FDA Approves Gilead/Kite's Yescarta as First CAR-T for Follicular Lymphoma

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The U.S. Food and Drug Administration (FDA) approved Gilead and Kite’s Yescarta (axicabtagene ciloleucel) for adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This makes Yescarta the first chimeric antigen receptor (CAR) T-cell therapy approved for patients with indolent FL. It was under Accelerated Approval.

FL is a type of indolent non-Hodgkin lymphoma (iNHL) where malignant tumors grow slowly but can become more aggressive. It is the most common form of indolent lymphoma and the second most common type of lymphoma around the world, making up about 22% of all lymphomas diagnosed.

The approval was based on data from ZUMA-5, a single-arm, open-label trial where 91% of patients with r/r FL responded to the treatment, including an estimated 74% of them in continued remission at 18 months. Of all the FL patients, median duration of response was not hit at a median follow-up of 14.5 months.

In terms of safety, Grade 3 or higher cytokine release syndrome was observed in 8% of patients and neurologic toxicities in 21% of patients. The therapy comes with a Boxed Warning for risks of cytokine release syndrome and neurologic toxicities. It is approved with a risk evaluation and mitigation strategy (REMS), as a result, which requires institutions approved to provide the treatment to under specializing training and protocols.

“Once a follicular lymphoma patient’s disease relapses, the duration of response to care shortens with each round of therapy,” said Caron A. Jacobson, Medical Director, Immune Effector Cell Therapy Program, Dana-Farber Cancer Institute and Assistant Professor of Medicine, Harvard Medical School. “Additionally, for follicular patients in the third line of therapy, the five-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission.”

Jacobson added, “Impressively, 91% of follicular lymphoma patients in the ZUMA-5 study responded to a single infusion of axicabtagene ciloleucel, including an estimated 75% of patients in a continued remission at 18 months, giving these patients much-needed hope and oncologists an important addition to the treatment armamentarium.”

Christi Shaw, chief executive officer of Kite, stated, “As we look to bring the hope of survival to more patients in need, today’s FDA decision represents a real step forward in our commitment in hematologic malignancies. Advancing CAR T therapies for patients across lymphomas remains a cornerstone of our cell therapy development program, and we are excited about the potential of Yescarta for patients with indolent follicular lymphoma.”

Gilead also announced today new, long-term data from its open-label extension (OLE) trial of two Phase III studies (Study 1489 and Study 1490) of Biktarvy. The data demonstrated the efficacy and safe of the drug for the treatment of HIV-1 in treatment-naïve adults, with no treatment-emergent resistance. The company presented the data at the 28th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2021).

In both trials, more than 98% of participants who started treatment with Biktarvy and stayed in the study achieved and held an undetectable viral load, defined as less than 50 copies per milliliter, through four years of follow-up. This high efficacy and viral suppression were also seen in patients who switched to Biktarvy from a dolutegravir-containing triple therapy for the 48-week OLE periods.

“Gilead is committed to developing innovative HIV treatments, like Biktarvy, that help to address the unmet needs of people living with HIV today, including achieving and maintaining an undetectable viral load over the long-term,” said Diana Brainard, senior vice president, Virology Therapeutic Area, Gilead. “These data reinforce that Biktarvy provides durable viral suppression, strong efficacy and a high barrier to resistance in both adults that are new to HIV therapy and those replacing their existing treatment.”

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