FDA approves second-ever gene therapy for sale in US market

Read Advisory Board's take on this story.

FDA on Wednesday approved Kite Pharma's cell-based gene therapy Yescarta to treat certain adults with aggressive forms of the blood cancer non-Hodgkin lymphoma.

Yescarta, a chimeric antigen receptor (CAR) T cell therapy, is the first approved to treat certain aggressive forms of large B-cell non-Hodgkin lymphoma and the second gene therapy approved for sale in the United States. FDA last month approved the first gene therapy, Novartis' Kymriah, to treat B-cell acute lymphoblastic leukemia in children and adults up to age 25 for whom other treatments did not work. 

How Yescarta works

FDA approved the drug for adults with aggressive forms of non-Hodgkin lymphoma whose condition did not improve or who relapsed after undergoing at least two other chemotherapy regimens. According to the Washington Post's "To Your Health," there about 7,500 individuals in the United States each year who would qualify for being treated with Yescarta.

Each dose of Yescarta involves an individualized process in which a patient's own T-cells are extracted, genetically modified to include a new gene to target and kill lymphoma cells, and infused back into the patient's body. The process transforms a patient's T-cells into a "living drug" to actively attack cancer cells, the New York Times reports.

A clinical trial of 101 adults with refractory or relapsed large B-cell lymphoma who received Yescarta showed the therapy is safe and effective, with a complete remission rate of 51 percent. In addition, cancer tumors shrank in 72 percent of Yescarta users involved in the trial, the Wall Street Journal reports. According to Kite, at six months after receiving Yescarta, 44 percent of patients were still responding to the treatment, with 39 percent having no sign of cancer, "To Your Health" reports.

However, Frederick Locke, an oncologist at Moffitt Cancer Center who co-lead the clinical trial, said roughly 13 percent of patients enrolled in the trial had a life-threatening side-effect called cytokine release syndrome, in which the immune system overreacts to the modified T-cells and causes high fever and flu-like symptoms. Locke said 28 percent of patients experienced neurological "events," such as severe confusion, and three patients died from complications related to the treatment.

As result, FDA said Kite, which recently was acquired by Gilead Sciences, must conduct a post-market observational study to further evaluate Yescarta's long-term safety. In addition, FDA said Yescarta must be sold with a boxed warning label for cytokine release syndrome.

Further, FDA said Yescarta will have a risk evaluation and mitigation strategy (REMS) to ensure the treatment is used safely. For example, FDA will require hospitals and their associated clinics to complete a certification process in order to dispense Yescarta. The certification process will involve training hospital and clinic staff who prescribe, dispense, and administer Yescarta to recognize and manage cytokine release syndrome and nervous system toxicities. As part of the REMS, hospital and clinic staff must inform patients of Yescarta's side effects and the importance of seeking follow-up care if side effects develop.

Yescarta will be introduced into the U.S. market gradually, according to Kite. Kite spokesperson Christine Cassiano said, "10 to 15 authorized institutions will be ready to go at the time of the launch" and in "12 months, [the company] expect[s] to have 70 to 90," because there is "a lot that goes into it, making sure each institution is ready to go."

Pricing

Gilead said it will set the list price for Yescarta in the United States at $373,000—which is lower than Kymriah's list price of $475,000. A Gilead spokesperson said the company set the drug's price based on extensive research with federal agencies that reimburse drug costs, cancer centers, and private insurers. A company spokesperson also cited the clinical trial data, which shows Yescarta works in more patients than the current standard of care. The spokesperson said the price "reflects the value represented by this innovation, and … supports accessibility of this personalized therapy."

Gilead spokesperson Amy Flood said the company is engaged "in ongoing and active discussions with payers" and has "communicated [its] openness to considering different solutions that improve patient access."

Michael Yee, a Jefferies analyst, projected that Yescarta could generate sales of up to $250 million in 2018.

Officials applaud Yescarta's approval

FDA Commissioner Scott Gottlieb said Yescarta's approval "marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases," showing the "continued momentum of this promising new area of medicine," which FDA is "committed to supporting." Gottlieb said FDA "will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine" to clarify that FDA "will apply [its] expedited programs to breakthrough products that use CAR-T cells and other gene therapies."

Peter Marks, director of FDA's Center for Biologics Evaluation and Research, said, "The approval of Yescarta brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options"  (Fiore, MedPage Today, 10/18; Grady, New York Times, 10/18; McGinley, "To Your Health," Washington Post, 10/18; Clarke/Berkrot, Reuters, 10/18; Rockoff,  Wall Street Journal, 10/18; FDA release, 10/18; Gilead Sciences release, 10/18).

Advisory Board's take

Megan Tooley

Deirdre Saulet, Oncology Roundtable

Amid the excitement around these groundbreaking, promising therapies, a major concern rises to the top—cost. Novartis' recently approved CAR T cell therapy, Kymriah, is priced at $475,000 for the procedure alone. Experts estimate that the total cost, including labor and intense symptom management support, could be upwards of $1 million per patient.

While providers may be limited in their ability to bend the cancer drug cost curve, there are ways organizations can better manage their drug spend:

  • Standardize care using clinical pathways that, when appropriate, prompt providers to order lower-cost drugs;
  • Provide education and support to physicians on biosimilars as they come to market; and
  • Help providers and patients understand drug costs, outcomes, and side effects to make informed treatment decisions.

We'll be discussing best practices to help patients on high-cost drug regimens at a webconference on Tuesday, Oct. 24. Register now to secure your spot.

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