The FDA has approved axicabtagene ciloleucel, a cell-based gene therapy, to treat adult patients with certain types of large B-cell lymphoma who have not responded to or who have relapsed after at least two other kinds of treatment. A CAR-T cell therapy, axicabtagene ciloleucel, is the second gene therapy approved by the FDA and the first for certain types of non-Hodgkin lymphoma (NHL).
"Today marks another milestone in the development of a whole new scientific paradigm for the treatment of serious diseases. 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," said FDA Commissioner Scott Gottlieb, MD. "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.
"We will soon release a comprehensive policy to address how we plan to support the development of cell-based regenerative medicine," he continued. "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."
Approximately 72,000 new cases of NHL are diagnosed in the U.S. each year, and diffuse large B-cell lymphoma (DLBCL) represents approximately one in three newly diagnosed cases. Axicabtagene ciloleucel is approved for use in adult patients with large B-cell lymphoma after at least two other kinds of treatment failed, including DLBCL, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. The treatment is not indicated for the treatment of patients with primary central nervous system lymphoma.
"The approval of [axicabtagene ciloleucel] brings this innovative class of CAR-T cell therapies to an additional group of cancer patients with few other options – those adults with certain types of lymphoma that have not responded to previous treatments," said Peter Marks, MD, PhD, Director of the FDA's Center for Biologics Evaluation and Research (CBER).
The safety and efficacy of axicabtagene ciloleucel were established in a multicenter clinical trial of more than 100 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment was 51 percent.
Treatment with axicabtagene ciloleucel has the potential to cause severe side effects. It carries a boxed warning for cytokine release syndrome (CRS) and for neurologic toxicities. Both CRS and neurologic toxicities can be fatal or life-threatening. Other side effects include serious infections, low blood cell counts, and a weakened immune system. Side effects from treatment with axicabtagene ciloleucel usually appear within the first 1-2 weeks, but some side effects may occur later.
Because of the risk of CRS and neurologic toxicities, axicabtagene ciloleucel is being approved with a risk evaluation and mitigation strategy, which includes elements to assure safe use. The FDA is requiring that hospitals and their associated clinics that dispense axicabtagene ciloleucel be specially certified. As part of that certification, staff involved in the prescribing, dispensing, or administering of the therapy are required to be trained to recognize and manage CRS and nervous system toxicities. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop.
To further evaluate the long-term safety, the FDA is also requiring a post-marketing observational study involving patients treated with axicabtagene ciloleucel.
The FDA granted axicabtagene ciloleucel Priority Review and Breakthrough Therapy designations. The treatment also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.