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‘Kymriah’, the new approved treatment for Leukemia

There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory (r/r) B-cell precursor ALL, whose prognosis is poor. Patients often undergo multiple treatments including chemotherapy, radiation, targeted therapy or stem cell transplant, yet less than 10% of patients survive five years.

Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

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. Novartis announced on the 30th of August that the US Food and Drug Administration (FDA) has approved Kymriah(TM)(tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, the first chimeric antigen receptor T cell (CAR-T) therapy, for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes. .The agency considers Kymriah the first gene therapy, it has cleared to hit the market in the United States. 
 
 
The treatment, called Kymriah, aims to give some patients a second chance after first-line drugs have failed. This may happen in up to a fifth of patients, according to the FDA. Kymriah is a novel immunocellular therapy and a one-time treatment that uses a patient’s own T cells to fight cancer
Each dose of Kymriah contains a patient’s own immune cells, which are sent to a lab to be genetically modified using a virus. This therapy — known as chimeric antigen receptor T-cell therapy, or CAR-T — gives the cells the ability to recognize and kill the source of the cancer.
“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,” FDA Commissioner Dr. Scott Gottlieb said in a statement.
Kymriah is an innovative immunocellular therapy that is a one-time treatment. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania (Penn) entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.
“We’ve never seen anything like this before and I believe this therapy may become the new standard of care for this patient population,” said Dr. Stephan Grupp, director of cancer immunotherapy at Children’s Hospital of Philadelphia, which spearheaded this research.
An FDA advisory committee had recommended the therapy for approval in July to treat the relapse of a blood cancer known as B-cell acute lymphoblastic leukemia, or ALL.  FDA,  is 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 ther nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Based on available data, patients on the treatment have had an 89% chance of surviving at least six months and a 79% chance of surviving at least a year, with most being relapse-free at that point.
Almost 5,000 people were diagnosed with ALL in 2014, according to the US Centers for Disease Control and Prevention. More than half were children and teens. ALL is the most common type of cancer among children, according to the National Cancer Institute.
Most patients with ALL recover through other treatments such as radiation, chemotherapy and stem cells. But if the cancer recurs, the prognosis is poor.
“There has been an urgent need for novel treatment options that improve outcomes for patients with relapsed or refractory B-cell precursor ALL,” Novartis, the drug company that makes Kymriah, said in a statement.
“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.
The one-time treatment has a boxed warning for cytokine release syndrome or CRS, a life-threatening side effect that can cause blood pressure to drop dangerously low. It is caused by overactive genetically modified immune cells. The FDA said hospitals and clinics must become certified to distribute the treatment, meaning they are prepared to recognize and treat CRS and other potentially fatal neurological events. Novartis said it hopes to have an initial network of 20 treatment centers within a month with plans to expand that to 32 by the end of the year.
Price of Kymriah
Kymriah has a $475,000 price tag; however, patients who do not respond within a month of treatment will not be charged, according to Novartis.
“Novartis is collaborating with (Centers for Medicaid Services) to make an outcomes-based approach available to allow for payment only when pediatric and young adult ALL patients respond to Kymriah by the end of the first month. Future potential indications would be reviewed for the most relevant outcomes-based approach,” the drug company said in a statement.
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The FDA also expanded approval for another drug, tocilizumab, to treat CRS in patients 2 and older.
In the main study that informed the advisory committee’s decision in July, roughly half of 68 patients experienced high-grade CRS, though none died from it. Slightly fewer patients experienced neurological events, such as seizures and hallucinations.
Novartis is required to conduct followup study to assess the safety of the treatment long-term.

Emily Whitehead, shown with her parents, Thomas and Kari Whitehead, was the first child treated with a new type of cancer therapy that uses the patient’s own genetically modified cells to fight cancer. (Sean Simmers for The Washington Post)
 

 

 


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