Medicare on a system in which the government would only pay for CAR-T treatment if patients respond within a month.
Meanwhile, trial results of the drug have shown unprecedented success: in a clinical trial, a single dose of Kymriah left 83% of participants cancer-free after three months, results oncologists have hailed as a major advance for patients with few other options. The most frequent side effect was an inflammatory storm called cytokine release syndrome, a reaction to CAR-T that can prove fatal in some patients but is commonly controlled with immunosuppressant drugs.
“I think this is most exciting thing I’ve seen in my lifetime,” said Dr. Tim Cripe, an oncologist with Nationwide Children’s Hospital, at an FDA meeting on Kymriah in July.
Being truly revolutionary, the therapy has the price tag to justify it: the reason for the sky-high price of every treatment, unlike well-understood pills and commonly injected biotech drugs, CAR-T presents a radical new paradigm for doctors, regulators, and payers. CAR-T treatment uses gene therapy techniques not to fix disease-causing genes but to turbocharge T cells that cancer too often can evade. Researchers filter those cells from a patient's blood, reprogram them to harbor 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.
It's a completely different way to harness the immune system than popular immunotherapy drugs called "checkpoint inhibitors" that treat a variety of cancers by helping the body's natural T cells better spot tumors, according to the AP. CAR-T cell therapy gives patients stronger T cells to do that job. For some 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."
It remains unclear how lucrative a business opportunity Kymriah presents. There are about 3,100 new cases of ALL each year, but roughly 70 percent can be pushed into remission by standard therapy. That could leave just a few hundred patients who might be eligible for Novartis’s therapy, casting doubt on whether the company can get an outsize return on what will be a substantial manufacturing investment. Bloomberg estimates that the gene therapy is expected to generate $111 million in 2018 revenue, reaching blockbuster status, and $1 billion in sales, by 2024
However, as Stat News points out, the potential of CAR-T - a hot research area across several drug companies - goes far beyond Wednesday’s approval. Novartis is developing Kymriah for use in lymphoma, and its pipeline includes other CAR-T therapies targeting an array of blood cancers. Kite Pharma, recently acquired by Gilead Sciences, is awaiting FDA approval for a lymphoma therapy and is, like Novartis, developing a bevy of cell therapies it hopes can treat tumors liquid and solid. Juno Therapeutics, which slipped into a third place after its lead CAR-T ran into safety problems, has a similar focus.
News of the CAR-T's approval sent the Nasdaq Biotech index surging to its biggest gain since June 21, up as much as 2.3%. Two-thirds of the 160 stocks in the NBI are higher, with six names making new 52-week highs: PRTK, SGMO, BIIB, EXEL, FOLD, MYGN, while the IBB, the iShares Nasdaq Biotechnology ETF, is within a few dollars of 18-month highs reached in late July.