FDA most likely to approve first gene therapy drug


Advisory committee for the first time recommended a gene therapy drug for approval to the US Food and Drug Administration. This will be the first gene therapy to hit the market, if approved. This drug could provide a second chance to patients suffering from leukemia, whose first-line drugs have failed.

A bunch of experts voted to endorse the tisagenlecleucel, the immunothetapy drug which treats a type of leukeima that is more common among children. In the committee there war no votes against, ten were in favor and one did not vote. This drug gives ability to the patients’ immune cells to identify and kill the source of cancer.

Dr. Catherine Diefenbach, clinical director of lymphoma at the NYU Perlmutter Cancer Center called discovering of this drug “astounding” and said, “Which one wins is really the question of life or death,” regarding its method of battling with the cancer.

The research that was presented to the committee examined the drug as the way of treatment for the relapse of a blood cancer called B-cell acute lymphoblastic leukemia, or just ALL. According to National Cancer Institute, this type is the most common among children.

According to the US Centers for Disease Control and Prevention in 2014, about 5000 people were diagnosed with acute lymphoblastic leukemia. Teens and children represented around 14 percent the ones who died that same year.

Most common recovering treatments for ALL are chemo, radiation and stem-cell transplantation. And it works for vast majority of patients, but if the disease comes back, the results can be critical.

Dr. Stephan Grupp, director of the Cancer Immunotherapy Program at Children’s Hospital of Pennsylvania, said, “The patients who are left behind when chemotherapy doesn’t work are left in really tough shape.” His clinic participated in this research.

This drug also has some fatal side effects. One of them is cytokine release syndrome or CRS, which causes blood pressure to drop critically low, it “looks like sepsis”, said Diefenbach. She also added this would restrict using this drugs only in those hospitals that are equipped to deal with this complication. Although nobody died, about half of 68 patients that were receiving the drug experienced high-grade CRS. Some smaller number of patients expirienced nerulogical side effects, such as hallucinations and seizures

Also patients are likely to come down with some infections, as the treatment kills certain type of immune cells. According to the brief documents, three patients died with various infections about three months after drug’s infusion.

But positive side, including the lack of other options and overall effectiveness probably persuaded the committee. Data say that patients had an 89% chance of surviving at least six months and a 79% chance of surviving one year or more, with the majority being relapse-free at that point.

“They’re taking some people that had incurable diseases and potentially turning them into curable diseases,” said Dr. Joshua Brody, director of the Lymphoma Immunotherapy Program at Mount Sinai’s Icahn School of Medicine.
Tisagenlecleucel is a type of immunotherapy called chimeric antigen receptor T-cell therapy, or CAR-T. These drugs are made by removing immune cells from a patient, genetically modifying them using a virus and putting them back into the patient. The virus creates a new cell receptor that targets another receptor on the cancer cells: CD19. This modification is causing the cells to attack the cancer cells.

In theory, this method could induce other cancers, as it is modifying immune cell DNA. But there were no cases of this happening with the CAR-T treatment for now. “We’ve never seen this theoretical thing,” Brody said, adding that the chance of any adverse event happening is certainly smaller than the certain death of relapsed cancer. “It’s not an opinion. This is straightforward numbers.”

Brody said that immunotherapy treatments of this kind need the usage of patients’ own immune cells, as they would “almost never (find) a match” in an off-the-shelf product. “You can put someone else’s red blood cells into you,” he said. “You can almost never put someone’s (immune) cells into you.”

Dr. John Maris, a pediatric oncologist at The Children’s Hospital of Philadelphia and leader of the SU2C-St. Baldrick’s Pediatric Cancer Dream Team said, “This therapy will no doubt save the lives of many children and young adults who have had no other effective therapy,” adding that “This is truly a turning point in the management of this disease.”

Amgen’s blinatumomab is another drug that treats ALL, but “it’s overall not quite as good” as the data from the Novartis trials.

Although FDA is classifying Novartis drug as gene therapy, it refer to the drug as immunotherapy.

Novartis did not want to say anything on the drug’s price tag, it only said it expects the FDA to decide by October.