Although only three gene therapies have been approved in the United States—all in 2017—these innovative treatments are leaving their imprint on the healthcare system.
Novartis’ Kymriah (tisagenlecleucel), a chimeric antigen receptor (CAR)T-cell therapy for certain pediatric and young adults with a form of acute lymphoblastic leukemia received a nod last August, and Kite’s Yescarta (axicabtagene ciloleucel), a CAR T-cell therapy for non-Hodgkin lymphoma, in October.
Spark Therapeutics’ Luxturna (voretigene neparvovec-rzyl) for retinal dystrophy, approved in December, is the first gene therapy in the U.S. to be administered directly, delivering a normal copy of the RPE65 gene into retinal cells.
Price tags for these therapies are unprecedented but hardly unexpected. Luxturna sells for $850,000 per course of treatment, Kymriah for $475,000 per course, and Yescarta for $373,000 per course.
Other targeted areas ripe for gene therapy are hemophilia, immune deficiency, and sickle cell anemia, and all are in clinical trials. Strimvelis, which treats a rare immune system disorder called ADA-SCID, or “bubble boy” syndrome, has been approved in Europe but not in the U.S.
How it works
Gene therapy, which restores an abnormal or mutated gene but does not remove or modify defective DNA, introduces genetic material into cells via a carrier called a vector. Vectors are usually viruses that can infect a cell but won’t cause disease. The two primary types of viruses are retroviruses that integrate their genetic material into a chromosome for replication and adenoviruses that enter a cell’s nucleus, the latter most commonly used in cancer treatment.
DNA is injected or given intravenously directly into a specific tissue (in vivo), or cells can be removed, treated in a lab setting, and returned to a patient to make a functioning protein (en vivo). The latter method is used for Kymriah, in which T-cells are genetically modified to contain a protein that targets and kills leukemia cells.
Genome editing, which can facilitate gene therapy, allows DNA to be inserted, deleted, modified, or replaced in a human cell to correct defective DNA. In essence, editing can eliminate problems in DNA and remove deadly inherited diseases. CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats) is the gene editing technology du jour, in which a Cas9 protein performs like molecular scissors, cutting strands of DNA and shutting off the targeted gene.
“Gene editing has tremendous promise; it can fight back against cancer by making cells resistant,” says Ben Solomon, managing director, GeneDx, a genetic testing company.
Thus far in the United States, CRISPR has not successfully fixed a genetic defect in a human patient, but has in human embryos with a mutation that can cause serious heart problems. China is far ahead of the U.S. in deploying the technology with fewer regulatory barriers and has already genetically engineered at least 86 cancer and HIV patients, according to an article in the Wall Street Journal in January 2018. The University of Pennsylvania is awaiting federal clearance to move ahead with the technology.