Finding Balance through Innovation

Top 10 Innovations for 2011

#2 Anti-CTLA-4 Drug (ipilimumab): Targeted T-Cell Antibody for Metastatic Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells located in the skin. While anyone can develop melanoma, it is still not clear how all melanomas develop. Exposure to ultraviolet (UV) radiation clearly plays a big role. A history of sunburns, especially severe sunburns at an early age, have been shown to increase the risk of developing melanoma. In addition, exposure to UV radiation from indoor tanning increases the danger.

Melanoma usually occurs in adults, but it is sometimes found in children and adolescents. About 20% of all melanomas will spread. This cancer is not only resistant to most drug therapies, but when it moves to the brain, there is little that can be done to arrest its onslaught. Patients with late-stage melanoma have a 15% survival rate. Although melanoma accounts for barely 3% of skin cancer cases, it causes the most skin cancer deaths.

The incidence of metastatic melanoma has increased over the last 30 years, and the death rate has been increasing faster than that of most other cancers. There were approximately 68,000 new cases of melanoma in the United States in 2009, with 8,700 melanoma-related deaths.

A recent randomized study in the New England Journal of Medicine reported that about 23% of patients with advanced stage III or IV metastatic melanoma in 125 cancer centers who took an experimental anti-CTLA-4 drug called ipilimumab were still alive two years later, compared to 14% of those who did not receive the drug. On average, those taking ipilimumab survived 10 months, compared to the six months for those who received only a melanoma drug.

What ipilimumab does so well is specifically target the protein molecule, CTLA-4 (or cytoxic T-lymphocyte associated antigen 4), which is found on white blood cells and suppresses the immune system from fighting disease. When ipilimumab is taken, it acts as a T-cell potentiator, however, and blocks the action of CTLA-4, allowing the patient's immune system to fight the cancer more vigorously. Even though ipilimumab does not cross the blood-brain barrier, the newly activated T-cells do. Small studies with ipilimumab have reported that patients with brain metastases caused by melanoma experienced a 15-month response from the drug, on average.

The long-held dream of researchers to find a way to harness the patient's own natural defense system to destroy their cancer tumor cells is now getting closer to reality. The effectiveness of ipilimumab in melanoma therapy further confirms the role of immunotherapy as an effective therapeutic treatment, and there are now ongoing clinical trials with other promising immunotherapeutic drugs for patients with prostate cancer and neuroblastoma.

The FDA grants priority review status to medications that offer major advances in treatment, or that provide therapy where no adequate treatment exists. Based on its extraordinary response in improving the survival rates of patients with previously treated advanced melanoma, ipilimumab has received FDA priority review status and the approval of this life-saving drug is expected soon. If all goes as expected, ipilimumab will be the first new melanoma drug available in decades.