FDA Approves Iovance Biotherapeutics’ Lifileucel as First Cell Therapy for Solid Tumors
The U.S. Food and Drug Administration (FDA) has granted approval to Iovance Biotherapeutics’ lifileucel, making it the first one-time cell therapy for solid tumors and the first tumor-infiltrating lymphocytes (TIL) therapy. The approval was granted under the FDA’s Accelerated Approval pathway, which allows the approval of medicines for serious or life-threatening diseases based on surrogate endpoints that predict clinical benefit.
The approval of lifileucel, known commercially as Amtagvi, is a significant milestone in the field of TIL therapy. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, stated that the approval represents the culmination of scientific and clinical research efforts, offering a novel T cell immunotherapy for patients with limited treatment options.
Melanoma, a type of skin cancer, claims the lives of approximately 8,000 people in the U.S. each year. The approval of Amtagvi provides hope for those with advanced melanoma who have not responded to standard therapies. Samantha R. Guild, president of AIM at Melanoma Foundation, expressed optimism about the approval, stating that current treatment options are ineffective for many patients.
Amtagvi is approved for autologous use only, meaning it uses a patient’s own immune cells. However, it carries a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment.
TIL technology has been in development for nearly four decades. Developed by Steven Rosenberg and colleagues at the National Cancer Institute in 1982, TIL therapies take advantage of the patient’s own immune cells, which can be extracted from tumor biopsies, expanded in numbers or enhanced for better efficacy, and then transfused back into the patient. This process leads to antitumor activity.
TIL therapies have an advantage over CAR-T therapies when it comes to treating solid tumors. While CAR-T therapies have revolutionized the treatment of blood cancers, they face challenges when used against solid tumors. TILs have the ability to recognize multiple antigens simultaneously, making them more effective in treating solid tumors, which are known to be heterogeneous.
Iovance is the first company to receive FDA approval for a TIL therapy against advanced melanoma. The approval is a significant breakthrough, as there are currently no FDA-approved options for advanced melanoma after standard treatments. Lifileucel has shown promising results in clinical trials, with a 31% objective response rate and a median duration of response not yet reached at 18.6 months follow-up.
While the approval is a major achievement, there are challenges in scaling up manufacturing. TIL production time typically takes four to six weeks, and patient-to-patient variation is a significant challenge in scaling manufacturing. Until these challenges are resolved, the cost of TIL therapies is expected to remain high.
Iovance, however, is confident in its manufacturing capabilities. The company has shortened the manufacturing time for lifileucel from six weeks to 22 days and has established a centralized cell therapy center in Philadelphia to meet potential demand.
In addition to melanoma, Iovance is exploring the potential of TIL therapy in other solid tumor types, including metastatic non-small cell lung cancer (NSCLC) and gynecological cancers. Other companies, such as Lyell and Obsidian Therapeutics, are also developing TIL therapies for various indications.
The approval of lifileucel is expected to usher in a new wave of innovation in the treatment of all solid tumors. TIL therapy has the potential to offer long-term curative responses for patients and could have broader implications in the treatment of many other cancer types.
The approval of Iovance Biotherapeutics’ lifileucel marks a significant milestone in the field of TIL therapy. With its potential to redefine the treatment paradigm for patients with advanced melanoma, lifileucel offers hope to those who have exhausted standard treatment options. As companies continue to develop TIL therapies for various indications, the approval is expected to drive further innovation in the treatment of solid tumors.