Earlier today the U.S. Food and Drug Administration announced the approval of ipilimumab (Yervoy, Bristol-Myers-Squib Company), an immunotherapy treatment to treat patients with advanced or late-stage (metastatic) melanoma. This new treatment option is the first therapy in more than thirteen years available to treat the most lethal form of skin cancer ? melanoma. The drug will be used to treat melanoma patients whose cancer has spread to other parts of the body. It is the first approved drug that has extended the lives of patients with advanced melanoma.
Melanoma, the most serious type of skin cancer, is one of the fastest growing cancers in the United States and can strike men and women of all ages, all races and skin types. In fact, with a one in 50 lifetime risk of developing melanoma, nearly 68,130 Americans were expected to be diagnosed with the disease in 2010, resulting in 8,700 deaths or one person every hour. Melanoma is the most common form of cancer for young adults 25- to 29-years-old and the second most common cancer in adolescents and young adults 15- to 29-years-old.
?Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient?s life,? said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA?s Center for Drug Evaluation and Research. “Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment.”
“This is a critical breakthrough for advanced-stage melanoma patients who have far too few approved treatment options available,” said Timothy J. Turnham, the executive director of the Melanoma Research Foundation (MRF), the largest independent, national organization devoted to melanoma in the United States. “Patients have been waiting for a life-changing innovation like this one and news of the approval has galvanized the patient community.”
Melanoma is among the most difficult cancers to treat and is the deadliest skin cancer. For patients diagnosed with the advanced stages of the disease, the median lifespan is less than one year. The last therapeutic to be approved for melanoma, Interleukin-2, only benefits 10-15% of those with advanced melanoma.
Ipilimumab is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body?s immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body?s immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously.
Ipilimumab?s safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed. The study was designed to measure overall survival, the length of time from when this treatment started until a patient’s death. The randomly assigned patients received Ipilimumab plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone. Patients who received the combination of Ipilimumab plus the vaccine or Ipilimumab alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.
Earlier this week, Bristol-Myers Squibb Company also announced that a clinical trial, known as study 024, of ipilimumab has met the primary endpoint of improving overall survival in previously-untreated patients with metastatic melanoma. Study 024 was designed to assess overall survival in unresectable stage III or stage IV melanoma patients who have not received prior therapy. The study compares ipilimumab 10mg/kg in combination with chemotherapy (dacarbazine) vs. chemotherapy alone. An abstract of the 024 data will be submitted to the American Society of Clinical Oncology for potential presentation at the Annual Meeting in June of this year.
Important step forward
?For the first time, oncologists have a treatment option for patients with unresectable or metastatic melanoma that has been proven in a randomized Phase 3 clinical trial to significantly extend the lives of patients,? said Steven J. O?Day, M.D., Chief of Research and Director of the Melanoma Program at The Angeles Clinic and Research Institute, California, and an investigator of the registrationtrial. ?In fact, the Kaplan-Meier curve from this study suggests a prolonged survival benefit for some patients.? Median overall survival was 10 months (95% CI: 8.0-13.8) for ipilimumab, 6 months (95% CI: 5.5-8.7) for gp100 and 10 months (95% CI: 8.5-11.5) for ipilimumab + gp100, with p-values of 0.0026 (not adjusted for multiple comparisons) for ipilimumab and 0.0004 for ipilimumab + gp100 vs gp100, respectively.
?The FDA approval of ipilimumab is the culmination of more than 14 years of research and development by our dedicated development teams and clinical trial investigators,? said Elliott Sigal, M.D., Ph.D., executive vice president, chief scientific officer, and president, Research & Development, Bristol-Myers Squibb. ?Ipilimumab is the first FDA-approved compound from our robust immuno-oncology pipeline, which comprises a variety of other compounds with the potential to harness the patient?s immune system to fight cancer.? The mechanism of action of ipilimumab?s effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumor immune responses.
“The FDA’s decision to approve ipilimumab is an important step forward for melanoma patients, but the work isn’t done,” Turnham said. “Until all patients have an option that can treat or cure their disease, we need to redouble our efforts.” Similar to the advances that were made in the development of “drug cocktails” for patients with HIV/AIDS, most melanoma researchers agree that testing combination therapies, including using Yervoy, is the key to achieving significant strides for a broader spectrum of patients.
With approval comes a major shift in the treatment landscape for patients. As patients work to discern their options, connecting with other patients becomes more critical. The MRF hosts the Melanoma Patient Information Page, which is the leading online community gathering spot for melanoma patients.
“As this exciting new therapy becomes available, patients will no doubt have many questions about their personal treatment options,” Turnham said. “The MRF is dedicated to facilitating conversations among patients and encouraging information sharing that is critical to successfully fighting melanoma.”
The MRF, the largest independent, national organization devoted to melanoma in the nation, is committed to funding medical research to find effective treatments and eventually a cure for melanoma. The MRF has invested more than $1 million in research grants to support the development of new treatments, including early phases of research for ipilimumab.
Researchers have started to uncover that melanoma is actually many different diseases, each with its own unique biology. As a result, successful treatment may require targeted and personalized therapies to treat patients effectively. Melanoma researchers are working to translate that understanding into therapies that might have a meaningful impact on the survival of patients. The MRF’s support of combination trials of therapeutics has translated into the development of a clinical trial that will be launched in the fall of 2011.