Treatment 4 min read

FDA Approves First Gene Therapy for Leukemia

Treatment modifies patients’ T cells to fight the blood cancer.

By Kendall K. Morgan featured image The groundbreaking cancer treatment, Kymriah, is customized for each patient. Image courtesy: Novartis

In April 2012, Emily Whitehead became the first pediatric patient ever to receive experimental, genetically modified T cells to treat her life-threatening acute lymphoblastic leukemia (ALL). Three weeks after her treatment, Emily’s cancer had gone into complete remission, and today she’s a happy and healthy 12-year-old. Following many similarly remarkable successes in dozens of other young patients, the Food and Drug Administration recently granted approval to Novartis for the chimeric antigen receptor (CAR) T-cell therapy known as Kymriah (tisagenlecleucel) for children and adults under the age of 26 with advanced and hard-to-treat B-cell precursor ALL.The decision is not only good news for ALL patients; it’s also an important milestone, making Kymriah the first gene therapy ever to gain approval in the U.S. It almost surely won’t be the only such FDA-approved therapy for long. According to Timothy Cripe, a pediatric oncologist at Nationwide Children’s Hospital in Columbus, Ohio, and a member of the FDA’s Oncologic Drugs Advisory Committee, a half dozen or so other CAR-T cell treatments are showing promising results in treating a variety of other blood cancers and could become available in the next year or two.

“This is a ‘Lazarus’ drug; it literally brings back the dead.”

“When you look back and say we treated our first pediatric patient with ALL five and a half years ago, and now we’re at FDA approval — that’s amazing to me,” says Stephan Grupp, the oncologist who led the clinical trial at the Children’s Hospital of Philadelphia and treated Emily. “That’s a very rapid timeline, and it speaks to the compelling results that have been seen with these studies. This is a brand-new kind of treatment. It’s a brand-new way of delivering care, and the drug company had to figure that out, and to see that happen on a global scale is astonishing.”

CAR-T cell therapies are sometimes referred to as “living drugs.” To manufacture the cellular therapy, which is customized for each patient, doctors first collect blood cells and enrich the sample for T cells of the immune system. Those T cells are then modified, using a virus to insert a gene that encodes a particular protein receptor. That protein receptor lends patient T cells a new ability to recognize and kill cancerous cells.

Modified T cells are expanded in the lab and infused back into a patient by the millions. Bruce Levine, who manufactures CAR-T cells for use in clinical trials at Penn Medicine in Philadelphia, says the whole process, including steps to ensure quality and safety, can be completed in less than two weeks.

The recent FDA approval was based on clinical trial results showing that, of 63 children and young adults with ALL who received Kymriah, 83 percent entered remission within three months. Those results were particularly notable given that trial participants had all failed to respond or relapsed following standard ALL treatment. Estimates suggest 15 to 20 percent of the approximately 3,000 young people diagnosed with ALL each year in the U.S. fall into that category and will now be eligible for CAR-T cell treatment.

“This is a ‘Lazarus’ drug; it literally brings back the dead,” Cripe says. “These patients have exhausted all options, and I’ve sat at many of their bedsides with nothing else to offer them, only to later attend their funerals. The fact this new therapy can have such a profound effect on a previously hopeless situation, and with a single infusion, is a true miracle.”

Kymriah can produce severe side effects though. One side effect, cytokine release syndrome (CRS), can result in a potentially life-threatening systemic reaction that includes high fever, flu-like symptoms, and neurological problems. To treat CAR-T cell induced CRS that arises following the infusion of modified cells, the FDA has expanded approval of an immunosuppressive arthritis drug called Actemra (tocilizumab).

Kymriah also comes with a hefty price tag of $475,000. Grupp says there are uncertainties about how insurance companies will respond. However, his team recently sought insurance approval for the very first CAR-T cell patient ever and got it. “Our N of 1 experience is that it worked, but what’s this really going to look like when we do it more routinely?” he asks. “I think everybody will have to figure that out.”

Novartis says that Kymriah will be available to patients at 32 treatment centers around the country specially trained and equipped to deliver the new treatment by the end of the year. And experts expect additional FDA approvals for Kymriah and other CAR-T cell treatments for other blood cancers in the near future. The jury is still out on whether CAR-T cell therapy will find similar success in treating solid cancers — finding the right targets and getting modified T-cells into solid tumors remain major hurdles — but research is underway.

“We all have a really good idea of what we might need to do to extend the CAR-T cell concept to solid tumors and get the T cells actually in the tumor, which is the hard part,” Grupp says. “There’s a lot of innovation going on, and over the next year or two we should start to see clinical trial results that tell us whether that’s going to work.”