With the Food and Drug Administration's Aug. 30 approval of the first-ever gene therapy permitted to enter the U.S. market — Novartis AG's Kymriah — the drug development community has reached a key milestone in delivering on science's promise of transforming clinical medicine, Commissioner Scott Gottlieb said.

Kymriah, also known as tisagenlecleucel, is a chimeric antigen receptor T-cell, or CAR-T, therapy, which are drugs made by taking immune cells from a patient's blood and re-engineering them to attack cancer cells. The cells are then infused back into the person's body.

The FDA approved Kymriah to treat pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, or ALL, the most common type of childhood cancer in the U.S.

Novartis, which has priced its drug at $475,000 for a single course of treatment, has entered into a novel outcomes-based pricing scheme with the Centers for Medicare and Medicaid Services, under which patients will not be charged if they do not respond by the end of the first month following their infusion.

While Kymriah is the first CAR-T medicine approved for the American market, Gottlieb noted there are 76 investigational new drug applications, or INDs, active, meaning the agency has granted its blessing for the products to be studied.

Overall, there are 550 active INDs related to gene therapies, he added.

"Gene therapy products are now being studied in many diseases and conditions, including genetic disorders, autoimmune diseases, heart disease, cancer, diabetes, and HIV/AIDS," Gottlieb told reporters.

"Today is just the first approval in this promising new class of medical products," he said. "Other similar medical opportunities lie just behind this milestone."

Kite Pharma Inc., which is in the midst of an $11.9 billion acquisition by Gilead Sciences Inc., is hoping to be the next to follow Novartis with its own CAR-T drug.

Kite is developing axicabtagene ciloleucel as a treatment for patients with relapsed or refractory aggressive non-Hodgkin lymphoma who are ineligible for autologous stem cell transplant. Kite's application for the CAR-T is under an expedited review by the FDA, which is expected to make a decision by Nov. 29.

The FDA, however, acted a month early on Novartis' application for Kymriah, whose entrance to the market was endorsed in July by a panel of outside cancer experts. So the decision on Kite's product could come sooner than expected, especially given the agency's recent track record of pushing cancer drugs to the market quicker.

Juno Therapeutics is also in the CAR-T race, but its progress was severely slowed after it scrapped its lead product in March after the deaths of five patients from cerebral edema during clinical testing.

A century of science

Gottlieb acknowledged that the path to the first gene therapy approval has been long and not an easy one.

"We've witnessed hardships and even tragedy along the way," he said.

He noted that researchers have spent many decades working on technologies that could modify human cells and tissue using the tools of gene therapy.

"This was always held out as a way to alter the course of many vexing diseases, and maybe even deliver the ability to cure some deadly disorders," Gottlieb said.

Francis Collins, director of the National Institutes of Health, or NIH, said Kymriah's road to the U.S. market actually started more than a century ago, in 1890, when New York-based surgeon William Coley developed a toxin he used to stimulate patients' immune systems to treat their cancer.

"Over the decades, medical interest in immunotherapy waxed and waned; and researchers developed an array of immunotherapeutic interventions, to varying effect," Collins wrote in an Aug. 30 blog.

But the field eventually progressed, making important advances in immunology, cell biology and genetics in the 1970s and 1980s, many of which were supported by the NIH.

The NIH's own Steven Rosenberg, head of tumor immunology at the National Cancer Institute, had some of the early successes in 1980s in what was a precursor to CAR-T therapy — later developing and successfully administering his own version, Collins said.

But it was Carl June and his team of researchers at the Children's Hospital of Pennsylvania in Philadelphia who had turned a major corner in CAR-T research, leading to a collaboration with Novartis on developing Kymriah, he said.

The FDA's approval of Kymriah was driven by the positive results of an open-label, multicenter, single-arm phase II trial, known as ELIANA, in which 83% of the 63 evaluable patients with ALL who received the treatment achieved complete remission or complete remission with incomplete blood count recovery within three months of infusion.

But Collins noted that "many questions must be addressed before we can herald immunotherapeutic approaches to cancer an unqualified success."

"There are still too many severe reactions, too many non-responses or relapses, and, potentially, a very high price tag for their widespread use, which will be truly challenging to scale up," he said. "But we're off to a promising start."