https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm
The U.S. Food and Drug Administration issued a historic action today making the first gene therapy available in the United States, ushering in a new approach to the treatment of cancer and other serious and life-threatening diseases.
The FDA approved Kymriah (tisagenlecleucel) for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL).
"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, M.D. "New technologies such as gene and cell therapies hold out the potential to transform medicine and create an inflection point in our ability to treat and even cure many intractable illnesses. At the FDA, we're committed to helping expedite the development and review of groundbreaking treatments that have the potential to be life-saving."
Kymriah, a cell-based gene therapy, is approved in the United States for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.
Kymriah is a genetically-modified autologous T-cell immunotherapy. Each dose of Kymriah is a customized treatment created using an individual patient's own T-cells, a type of white blood cell known as a lymphocyte. The patient's T-cells are collected and sent to a manufacturing center where they are genetically modified to include a new gene that contains a specific protein (a chimeric antigen receptor or CAR) that directs the T-cells to target and kill leukemia cells that have a specific antigen (CD19) on the surface. Once the cells are modified, they are infused back into the patient to kill the cancer cells.
Also at NPR, CNN, BBC, and FierceBiotech.
Novartis press release.
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The U.S. Food and Drug Administration (FDA) has approved a gene therapy for non-Hodgkin's lymphoma (blood cancer):
The Food and Drug Administration on Wednesday approved the second in a radically new class of treatments that genetically reboot a patient's own immune cells to kill cancer.
The new therapy, Yescarta, made by Kite Pharma, was approved for adults with aggressive forms of a blood cancer, non-Hodgkin's lymphoma, who have undergone two regimens of chemotherapy that failed.
The treatment, considered a form of gene therapy, transforms the patient's cells into what researchers call a "living drug" that attacks cancer cells. It is part of the rapidly growing field of immunotherapy, which uses drugs or genetic tinkering to turbocharge the immune system to fight disease. In some cases the treatments have led to long remissions.
"The results are pretty remarkable," said Dr. Frederick L. Locke, a specialist in blood cancers at the Moffitt Cancer Center in Tampa, and a leader of a study of the new treatment. "We're excited. We think there are many patients who may need this therapy."
He added, "These patients don't have other options."
About 3,500 people a year in the United States may be candidates for Yescarta. It is meant to be given once, infused into a vein, and must be manufactured individually for each patient. The cost will be $373,000.
Also at The Associated Press, CNN, and STAT News.
Previously: FDA Approves a Gene Therapy for the First Time
FDA Committee Endorses Gene Therapy for a Form of Childhood Blindness
The Food and Drug Administration (FDA) has approved a gene therapy to treat RPE65-mutation associated retinal dystrophy. But it will be expensive:
A first-of-its-kind gene therapy received approval from the Food and Drug Administration on Tuesday to treat a rare, inherited form of childhood blindness.
The FDA marketing clearance of Spark Therapeutics's Luxturna is historic for scientific and financial reasons. Luxturna is the first gene therapy approved in the U.S. that targets a disease caused by mutations in a specific gene.
A Spark spokesman said the company will not disclose the Luxturna price tag until early January. Wall Street analysts expect the gene therapy to command a $1 million price tag—another first, but not necessarily a welcome one. At a time when drug prices are coming under intense scrutiny, Spark will need to convince insurers, politicians, and pharma critics that the benefit to patients offered by Luxturna justifies its high cost.
Also at NPR.
Previously: FDA Approves a Gene Therapy for the First Time
FDA Committee Endorses Gene Therapy for a Form of Childhood Blindness
The U.S. Food and Drug Administration recently approved a gene therapy for the first time, to treat a form of leukemia. Now an FDA panel has endorsed a gene therapy for an inherited form of blindness. The FDA usually follows the recommendations of its advisory committees:
Gene therapy, which has had a roller-coaster history of high hopes and devastating disappointments, took an important step forward Thursday. A Food and Drug Administration advisory committee endorsed the first gene therapy for an inherited disorder — a rare condition that causes a progressive form of blindness that usually starts in childhood. The recommendation came in a unanimous 16-0 vote after a daylong hearing that included emotional testimonials by doctors, parents of children blinded by the disease and from children and young adults helped by the treatment.
"Before surgery, my vision was dark. It was like sunglasses over my eyes while looking through a little tunnel," 18-year-old Misty Lovelace of Kentucky, told the committee. "I can honestly say my biggest dream came true when I got my sight. I would never give it up for anything. It was truly a miracle." Several young people described being able to ride bicycles, play baseball, see their parents' faces, read, write and venture out of their homes alone at night for the first time. "I've been able to see things that I've never seen before, like stars, fireworks, and even the moon," Christian Guardino, 17, of Long Island, N.Y., told the committee. "I will forever be grateful for receiving gene therapy."
The FDA isn't obligated to follow the recommendations of its advisory committees, but the agency usually does. If the treatment is approved, one concern is cost. Some analysts have speculated it could cost hundreds of thousands of dollars to treat each eye, meaning the cost for each patient could approach $1 million. Spark Therapeutics of Philadelphia, which developed the treatment, hasn't said how much the company would charge. But the company has said it would help patients get access to the treatment.
Despite the likely steep price tag, the panel's endorsement was welcomed by scientists working in the field. "It's one of the most exciting things for our field in recent memory," says Paul Yang, an assistant professor of ophthalmology at the Oregon Health and Science University who wasn't involved in developing or testing the treatment. "This would be the first approved treatment of any sort for this condition and the first approved gene therapy treatment for the eye, in general," Yang says. "So, on multiple fronts, it's a first and ushers in a new era of gene therapy."
Also at MIT.
Previously: Gene Therapy Cure for Sickle-Cell Disease
Gene Therapy to Kill Cancer Moves a Step Closer to Market
In a milestone year, gene therapy is finding a place in medicine
After decades of hope and high promise, this was the year scientists really showed they could doctor DNA to successfully treat diseases. Gene therapies to treat cancer and even pull off the biblical-sounding feat of helping the blind to see were approved by U.S. regulators, establishing gene manipulation as a new mode of medicine.
Almost 20 years ago, a teen's death in a gene experiment put a chill on what had been a field full of outsized expectations. Now, a series of jaw-dropping successes have renewed hopes that some one-time fixes of DNA, the chemical code that governs life, might turn out to be cures. "I am totally willing to use the 'C' word," said the National Institutes of Health's director, Dr. Francis Collins.
[...] The advent of gene editing — a more precise and long-lasting way to do gene therapy — may expand the number and types of diseases that can be treated. In November, California scientists tried editing a gene inside someone's body for the first time using a tool called zinc finger nucleases for a man with a metabolic disease. It's like a cut-and-paste operation to place a new gene in a specific spot. Tests of another editing tool called CRISPR to genetically alter human cells in the lab may start next year. "There are a few times in our lives when science astonishes us. This is one of those times," Dr. Matthew Porteus, a Stanford University gene editing expert, told a Senate panel discussing this technology last month.
Previously: Gene Therapy Cure for Sickle-Cell Disease
Gene Therapy to Kill Cancer Moves a Step Closer to Market
U.S. Human Embryo Editing Study Published
FDA Approves a Gene Therapy for the First Time
Gene Editing Without CRISPR -- Private Equity Raises $127 Million
FDA Committee Endorses Gene Therapy for a Form of Childhood Blindness
FDA Approves Gene Therapy for Non-Hodgkin's Lymphoma
Gene Therapy and Skin Grafting for Junctional Epidermolysis Bullosa
Gene Therapy for Spinal Muscular Atrophy Type 1
Biohackers Disregard FDA Warning on DIY Gene Therapy
CRISPR Used to Epigenetically Treat Diseases in Mice
Gene Therapy Showing Promise for Hemophilia B
Gene Therapy for Retinal Dystrophy Approved by the FDA
CRISPR Treatment for Some Inherited Forms of Lou Gehrig's Disease Tested in Mice
(Score: 0) by Anonymous Coward on Thursday August 31 2017, @12:13PM
ALL
(Score: 2) by Geezer on Thursday August 31 2017, @12:22PM (4 children)
Be nice to see if genetic T-cell modification can be integrated with the nascent 3-D stem cell printing research. It would make for a far more economical, and available treatment than one-off lab cultures.
No, I'm not a biochemist, but I do have a dog in the cancer fight.
(Score: 2) by Joe on Thursday August 31 2017, @01:20PM (2 children)
Stem cells typically dampen-down the immune response, but there have been efforts to use implanted scaffolds to improve CAR T cell therapies for solid tumors (link below).
There are lots of research groups that are trying to generate a one-size-fits-all version that uses donor-derived cells instead of patient-derived cells. Donor-derived would greatly lower costs and improve consistency, but they would also come with a much greater risk of off-target effects (such as a rapid and unstoppable graft-versus-host disease). Kill switches and other genetic modifications will mitigate the risks and improve the efficacy of CAR T cell therapies.
We are in the early days of this type of research and, despite its current success, there is even greater potential for it to be extended to other forms of cancer.
Scaffold: https://soylentnews.org/comments.pl?noupdate=1&sid=19218&page=1&cid=500984#commentwrap [soylentnews.org]
GVHD: https://en.wikipedia.org/wiki/Graft-versus-host_disease [wikipedia.org]
(Score: 2) by Geezer on Thursday August 31 2017, @01:27PM (1 child)
I was just thinking that perhaps CAR T cells are not so different structurally at the cellular from stem cells that the same 3d printing mechanics could be applied, with the resulting reduction in time and cost.
Again, I'm not a bio guy, just a lowly EE, and appreciate better-informed opinion.
(Score: 3, Informative) by Joe on Thursday August 31 2017, @02:02PM
These kind of T cells do not have and would not likely benefit from structural interactions with other cells. One of the great advantages of T cells is that they can "search and destroy" by homing-in on sites of cellular damage and infiltrate densely packed areas to "find" what is responsible and, directly or indirectly, kill it.
T cells already infiltrate tumors and kill cancer cells, but the tumor microenvironment as well as immunoediting can prevent their activity or convert them into a cancer-protecting state (Tregs). The, frankly, amazing success of cancer immunotherapy by blocking immune checkpoints relies on reversing the negative effects of the tumor microenvironment.
https://en.wikipedia.org/wiki/Tumor_microenvironment [wikipedia.org]
https://en.wikipedia.org/wiki/Immunoediting [wikipedia.org]
https://en.wikipedia.org/wiki/Regulatory_T_cell [wikipedia.org]
https://en.wikipedia.org/wiki/Cancer_immunotherapy#Immune_checkpoint_blockade [wikipedia.org]
(Score: 0) by Anonymous Coward on Friday September 01 2017, @03:22PM
Sorry to hear about your dog.
(Score: 2) by fadrian on Thursday August 31 2017, @12:29PM (2 children)
All at the affordable price of ~$450K per treatment.
That is all.
(Score: 2) by sbgen on Thursday August 31 2017, @02:11PM (1 child)
This is an experimental therapy, at the very bleeding edge of the knowledge. Fine-tuning and cost reduction efforts will ensue once it is confirmed to work without much of bad side effects. At the same time the techniques have advanced since the methodology for this therapy was developed so... patience!
Warning: Not a computer expert, but got to use it. Yes, my kind does exist.
(Score: 2) by fishybell on Thursday August 31 2017, @03:42PM
FTFY
(Score: 0, Disagree) by Anonymous Coward on Thursday August 31 2017, @04:20PM (2 children)
We really don't know what the long term effects of these treatments can be. I'm not sure what the best way forward is, but as a species we should be very careful about changing our genetic code. Do these therapies mean that some non-human DNA gets introduced to the population? Or are the gene sequences reliably rewritten to match a healthy human's sequence?
The following is for discussion, I'm not necessarily advocating it: if gene therapy mixes in foreign DNA we may want to sterilize those individuals. They get to live, but after that point cannot possibly contaminate the human gene pool. What if some sequence gets turned on by accident? What if meiosis reorganizes the genes and the addition introduces something harmful? Are we able to reverse changes reliably?
(Score: 4, Informative) by Joe on Thursday August 31 2017, @05:18PM (1 child)
T cells do not undergo meiosis and modifications to them have no plausible mechanisms of spreading into the germ-line. T cells, as well as B cells, are already genetically distinct from the normal genome due to genetic rearrangements and mutations brought about through the actions of RAG proteins.
The modified DNA consists of human-derived sequences that code for a chimeric antigen receptor (CAR) - which is basically an antibody (in this case specific for CD19) fused to part of the cytoplasmic domain of the T cell receptor and other co-stimulatory proteins.
Hypothetically, if such sequences were to be directly introduced into the germ-line, the phenotype of the offspring would likely be similar to Omenn syndrome or other immunodeficiencies.
- Joe
https://en.wikipedia.org/wiki/Meiosis [wikipedia.org]
https://en.wikipedia.org/wiki/Recombination-activating_gene [wikipedia.org]
https://en.wikipedia.org/wiki/Chimeric_antigen_receptor [wikipedia.org]
https://en.wikipedia.org/wiki/Omenn_syndrome [wikipedia.org]
(Score: 0) by Anonymous Coward on Thursday August 31 2017, @07:04PM
Thanks for the details, my comment was more general and I didn't do much checking about this particular therapy. I guess my concerns could be covered by genetic testing, if people are worried about it they can request genetic tests to find out what they'd be exposing their offspring to.