Gilead Sciences’ Kite subsidiary has won FDA approval for Yescarta™ (axicabtagene ciloleucel), the second time in less than two months that the agency has authorized a chimeric antigen receptor T-cell (CAR-T) treatment for a form of cancer.

As with the first-approved CAR-T therapy, Novartis’ Kymriah (tisagenlecleucel), the FDA acted more than a month ahead of schedule. The agency had set a Prescription Drug User Fee Act (PDUFA) target decision date for Yescarta of November 29, 2017.

The Yescarta approval came 15 days after Gilead completed its approximately $11.9 billion acquisition of Kite (formerly Kite Pharma), a deal announced August 28, two days before Kymriah was approved.

“We believe this is only the beginning for CAR-T therapies,” Arie Belldegrun, M.D., FACS, founder of Kite, said in a statement. “The FDA approval of Yescarta is a landmark for patients with relapsed or refractory large B-cell lymphoma.”

More precisely, Yescarta is the first CAR-T therapy indicated for adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (transformed follicular lymphoma, or TFL).

“This is just the beginning of using cellular therapies in oncology so every new approval is an important step toward the future of care,” Brad Loncar, CEO of Loncar Investments, said in a Twitter tweet yesterday at 5:55 p.m.

Yescarta, formerly KTE-C19, is a CD19-directed, genetically modified autologous T-cell immunotherapy that will be manufactured specifically for each individual patient. Yescarta will be manufactured in Kite’s state-of-the-art commercial manufacturing facility in El Segundo, CA.

Yescarta was approved after a rolling Biologics License Application (BLA) submission completed March 31. Less than two months later on May 26, the FDA granted Yescarta Priority Review—under which the agency set a goal of taking action on Kite’s CAR T-cell candidate within 6 months. The standard review period is 10 months. Yescarta also received the FDA’s Breakthrough Therapy and Orphan Drug designations.

FDA Policy Coming ‘Soon’

“This 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,” FDA Commissioner Scott Gottlieb, M.D., said in an agency statement.

Dr. Gottlieb added that the FDA will “soon” release a comprehensive policy to address how the agency plans to support the development of additional cell-based regenerative medicines: “That policy will also clarify how we will apply our expedited programs to breakthrough products that use CAR-T cells and other gene therapies. We remain committed to supporting the efficient development of safe and effective treatments that leverage these new scientific platforms.”

According to the FDA, DLBCL is the most common type of non-Hodgkin lymphoma (NHL) in adults, representing about one-third of the approximately 72,000 new cases of NHL diagnosed in the U.S. each year.

The FDA based its approval of Yescarta on data from the ZUMA-1 pivotal trial, in which 72% of the 101 patients treated with a single infusion showed an objective response rate to the therapy, with 51% percent of patients showing complete remission.

However, Yescarta was approved with a Risk Evaluation and Mitigation Strategy and will be sold with a Boxed Warning in its product label regarding the risks of cytokine release syndrome (CRS) and neurologic toxicities.

Thirteen percent of ZUMA-1 patients experienced grade 3 or higher CRS, and 31% experienced neurologic toxicities. The most common Grade 3 or higher reactions included febrile neutropenia, fever, CRS, encephalopathy, infections-pathogen unspecified, hypotension, hypoxia, and lung infections. Serious adverse reactions occurred in 52% of patients and included CRS, neurologic toxicity, prolonged cytopenias (including neutropenia, thrombocytopenia and anemia), and serious infections. Fatal cases of CRS and neurologic toxicity occurred.

In ZUMA-1, Kite also showed a 99% manufacturing success rate with a median manufacturing turnaround time of 17 days.

$373,000 List Price

At a list price of $373,000, Yescarta is 21% lower in cost than the first-approved CAR-T therapy, Novartis’ Kymriah (tisagenlecleucel), which was priced at $475,000 when it won FDA authorization on August 30. At the time, Novartis emphasized that it had developed programs to support safe and timely access to the treatment, including support for patients pursuing insurance coverage and financial assistance for uninsured or underinsured patients.

Kite said yesterday it will provide information related to insurance benefits and third-party resources available for travel support for patients through Kite Konnect™, a program focused on providing information and assistance throughout the Yescarta therapy process, including courier tracking for shipments and manufacturing status updates.

A key part of the therapy process, Gilead said, will be assure the safe and effective use of Yescarta for patients and physicians by offering training in administering the immunotherapy. A multidisciplinary field team created this year by Kite to provide education and logistics training will provide final site certification to 16 centers, enabling them to make Yescarta available to appropriate patients.

Kite is actively working to train more than 30 additional centers with an eventual target of 70 to 90 centers across the U.S., Gilead added.

Yescarta remains under regulatory review in Europe, with Gilead anticipating approval in the first half of 2018 following submission of a marketing authorization application in July. As in the U.S, the European Medicines Agency has granted the drug Priority Medicines (PRIME) regulatory support.

“With the combined innovation, talent, and drive of the Kite and Gilead teams, we will rapidly advance cell therapy research and aim to bring new options to patients with many other types of cancer,” added Gilead president and CEO John Milligan, Ph.D.

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