- Gilead Sciences Inc. on Wednesday secured U.S. approval for its newly acquired CAR-T therapy, giving adult patients with a certain type of lymphoma and few other options a promising new treatment that offers the hope of remission for some.
- The regulatory OK, while expected, puts Gilead at the forefront of cancer cell therapy development and validates the biotech's decision to buy the drug's original developer, Kite Pharma Inc., for $11.9 billion in August.
- Gilead will market the therapy under the brand name Yescarta at an annual cost of $373,000 — a price that underscores the affordability challenges presented by the personalized nature of CAR-T treatment. Although the amount is less than the $475,000 that Novartis AG charges for its CAR-T therapy Kymriah, Gilead's drug treats a different and more prevalent form of blood cancer.
"We believe this is only the beginning for CAR-T therapies," said Kite founder Arie Belldegrun in a statement on the approval. Under Belldegrun's leadership, Kite rapidly advanced the clinical science of CAR-T, navigating the safety challenges characteristic of the treatment and establishing leadership in a space that many now see as a major advance in how certain cancers are treated.
Throughout the development of Yescarta (axicabtagene ciloleucel), Kite stayed neck and neck with the larger and well-resourced Novartis AG. While Novartis can claim the landmark of winning the first ever approval of a CAR-T therapy, Gilead's near $12 billion takeover of Kite is a worthy second prize.
That two CAR-T therapies are now on the market is a testament to the steady progress in gene modification technology and its applications for cell therapy. In CAR-T, patient T-cells are extracted and genetically engineered to express what's known as a chimeric antigen receptor or CAR. These modified T-cells are then reinfused back into the patient, where they target a protein typically expressed on the surface of B-cell cancers.
"In just several decades, gene therapy has gone from being a promising concept to a practical solution to deadly and largely untreatable forms of cancer," wrote Scott Gottlieb, Commissioner of the Food and Drug Administration, in a Oct. 18 statement. "The approval demonstrates the continued momentum of this promising new area of medicine and we’re committed to supporting and helping expedite the development of these products."
The FDA approved Yescarta for treatment of adult patients with relapsed or refractory large B-cell lymphoma who have previously received two or more lines of systemic treatment. The therapy's label will include diffuse large-B cell lymphoma (DLBCL) as well as several other B-cell lymphoma types.
In this regard, Yescarta is approved to treat a broader group of patients than Novartis' Kymriah (tisagenlecleucel), which was OK'd for use in children and young adults with twice-relapsed acute lymphoblastic leukemia (ALL).
Kite estimates about 7,500 patients each year will be eligible for Yescarta, compared to the only 600 or so patients Novartis estimates Kymriah's label currently covers.
Yescarta will cost $373,000 a year, a price that could strain insurers' willingness to pay and will likely invite criticism. When Yescarta works, patients who have failed other therapies and face extremely poor outcomes have seen remarkable remissions. While most patients respond initially, however, a good number eventually see their cancer return — raising questions about value for a pricey treatment designed to be single use.
In Yescarta's pivotal clinical trial, a study known as ZUMA-1, treatment led to complete responses in 36% of the just-over 100 patients included in the study. At a median follow-up of 8.7 months in the primary analysis, more than half of patients were still alive.
But CAR-T also comes with significant side effects, most commonly a severe immune response known as cytokine release syndrome (CRS) as well as neurotoxicity. In ZUMA-1, 13% of patients experienced Grade 3 or higher CRS and 31% had some type of neurological toxicity. Yescarta will carry a black box warning, the FDA's strictest, for these two side effects and will only be available through a Risk Evaluation and Mitigation Strategy program.
In part to address some of the concerns around CAR-T, Novartis said it would collaborate with the U.S. government to allow for payment only if patients respond to treatment with Kymriah by the end of the first month. Gilead and Kite haven't announced any plans for a similar arrangement, which could invite more scrutiny of the Yescarta's value.
The Swiss pharma also indicated it could price the treatment lower for indications other than the narrow slice of ALL patients it is currently approved to treat. Kymriah has also been studied in DLBCL and Novartis plans to file for approval in a similar indication to Yescarta's by the end of the year. If Kymriah is approved in that indication, the comparable prices of the two CAR-T therapies could end up similar.
For Gilead, approval of Yescarta will give it a premier cancer asset when sales of its mainstay hepatitis C products are falling. To be sure, even an excellent commercial launch would fall short of replacing those lost revenues. But Yescarta — and Kite's other programs in development — mean Gilead is instantly a player in one of the most exciting fields of oncology.