Raphael Thys
Dendritic cell activates T cells which in turn trigger immune responses. Amtagvi is the first first
Based on Phase 2 data, the Food and Drug Administration has granted an accelerated approval of a promising cellular immunotherapy, Amtagvi (lifileucel), to treat advanced forms of melanoma. The accelerated approval pathway relies on surrogate endpoints rather than clinical benefit measured in terms such as extension of life or improvement of morbidity outcomes. A confirmatory Phase 3 trial is ongoing to verify Amtagvi’s clinical effectiveness. If this is demonstrated, Amtagvi will represent an important breakthrough.
Amtagvi is the first cell therapy approved by the FDA for solid tumors. It is also the first marketed treatment that uses tumor-infiltrating lymphocytes collected directly from a tumor sample and fortified in a laboratory to better fight the cancer, as PharmaVoice explains.
The newly approved medicine is similar to CAR T-cell therapies, which have mainly been used to treat blood cancers. While they can typically help combat cancer, T-cells tend to become dysfunctional inside tumors. During the CAR T-cell therapy process a patient’s immune system T-cells are extracted from their tumor, genetically modified and subsequently reinserted into the patient to attack malignant cells.
While CAR T-cell therapies have proven to be effective in blood cancers, they haven’t performed as well in solid tumors. As a one-time treatment, the T-cell therapy Amtagvi demonstrated the ability to treat a solid tumor durably.
Amtagvi is not a first-line therapy. Standard treatment for unresectable or metastatic melanoma first involves immunotherapy using PD-1 inhibitors, which are antibodies targeting certain proteins in the body to help the immune system fight off cancer cells. In addition, drugs such as Zelboraf that target the BRAF gene, which help manage the growth and functioning of cells, may be prescribed for treating melanoma associated with BRAF gene mutations.
Amtagvi is intended for patients who were previously on an immuno- and targeted therapy agent and failed, whose melanoma cannot be removed with surgery and whose cancer has spread to other parts of the body. The treatment will be available in approximately 40 treatment centers for melanoma patients nationwide.
Melanoma only accounts for 1% of all skin cancer cases. The American Cancer Society estimates that in 2024, about 100,000 new cases of melanoma will be diagnosed and about 8,000 people will die. Melanoma develops when the skin cells that produce pigment begin to grow out of control. A major risk factor is extensive exposure of unprotected skin to ultraviolent light, which can come from the sun or tanning beds. The disease is comparatively easy to treat if detected early. But if it's not removed in time, the malignancy can spread to other parts of the body.
For patients whose melanoma has progressed in spite of being on immunotherapies Amtagvi addresses an unmet need.
Amtagvi’s manufacturer Iovance Biotherapeutics has priced the therapy at $515,000, which makes it the most expensive cell-based treatment in the U.S. Though as a cancer treatment it will likely be covered by most insurers, Amtagvi will invariably be tagged with prior authorization protocols.
The process of administering therapy is complex. It involves multiple steps which can take a month or so to carry out. This includes an initial surgery to harvest the tumor specimen that is sent to Iovance’s manufacturing sites for what is called ex vivo expansion. The patient then must undergo lymphodepleting chemotherapy before ultimately receiving the infusion. To get all this paid for requires passing through insurers’ a number of prior authorization hoops, which can take several weeks to accomplish.
The price tag and elaborate and costly treatment process will undoubtedly present a challenge to payers, especially ones that are more cash-strapped like Medicaid. But on a recent earnings call the cell therapy’s sponsor, Iovance, expressed confidence in securing reimbursement for the product consistent with the FDA label, albeit with prior authorization protocols in place.
Indeed, Amtagvi’s launch appears to be off to an encouraging start, with 20 patients enrolled in just two weeks since approval, according to Endpoints News.
One of the bigger tests now is passing the confirmatory trial. Ultimately, having certainty of clinical benefit would not only allay payer concerns, it would also increase patient and physician demand for the product.