‘Astounding’ second-chance cancer drug heading for FDA approval
A new gene therapy drug, the first of its kind, was recommended for the approval of the US Food and Drug Administration by an advisory committee Wednesday. If approved by the FDA, the agency considers this to be the first gene therapy to hit the market.
The drug may provide a second chance for some leukemia patients whose first-line drugs have failed.
A panel of experts voted to approve the anti-immunotherapy drug, known as tisagenlecleucel, which treats a more common type of leukemia in children. Ten members voted in favor, and one left before the vote begins. None voted against.
The drug allows the immune cells of patients to recognize and destroy the source of the cancer: a different immune cell disappeared.
“This victory is really the issue of life and death,” said Catherine Diefenbach, clinical director of the NYU Perlmutter Lymphoma Cancer Center.
Diefenbach, who was not involved in drug research and has no connection to its manufacturer, Novartis, described the results as “astounding.”
The research presented to the committee studied the drug as a treatment for the relapse of blood cancer known as acute lymphoblastic leukemia B or ALL cells. This is the most common type of cancer in children, according to the National Cancer Institute.
About 5,000 people were diagnosed with acute lymphoblastic leukemia in 2014, the most recent year on record, according to the Centers for Disease Control and Prevention. Although more than half of the people with this diagnosis were children and adolescents, they only accounted for 14% of those who died that year.
The vast majority of people with ALL recover with other treatments, such as chemotherapy, radiation therapy and stem cell transplantation. But if the cancer returns, the prognosis can be severe.
“Patients who are left behind when chemotherapy does not work are left in a very difficult way,” said Dr. Stephan Grupp, director of the cancer immunotherapy program at the Children’s Hospital of Pennsylvania during the FDA Advisory Committee meeting.
His hospital is one of the 26 clinical centers that participated in the study, and served as principal investigator there. As such, he studied and treated tisagenlecleucel patients for more than five years and receives research support from Novartis.
However, the drug has side effects that can be fatal, such as cytokines or CRS release syndrome, which “looks like sepsis” and leads to a drop in blood pressure, said Diefenbach. This could limit the availability of the drug to hospitals that are specially equipped to deal with this complication, he added.
In this critical study informed the committee’s decision, about half of the 68 patients who received the drug experienced a higher BCC, although there were none.
Slightly fewer patients had neurological side effects such as seizures and hallucinations, according to the committee’s backgrounder.
And because the treatment kills a type of immune cell, patients are more likely to fall with certain infections. At least three patients died with various fungal infections – including viruses, bacteria and – more than a month after the one-time infusion of the drug, according to the report.
However, overall drug efficacy and lack of other options seem to have won the committee: About 89% of patients in the small trial survived at least six months and 79% survived at least one year. Most were also relapsed in the same period.
“They take people who INEXPUGNABLE diseases and potentially make them curable diseases,” said Dr. Joshua Brody, director of the Lymphoma Immunotherapy Program at Mount Sinai Icahn Medical School. Brody helped design trials for similar drugs, but not for Novartis.
Tisagenlecleucel is a type of immunotherapy called chimeric antigen receptor T-cell therapy, or CAR-T.