FDA advisory committee recommends Novartis' CTL019 for r/r B-cell ALL

Although the FDA is not obliged to follow the recommendations of its advisory panels, it often does so.

Developed by the University of Pennsylvania and Novartis Corp., the therapy could be the first of its kind - an innovative treatment custom-made to target specific forms of cancer, USA Today reports.

"Tisagenlecleucel is an adoptive immunocellular cancer therapy that uses autologous peripheral blood T cells which have been reprogrammed with a transgene encoding a chimeric antigen receptor (CAR) to identify and eliminate CD19-expressing malignant and non-malignant cells", the FDA advisory panel report read.

"This is a major advance", said panel member Dr. Malcolm A. Smith of the National Cancer Institute.

Novartis applied for the approval for its drug, tisagenlecleucel, to treat acute lymphblastic leukemia in children who have exhausted all the existing treatments for the disease. Standard treatments can cure most children, but approximately 15 percent of patients, like Emily, do not respond to treatment or experience relapses.

The treatment would be for children and young adults. It's a concern that stems from the early days of gene therapy, when the genetic tweaking of patient's cells with a modified virus turned on cancer-causing genes. The FDA panel therefore recommended approval for treatment of relapsed or treatment-resistant B-cell acute lymphoblastic leukemia in children and young adults ages 3 to 25.

More than 600 patients in the U.S. each year reach that critical stage.

A handful of other pharmaceutical companies are looking closely at CAR-T as a treatment option for other blood cancers, including a class of cancers known as lymphomas. ALL is the most common childhood cancer in the US.

In drug trials, the immunotherapy results worked far better than chemotherapy and newer types of cancer drugs. A total of 82.5% of the patients went into remission, which is a high rate for the disease. Of the 52 patients examined, 83% had complete remission, although majority suffered serious side effects.

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Instead of having to choose between overpaying to keep KCP or letting him walk, the Pistons move on with his replacement in place. He is widely believed to be the top free agent available in the market, thanks to his youth and two-way style of play.

The main side effect of CTL-019 is cytokine release syndrome, a blistering immune reaction to the drug and the detritus of dying cancer cells.

CTL019 is a customized treatment made by harvesting patients' white blood cells and rewiring them to home in on tumors. At the American Association for the Advancement for Science (AAAS), researcher Stanley Riddell of the Fred Hutchinson Cancer Research Center in Washington, spoke about the miracle treatment that gives cancer patients, who have nothing to lose, hope to gain their lives back.

Novartis staff, working the company's product manufacturing facility in Morris Plains, New Jersey, process T cells before they are shipped back to the patient for infusion. Doctors call it a "living drug" - permanently altered cells that continue to multiply in the body to fight the disease. The whole testing process took 16 weeks on average, which FDA advisers noted could be too long for severely ill patients.

The treatment is also complex and can lead to serious complications, so Novartis plans to initially limit the use of CTL019 to just 30 or 35 approved centers in the United States.

Novartis has confirmed it will file for approval of the cell therapy later this year in the European Union, where it became one of the therapies to enter the EMA's new PRIME expedited approval pathway.

The cost of CAR-T therapy is likely to be hundreds of thousands of dollars, but it's only given once.

Approval of tisagenlecleucel would have implications not only for Novartis, but for companies developing similar treatments, including Kite Pharma Inc, Juno Therapeutics Inc and bluebird bio Inc. Questions also remain about the drug's possible long-term side effects.

The vote also underscores ODAC's ingrained acceptance of moderate risk when it comes to treating patients dying of cancer.

  • Marjorie Miles