There’s been a flurry of news in recent weeks regarding CAR-T.
That’s the groundbreaking cellular immunotherapy that oncology researchers say is a cure for certain types of leukemia and lymphoma and potentially several other cancers.
Few oncologists use the “C” word, as in “cure.”
That’s because most cancer treatments simply don’t live up to their early promise.
But CAR-T isn’t like most cancer treatments. This one could be the real deal.
In late-stage clinical trials, the treatment is showing results in cancer patients that researchers have simply not previously seen.
As a result, CAR-T is in unprecedentedly high demand by both patients and drug companies.
Two weeks ago, Gilead Sciences, the fourth largest pharmaceutical company in the United States, purchased Kite Pharma — the small biotech company whose specialty is CAR-T — for almost $12 billion in cash.
CAR-T, which stands for chimeric antigen receptor T-cell therapy, is a one-time infusion utilizing a patient’s own engineered T cells to fight cancer.
The entire process takes about three weeks.
Kite’s CAR-T candidate, axi-cel, is expected to receive approval from the Food and Drug Administration (FDA) in late November as a new treatment for patients with relapsed, aggressive, and nontransplant eligible forms of non-Hodgkin’s lymphoma.
With this purchase, Gilead, already a world leader in the HIV drug market, also becomes an immediate leader in the immunotherapy sector.
“We are limited in what we can comment on at this stage, as the transaction isn’t finalized, and while we are still operating as two separate companies,” Nathan Kaiser, associate director of public affairs for Gilead, told Healthline.
“What we can say at this point is that Kite has cutting-edge technology, and this transaction immediately places Gilead as a leader in cell therapy, which we believe will be the cornerstone of treating people living with cancer.”
First CAR-T treatment in the United States
Just days after Gilead purchased Kite, Swiss drug giant Novartis announced that Kymriah, its CAR-T candidate for children and young adults with acute lymphoblastic leukemia, was approved by the FDA for use in the United States.
Despite Kymriah’s $475,000 price tag, industry observers say the drug’s approval will boost an already surging sector.
It could also pave the way for more investment in other cell-based therapies and more clinical trials for a variety of cancers.
“This approval will open the floodgates for these kinds of therapy to be used in many different leukemias, lymphomas, solid tumors, myelomas,” Dr. Prakash Satwani, a pediatric hematologist-oncologist at Columbia University Medical Center, told Business Insider. “I think this is just the beginning of a new era of gene therapy.”
For the several large and small companies that have CAR-T therapies in trials, including Novartis, Juno Therapeutics, Kite Pharma, and Bluebird Bio, it was a race to see who would be first to cross the regulatory finish line.
While Novartis got there first, it’s expected there will be room for each of these companies’ treatments as they make their way to oncologists’ offices in a matter of a few years, or in some cases, a few months.
Success and setbacks
Therapies that harness the body’s own immune system are the hottest trend in cancer treatment in 2017.
And CAR-T is clearly the most effective.
The treatment is called a “living drug” because it involves putting altered cells back in the body that multiply and battle cancer.
CAR-T has been widely hailed as a game changer and likely cure for various blood cancers and multiple other types of cancer.
In the Novartis trial, which was populated by 63 leukemia patients who basically had no chance of survival with other treatments, 83 percent were in remission after three months, and 64 percent were still in remission after a year.
“CAR-T shows the unbelievable power of your immune system,” Dr. David Maloney, the medical director for cellular immunotherapy at the Fred Hutchinson Cancer Research Center, told CBS News.
However, not everyone who’s been treated with CAR-T achieves a complete response, or stays in remission.
This week, Robert Legaspi, one of the first patients in Kite’s CAR-T trial for acute lymphoblastic leukemia (ALL) at Moores Cancer Center at the University of California San Diego, told Healthline that his cancer has returned.
Legaspi was touted last year by researchers at Moores as someone who had fought ALL virtually his entire life and who may have finally found a cure in CAR-T.
In a Yahoo Finance story last year, he said he believed he was cured.
And his team at Moores agreed.
Dr. Januario Castro, principal investigator of the CAR-T studies at Moores, said last year that Legaspi was not only leukemia-free but “could potentially be cured from this deadly medical condition.”
But in an exclusive interview with Healthline this week, Legaspi expressed his disappointment that his cancer had recurred.
However, he added he was looking forward to being retreated.
“I’m still waiting for my team to plan it out,” he said. “They don’t have a clear answer to why it came back. But I trust my team. I know I can get over this.”
Legaspi knows he isn’t necessarily a typical CAR-T patient, and that many CAR-T patients are still in remission months and even years after their clinical trials.
He’s still a big believer in the therapy. He added he isn’t sure when the retreatment will begin, and that he’s currently “a little fatigued due to the meds.”
“I believe I might be the first one to redo it,” he noted.
The team of doctors at Moores Cancer Center who are working on the leukemia trial in which Legaspi enrolled declined to comment for this story, citing patient confidentiality.
“These questions relate to private information from patients,” Castro told Healthline in an email. “They have not consented for that process. Therefore, I cannot provide comments.”
Healthline also requested comment from Kite Pharma but got no reply.
The risks vs. the reward
For cancer patients who are considering CAR-T, the overriding question is: Are the rewards of the treatment worth the risks?
The answer remains an unequivocal “yes” for Legaspi and several other cancer patients interviewed by Healthline who’ve participated in CAR-T trials, or plan to.
The cancer patients who participate in CAR-T trials are typically out of options.
But amid the outstanding results of this treatment even in cancer patients who are very ill, there are risks to this procedure.
And there have been some sobering setbacks, and even clinical trial deaths.
The biggest risk to patients who are treated with CAR-T is something called cytokine release syndrome, which is described as a systemic inflammatory response caused by cytokines released by infused CAR-T cells.
Cytokine is any of a number of substances, such as interferon, interleukin, and growth factors, that are secreted by certain cells of the immune system and have an effect on other cells.
When cytokines are released into circulation, they can generate a host of symptoms, including fever, nausea, chills, hypotension, headache, rash, and scratchy throat.
The symptoms are typically mild to moderate and are managed easily. And they go away in just a matter of a couple weeks, which can make the treatment more tolerable than chemotherapy.
But some patients experience severe reactions that result from a massive release of cytokines. And it can lead to death if not quickly and properly managed.
The most recent report of a CAR-T-related patient death came during a trial, by French drug company Cellectis, of a novel CAR-T treatment that uses T cells from donors rather than from the patients themselves.
The FDA placed clinical holds on two early-phase trials known as UCART123, following the death of a 78-year-old man being treated for blastic plasmacytoid dendritic cell neoplasm (BPDCN).
According to OncLive, the man died after experiencing cytokine release syndrome.
Curing babies who have leukemia
Researchers in London say they have cured two babies of leukemia in what has been described as the world’s first attempt to offer CAR-T treatment with genetically engineered immune cells from a donor.
Technology Review reported that the experiments, which took place at London’s Great Ormond Street Hospital, address the viability of “off-the-shelf cellular therapy using inexpensive supplies of universal cells that could be dripped into patients’ veins on a moment’s notice.”
If this ready-made process ultimately proves to be safe, it would be much easier to administer than the CAR-T that is designed for each individual patient.
And it could potentially pose a competitive threat to Gilead, Novartis, Juno, and other companies that collect a patients’ T cells, engineer them, then reinfuse them.
CAR-T in China
CAR-T is gaining steam across the globe.
Several biotech companies in China, which is becoming a bigger player in the biotech space each year, have CAR-T treatments in various stages of development.
Some have begun clinical trials.
The Xinhua News Agency in China reports that a Chinese hospital has just used CAR-T to successfully treat a U.S. patient with myeloma, a cancer of the bone marrow.
This is the first time someone living outside China received CAR-T at a Chinese institution, according to the hospital.
Craig Chase, 56, from California, was reportedly discharged two weeks ago from Jiangsu People’s Hospital in Nanjing after receiving treatment.
Before he was discharged from the hospital, his blood test results were reportedly within normal range.
Safety and costs
The CAR-T technology is still in its infancy and has room for immense growth, as well as improvement in terms of safety.
Industry observers are confident that as pharma and cancer centers that are running CAR-T trials together learn to mitigate and regulate cytokine release syndrome and other potentially serious side effects, the product will become less risky.
Juno Therapeutics, for example, has quickly and proactively dealt with several patient deaths in its CAR-T trials.
Afterward, Juno announced that in a clinical trial for patients with relapsed and refractory aggressive non-Hodgkin’s lymphoma, its CAR-T candidate, JCAR017, provided a high rate of durable responses with no sign of cytokine release syndrome.
The other big issue for patients seeking CAR-T is its prohibitive cost.
The price of the newly approved Novartis CAR-T treatment is $475,000.
But Novartis is working with U.S. cancer centers to support access to the therapy and with insurance coverage by charging only those patients that respond to the cell therapy in the first month.
Advocates of the treatment say the price is high because the complicated and delicate CAR-T process is custom-made for each patient.
It requires that the patient’s T cells be sent to a specialized center where they are engineered to express a chimeric antigen receptor that prompts them to seek and destroy the so-called CD19 antigen found in cancerous B cells.
Do cancer patients understand these treatments?
Do American cancer patients yet have a good understanding of these technical, complicated new cancer treatments that use the body’s immune system to fight cancer?
Evidently, yes and no.
In a new survey from Inspire of more than 800 cancer patients who use Inspire’s patient engagement platform, most of those surveyed were familiar with the terms “immuno-oncology” and “immunotherapy,” Dave Taylor, senior director, head of research at Inspire, told Fierce Pharma this week.
But when it comes to specifics on how this generation of drugs works, the public’s knowledge drops down to 25 to 40 percent.
Cancer patients tell Healthline that it is the duty of oncologists and the pharmaceutical industry, as well as the media, to educate the public about these new cancer therapies.
Cancer patients interviewed by Healthline said their doctors also need to be honest with patients about both the risks and benefits of this treatment, and tell them about any potentially effective treatment even if it means the patient will go elsewhere for treatment.
One woman from the Midwest who recently finished a CAR-T trial for her non-Hodgkin’s lymphoma, but asked for anonymity because she did not want to upset her physician, said she told her doctor about CAR-T, not the other way around.
“Doctors need to be totally open and honest about this treatment, even if they think they might lose us as a patient,” she told Healthline. “And they need to tell us just what this treatment really is and how it works. CAR-T probably saved my life. Just be honest with patients. Tell us about all our options, that’s all we ask.”
CAR-T’s bright future
The future of CAR-T appears to be bright.
Industry observers almost unanimously agree that despite the potentially serious side effects and the high cost, CAR-T’s seat at the table of top cancer treatments is secure.
Gilead’s Kaiser noted that its newly acquired CAR-T candidate, axi-cel, coupled with Kite’s much-publicized state-of-the-art manufacturing capabilities and portfolio of next-generation therapy candidates, will serve as a substantial platform for Gilead’s efforts to build an industry-leading cell therapy program in oncology.
“We intend to rapidly accelerate the development of pipeline candidates, next-generation research and manufacturing technologies for the benefit of patients around the world,” Kaiser said.
In a conference call with investors after the announcement of the purchase of Kite, Gilead Chief Executive Officer, John Milligan, reportedly said the acquisition of Kite will “play out for decades to come as we continue to improve CAR-T and hopefully make cellular therapies a cornerstone for oncology treatment.”
Juno’s Chief Executive Officer, Hans Bishop, is equally optimistic about the future and about the coming diversification of this technology.
“We have a deep pipeline and trials underway for several indications, but we are of course very focused on bringing JCAR017 to market,” Bishop told Healthline. “Looking forward, we have a multiple myeloma trial under way with a second slated to begin later this year. We also have five solid organ tumor targets in trial, with more in the pipeline.”
Juno, too, is focused on the next generation of CAR-T products.
“We see real potential for CAR-T therapy beyond leukemia and lymphoma in multiple myeloma, and we also believe that there is potential to treat solid tumors,” Bishop said, “though there are some biological challenges that we will have to figure out.”
Bishop envisions CAR-T products that are not just more effective and safer, but that also replace today’s “brutal treatments like chemotherapy.”
“We really believe that cell therapy can transform cancer treatment,” Bishop said, “and ultimately change the standard of care in a way that not only saves lives, but restores quality of life for patients.”