Amtagvi Approved to Treat Melanoma

On Feb. 16, 2024, the U.S. Food and Drug Administration (FDA) granted Accelerated Approval for Amtagvi^™ (lifileucel – Iovance Biotherapeutics). It is a tumor-infiltrating lymphocyte (TIL) cell therapy that treats adults who have melanoma that cannot be removed surgically or that has spread. The first cell therapy for a solid cancer will be used after other treatments have failed. Patients will receive one intravenous (IV) infusion at a wholesale acquisition cost (WAC) of $515,000.  Complete prescribing information for Amtagvi is here.

At a Glance

• Brand (Generic) Name: Amtagvi (lifileucel)
• Manufacturer: Iovance Biotherapeutics
• Date Approved: Feb. 16, 2024
• Indication: to treat adults who have unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor
• Dosage Forms Available: a single IV infusion containing 7.5 x 10⁹ to 72 x 10⁹ viable cells
• Launch Date: Immediately
• Estimated Cost: a one-time cost of $515,000
• The American Cancer Society estimates that over 100,000 new cases of melanoma are diagnosed each year in the U.S. Although only a small percentage of cases advance into metastases, roughly 8,300 Americans die from melanoma annually.
• The five-year survival rate for widely metastasized melanoma is around 35%.
• Amtagvi uses TIL cells from a patient’s tumor, which are cultured in a laboratory for about one month to increase the number of active cells and then infuse them back into the patient.
• Amtagvi will be used after treatment with a programmed death receptor-1 (PD-1)-blocking antibody, such as Keytruda^® (pembrolizumab), fails. If the tumors are positive for BRAF V600 mutations, a BRAF inhibitor such as Braftovi^™ (encorafenib) with or without a MEK inhibitor, such as Mektovi^® (binimetinib), also must have been tried.
• Amtagvi will be administered in about 50 medical facilities that are equipped to perform the procedures and that have staff specially trained to do cell harvesting, infusion, and follow-up.
• Patients will be hospitalized before and after the infusion and they are advised to stay within a two-hour radius of the treatment facility for several weeks after the procedure.
• In clinical trials, approximately 30% of patients who received Amtagvi responded to treatment with it (objective response rate, ORR) and the responses averaged at least one year for 44% of responders in one study and 54% in the other one.
• Amtagvi has a boxed warning because it was responsible for severe side effects including extended and dangerously depressed numbers of blood cells, severe infections, cardiopulmonary problems, kidney damage, and death among study participants.
• Other side effects, such as diarrhea, fatigue fever, low blood pressure, and rash, were reported by patients in the trials.
• Designated as an Orphan Drug and a Regenerative Medicine Advanced Therapy, Amtagvi was approved under the FDA’s Fast Track and Priority Review.
• Since Accelerated Approval for Amtagvi is based on results from uncompleted clinical studies, additional positive results from more advanced trials will be needed before full FDA approval is granted.