CANADIAN DRUG REVIEW PROCESS CONFIRMS CLINICAL BENEFITS OF YERVOY TO TREAT METASTATIC MELANOMA
BMS is committed to ensuring patients in provinces have access to this life-extending treatment
The pan-Canadian Oncology Drug Review (pCODR) made public today its initial recommendation for YERVOYTM (ipilimumab), which includes a positive clinical report. This initial guidance of the expert review committee is a reflection of the strong clinical evidence that supports the benefits of this treatment for metastatic melanoma, the deadliest form of skin cancer.
Bristol-Myers Squibb Canada “BMS Canada” will continue to collaborate with federal, provincial and territorial authorities to ensure patients in Canada have access to Yervoy through provincial and private drug plans as quickly as possible.
Melanoma is one of the fastest growing cancers in Canada and the second most common cancer in young adults aged 15 to 34. The incidence has more than tripled over the last 30 years and continues to increase. An estimated 5,500 Canadians will be diagnosed with melanoma this year and 950 will die from it. Advanced melanoma cases represent 15 per cent of new melanoma patients in Canada. It is estimated that 1,200 Canadians are living with unresectable melanoma. Melanoma is responsible for 75 per cent of the deaths associated with skin cancer.
Demonstrated survival with Yervoy
In a pivotal randomized phase three clinical study, the median overall survival was 10 months for Yervoy and six months for the comparator treatment, a peptide vaccine (gp100).
Furthermore, the Kaplan-Meier estimated survival rate with Yervoy at both one and two years was almost doubled when measured against patients treated with gp100, 46 per cent versus 25 per cent at one year and 24 per cent versus 14 per cent at two years. Yervoy also showed long-term survival with some patients alive at three and four years.
The types of adverse events (AEs) attributed to Yervoy are generally related to its mechanism of action, i.e., immune-based. Immune-mediated adverse reactions, sometimes fatal, include enterocolitis, intestinal perforation, hepatitis, dermatitis, neuropathy, endocrinopathy as well as toxicity in other organ systems.Adverse events associated with Yervoy are managed by the administration of systemic corticosteroids, dose discontinuation and/or the use of other immunosuppressants.
Mode of action
Unlike traditional chemotherapy, Yervoy is a first in class immunotherapy that specifically blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which plays a role in suppressing the normal immune response. In doing so, Yervoy indirectly targets the tumour by stimulating the patient’s immune system to recognize and destroy melanoma cells.
Also unlike most other medicines for advanced cancer, which are commonly given until the disease progresses, a complete course of treatment with Yervoy includes four infusions over a three-month period. Patients receive Yervoy every three weeks for four doses.
Yervoy is the first compound from Bristol-Myers Squibb’s robust immuno-oncology pipeline, which includes a variety of other compounds with the potential to harness the patient’s immune system to fight cancer. The company is an important player in the fight against cancer. It provided its first anti-cancer medication to Canadians more than four decades ago and continues to invest in research and development to respond to critical needs.
Melanoma is a rare but deadly form of skin cancer. It is characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Unlike many cancers, melanoma is clearly visible on the skin. Ninety per cent of melanomas are caused by exposure to UV light, including tanning beds.
Metastatic melanoma occurs when cancer spreads beyond the surface of the skin to other organs, such as the lymph nodes, lungs, brain or other areas of the body. Unresectable melanoma is a melanoma that cannot be removed or resected by surgery. The survival rate for melanoma is high if it is detected early but the advanced form, metastatic melanoma, is an aggressive disease which is often fatal.
The total direct and indirect cost of skin cancer in Canada in 2004 was estimated at $531.75 million, of which more than 80 per cent ($443.48 million) was from malignant melanoma.
Yervoy is a recombinant, human monoclonal antibody and the first approved cancer immunotherapy for melanoma to target the CTLA-4 (cytotoxic T lymphocyte-associated antigen-4), which plays a role in suppressing normal immune function.
Yervoy was approved by Heath Canada on February 1st 2012, by the United States Food and Drug Administration on March 25, 2011, and by the drug regulatory bodies of the European Union and Australia in July 2011.
In a pivotal randomized phase three clinical study, published in The New England Journal of Medicine, 676 patients in the study had all undergone previous treatment. The median overall survival was 10 months (95 per cent CI: 8.0-13.8) for Yervoy, six months (95 per cent CI: 5.5-8.7) for the comparator treatment (gp100) and 10 months (95 per cent CI: 8.5-11.5) for Yervoy + gp100, with p-values of 0.0026 (not adjusted for multiple comparisons) for Yervoy and 0.0004 for Yervoy + gp100 vs. gp100, respectively. The Kaplan-Meier estimated survival rate at one year was 46 per cent (95 per cent CI: 37.0, 54.1) in the Yervoy arm vs. 25 per cent (95 per cent CI: 18.1, 32.9) in the gp100 arm. The estimated survival rate at two years was 24 per cent (95 per cent CI: 16.0, 31.5) in the Yervoy arm vs. 14 per cent (95 per cent CI: 8.0, 20.0) in the gp100 arm. In the study, Yervoy showed long-term survival with some patients alive at three and four years.
Early diagnosis and appropriate management are essential to minimize life-threatening complications. Signs and symptoms suggestive of immune-mediated adverse reactions may be non-specific and should be considered Yervoy-related, unless an alternate etiology is identified. Most immune-mediated adverse reactions occurred during the treatment period; however, onset months after the last dose of Yervoy has also been reported.
In the phase three study, the most common adverse reactions were diarrhea (27 per cent), rash (26 per cent), pruritus (26 per cent), fatigue (24 per cent), nausea (23 per cent), vomiting (12 per cent), decreased appetite (11 per cent), and abdominal pain (11 per cent) for the Yervoy alone arm; diarrhea (29 per cent), rash (20 per cent), pruritus (18 per cent), fatigue (23 per cent), nausea (19 per cent), vomiting (9 per cent), decreased appetite (10 per cent), and abdominal pain (10 per cent) for gp100 arm. Ten per cent of patients treated with Yervoy and four per cent of patients treated with gp100 had to discontinue their therapy because of adverse reactions.
About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. Bristol-Myers Squibb Canada is a leading provider of medicines to fight cancer, cardiovascular and metabolic disorders, infectious diseases (including HIV/AIDS), nervous system diseases and serious mental illness. Bristol-Myers Squibb Canada's operations are headquartered in Montreal, Quebec.