FDA Approves First Cell-Based Gene Therapy for Adults with Relapsed or Refractory Mantle Cell Lymphoma

Rare Daily Staff

The U.S. Food and Drug Administration granted accelerated approval to Tecartus, Gilead subsidiary Kite’s cell-based gene therapy for treatment of adult patients diagnosed with mantle cell lymphoma who have not responded to or who have relapsed following other kinds of treatment.

Tecartus, a chimeric antigen receptor (CAR) T cell therapy, is the first cell-based gene therapy approved by the FDA for the treatment of MCL, and is Kite’s second approved CAR-T therapy.

“Tremendous progress has been made in the discovery of new therapies for debilitating diseases that are difficult to treat. This approval is yet another example of customized treatments that use a patient’s own immune system to help fight cancer, while using a scientific advance in this promising new area of medicine,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. “We’re seeing continued advances in the field of gene therapy and remain committed to supporting innovation in this promising new area of medicine.”

Mantle Cell Lymphoma (MCL) is a rare form of cancerous B-cell non-Hodgkin’s lymphoma that usually occurs in middle-aged or older adults. In patients with MCL, B-cells, a type of white blood cell that help the body fight infection, change into cancer cells that start to form tumors in the lymph nodes and quickly spread to other areas of the body.

Each dose of Tecartus is a customized treatment created using a patient’s own immune system to help fight the lymphoma. The patient’s T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the patient.

The safety and efficacy of Tecartus was established in a multicenter clinical trial of 60 adults with refractory or relapsed MCL who were followed for at least six months after their first objective disease response. The complete remission rate after treatment with Tecartus was 62 percent, with an objective response rate of 87 percent.

Tecartus will be manufactured in Kite’s commercial manufacturing facility in California. In the ZUMA-2 trial, Kite demonstrated a 96 percent manufacturing success rate and a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Manufacturing speed is especially critical for patients with advanced disease, who are very ill and at risk for quick progression.

The label carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and for neurologic toxicities. Both CRS and neurologic toxicities can be life threatening. The most common side effects of Tecartus include serious infections, low blood cell counts and a weakened immune system. Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later.

Because of the risk of CRS and neurological toxicities, Tecartus is being approved with a risk evaluation and mitigation strategy (REMS), which includes elements to assure safe use (ETASU). The risk mitigation measures for Tecartus are identical to those of the current REMS Program for another CAR-T therapy, Yescarta.

To further evaluate the long-term safety of Tecartus, the FDA is also requiring Kite to conduct a post-marketing observational study involving patients treated with Tecartus.

Tecartus was granted Priority Review, and Breakthrough Therapy designations. Tecartus also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.