Arie Belldegrun, MD
Gilead has announced plans to acquire Kite Pharma, which is the developer of the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19), for $180.00 per share in cash, totaling approximately $11.9 billion. The decision was unanimously approved by both companies and is expected to complete later this year.
The FDA is currently considering a biologics license application for axi-cel for transplant-ineligible patients with relapsed or refractory non-Hodgkin lymphoma (NHL). The application was based on data from the phase II ZUMA-1 study. Under the Prescription Drug User Fee Act (PDUFA), the agency will decide on the axi-cel application by November 29, 2017. Additionally, a marketing authorization application for axi-cel has also been file in Europe.
“From the release of our pivotal data for axi-cel, to our potential approval by the FDA, this is a year of milestones. Each and every accomplishment is a reflection of the talent that is unique to Kite," Arie Belldegrun, MD, chairman, president, and chief executive officer of Kite, said in a statement. "We are excited that Gilead, one of the most innovative companies in the industry, recognized this value and shares our passion for developing cutting-edge and potentially curative therapies for patients.”
In addition to axi-cel, Kite has other CAR T-cell and T-cell receptor (TCR) therapies in development. These will be added to the oncology pipeline held by Gilead, which includes the approved PI3K inhibitor idelalisib (Zydelig). Additionally, the company has a phase III study under way for the MMP3 inhibitor andecaliximab (GS-5745) for patients with gastric cancer.
“The acquisition of Kite establishes Gilead as a leader in cellular therapy and provides a foundation from which to drive continued innovation for people with advanced cancers,” John F. Milligan, PhD, president and chief executive officer of Gilead, said in a statement. “The field of cell therapy has advanced very quickly, to the point where the science and technology have opened a clear path toward a potential cure for patients. We are greatly impressed with the Kite team and what they have accomplished, and share their belief that cell therapy will be the cornerstone of treating cancer.”
In the ZUMA-1 study, a single infusion of axi-cel elicited an objective response rate (ORR) of 82% across patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (TFL), and primary mediastinal B-cell lymphoma (PMBCL). After 8.7 months of follow-up, 44% of patients continued to respond to therapy, including 39% with a complete response (CR).
Those with DLBCL had an ORR of 82% and a CR rate of 49%. After 8.7 months of follow-up, the ORR in the DLBCL group was 36%, which included a CR rate of 31%. In the PMBCL/TFL group, the ORR was 83% and the CR rate was 71%. The 8.7-month ORR rate was 67%, with a CR rate of 63%.
The study included 72 patients with DLBCL and 20 patients with PMBCL or TFL. Axi-cel was successfully manufactured in 110 patients (99%), with an average turnaround time from apheresis to the clinical site of 17 days. The most concerning adverse events with the agent, cytokine release syndrome and neurologic disorders, occurred in 13% and 28% of patients at the primary assessment, respectively.
“CAR T has the potential to become one of the most powerful anti-cancer agents for hematologic cancers," said Belldegrun. "With Gilead’s expertise and support, we hope to fulfill that potential by rapidly accelerating our robust pipeline and next-generation research and manufacturing technologies for the benefit of patients around the world.”
The Kite pipeline also includes other cellular therapies that are advancing into clinical trials. In early August, the company submitted an investigational new drug application for KITE-585, an anti-BCMA CAR T-cell therapy for multiple myeloma. Additionally, the TCR therapies KITE-718 and KITE-439 are also entering clinical development for solid tumors.
For Gilead, the Syk inhibitor entospletinib is in phase II development for patients with hematologic malignancies. Additionally, the BTK inhibitor tirabrutinib is currently being developed for B-cell malignancies.