text: The U.S. Food and Drug Administration today approved Yescarta (axicabtagene ciloleucel), a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. Yescarta, a chimeric antigen receptor (CAR) T cell therapy, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL). 
   
   “Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer,” said FDA Commissioner Scott Gottlieb, M.D. “This approval demonstrates the continued momentum of this promising new area of medicine and we’re committed to supporting and helping expedite the development of these products. We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine. That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.” 
   
   Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL in adults. NHLs are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and DLBCL represents approximately one in three newly diagnosed cases. Yescarta is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. 
   
   Each dose of Yescarta is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T-cells, a type of white blood cell, are collected and genetically modified to include a new gene that targets and kills the lymphoma cells. Once the cells are modified, they are infused back into the patient. 
   
   “The approval of Yescarta brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options – those adults with certain types of lymphoma that have not responded to previous treatments,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). 
   
   The safety and efficacy of Yescarta were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Yescarta was 51 percent. 
   
   Treatment with Yescarta has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Other side effects include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment with Yescarta usually appear within the first one to two weeks, but some side effects may occur later. 
   
   Because of the risk of CRS and neurologic toxicities, Yescarta is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The FDA is requiring that hospitals and their associated clinics that dispense Yescarta be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Yescarta are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop. 
   
   To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Yescarta. 
   
   The FDA granted Yescarta Priority Review and Breakthrough Therapy designations. Yescarta also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The Yescarta application was reviewed using a coordinated, cross-agency approach. The clinical review was conducted by the FDA's Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination. 
   
   The FDA granted approval of Yescarta to Kite Pharma, Inc. 
   
   The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines, and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. 
   
   ### ||||| In 2010, Josh Feldman was on his honeymoon -- a globe-spanning trip that at one point involved swimming with humpback whales -- when he noticed a "Garbanzo-sized" lump on the back of his neck. It turned out to be lymphoma, which worsened even as he cycled through treatments: chemotherapy, the immunotherapy Opdivo, a targeted drug called Zydelig. What actually worked for the 55-year-old photographer was a radical treatment in which his own white blood cells were genetically re-engineered to kill his cancer. Compared to the other drugs, it was "a walk in the park," he said earlier this year while overlooking a mango tree on his property. "I'd like to see it become first-line therapy," he said. In September, 15 months after his treatment, he was still in remission. 
   
   That's still a long way away. But the treatment Feldman received was just approved by the Food and Drug Administration under the brand name Yescarta, with a bracing price tag: $373,000 per patient. That doesn't include the costs of dealing Yescarta's side effects, which include life-threatening fevers triggered by the immune response the therapy creates that can mean weeks in the hospital, or other drugs patients must receive. 
   
   FDA Commissioner Scott Gottlieb, himself a cancer survivor, called Yescarta "another milestone in the development of a whole new scientific paradigm." David Maloney, a physician at the Fred Hutchinson Cancer Research Center, had this to say about Yescarta's approval in a prepared statement: "There will likely be thousands of lives saved in the next few years because of it." Louis DeGennaro, the chief executive of the Leukemia and Lymphoma Society, which helped fund Yescarta's development, wrote in an email blast that "many patients who were out of treatment options are now in remission" because of experimental studies of the drug. 
   
   It's no surprise that the excitement comes at a high economic price. In August, the treatment's developer, Kite Pharmaceuticals, was purchased by biotech giant Gilead Pharmaceuticals for $11.9 billion, a price which made Kite founder and chief executive Arie Belldegrun's shares worth some $600 million. The process of making the drug is laborious and expensive. But critics are likely to counter that much of the work of developing the drug was done by the National Cancer Institute, by Steven Rosenberg, a researcher there. 
   
   Yescarta is the second treatment of its kind, called a Chimeric Antigen Receptor T-Cell, or CAR-T, for the particular genetic modifications made to white cells. The first, Kymriah, for Novartis, was addressed at children with acute lymphoblastic leukemia, a small group of patients. Yescarta is being approved for a much larger population. About 24,000 Americans are diagnosed with diffuse large-cell b-cell lymphoma (DLBCL), the variety Yescarta treats, every year. 
   
   Novartis priced Kymriah at $475,000, which makes Kite's price sound significantly lower. But Novartis said it is offering insurance companies a unique, "value-based" pricing structure, in which it only pays for those patients who go into remission withing three months. For Novartis' treatment in DLBCL, that's only 45% of patients, which means at the $475,000 price, Novartis would only be receiving about $200,000 per patient. (Novartis has not said how it will price in DLBCL). 
   
   In patients' whose disease did not shrink after chemotherapy, Yescarta shrank tumors 70% of the time. More impressively, 51% went into complete remission, meaning their cancer was undetectable. The severe fever and neurological side effects led the FDA to give the treatment a boxed warning, its most severe. 
   
   Kite also boasts about its ability to manufacture individual CAR-T cells for each patient. "Our manufacturing success rate was 99% and the turnaround had a median of 17 days," said David Chang, Kite's chief scientific officer. "I haven’t anything close to that coming from Novartis." 
   
   In an interview conducted before the approval, Chang also had a response for critics who point to the role that the NCI and the Leukemia and Lymphoma Society had in developing Yescarta as an argument that it should cost less. He says that people don't have enough appreciation of the difficult of moving from government-sponsored research to an approved, manufactured product. 
   
   "Look," Chang said, "Government is not in the business of making and commercializing a drug. They are more in the business of creating the innovation. And innovation has to be matched with the right private company to make sure all the right necessary steps are done. This is the underlying premise of how the credo is set. Both for the government the private sector and ultimately for the patients." 
   
   Chang says Kite (now Gilead) is developing CAR-T treatments for other cancers. It will test a CAR-T against a target called BCMA in multiple myeloma, another targeted against cancers caused by the human papilloma virus, and a third against MAGE3, hoping to to move the technology beyond cancers of the blood. "The clinical results are really, really different from anything else that proceeded that before," Chang said.
target: – The Food and Drug Administration has approved a second "living drug" to fight cancer—a personalized treatment that alters a patient's own cells to turn them into cancer-killers. The new "CAR T-cell therapy" has been approved for non-Hodkins lymphoma patients with few other treatment options, a group that could number around 3,500 per year, the Washington Post reports. But the innovative therapy won't come cheap: Forbes reports that the cost will be $373,000 per patient, not including the cost of treating side effects that could include dangerous fevers. A similar treatment approved for leukemia in July costs $475,000 per patient. Doctors believe the new treatment, produced by Kite Pharma under the brand name Yescarta, could save thousands of lives, the New York Times reports. In the study that led to FDA approval, 54% of 101 patients went into complete remission, and 39% of the 101 were still in remission an average of 8.7 months later. "Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases," FDA Commissioner Scott Gottlieb said in a statement. "In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer." (The fight against breast cancer is also making progress.)