PARIS, July 14, 2011 /PRNewswire/ --
- First and Only Approved Therapy for Pre-treated Unresectable
or Metastatic Melanoma to Demonstrate a Significant Improvement in
Overall Survival
- First EU-Approved Therapy for Pre-treated Unresectable or
Metastatic Melanoma in More Than Two Decades
Bristol-Myers Squibb today announced that the European Commission has approved YERVOY(TM) (ipilimumab) for the treatment of adult patients with previously-treated advanced melanoma.
YERVOY, an innovative immunotherapy, showed long-term survival in the treatment of patients with advanced melanoma in a randomised, double-blind Phase III study published in the New England Journal of Medicine in June 2010.[1] Based on the survival (Kaplan-Meier) curve, the 1 and 2-year estimated survival rates for patients treated with YERVOY were 46% and 24% respectively vs. 25% and 14% in the comparator arm with some patients alive at 3 and 4 years.
"With the approval of YERVOY physicians now have an important new option to offer to patients with metastatic melanoma. This is a chance of not just months but potentially 3 to 4 years of prolonged survival for some patients in the treatment of metastatic melanoma," comments Professor Alexander Eggermont, General Director, Institut Gustave Roussy, Paris, France. "There is hope that YERVOY's novel mode of action, together with the fact that the recommended complete course of treatment with YERVOY (3 mg/kg) includes 4 infusions over 3 months, could potentially change the way we treat patients with previously treated advanced melanoma. It is an example of what can be done through unleashing the power of one's own immune response."
Bristol-Myers Squibb will now work closely with local health authorities to expedite the availability of YERVOY across the European Union. Prior to approval, the Company provided ipilimumab to nearly 3,000 patients throughout Europe through Compassionate Use / Named Patient Programmes. The Company remains committed to helping ensure that appropriate patients who need YERVOY will receive it while the reimbursement process is finalised by the relevant authorities throughout Europe.
Ron Cooper, President Bristol-Myers Squibb Europe, stated:"With an average survival time on diagnosis of 6-9 months, patients with advanced melanoma have had little hope - until now. The European Union approval of YERVOY is a milestone for patients with advanced disease and is the first outcome of Bristol-Myers Squibb's commitment to immuno-oncology. Through the Bristol-Myers Squibb String of Pearls strategy, we began a collaboration with Medarex, acquired the company and developed YERVOY. We will continue this strategy to seek and establish collaborations with other leading innovators across the globe. Through these and other initiatives we work towards our single mission: to discover, develop and deliver innovative medicines that help patients prevail over serious diseases."
YERVOY represents a new treatment paradigm in the evolving discipline of immuno-oncology. It indirectly targets the tumour by stimulating the patient's immune system to recognise and destroy cancer cells.[2] YERVOY specifically blocks cytotoxic T lymphocyte antigen 4 (CTL4), which plays a role in suppressing the normal immune response. YERVOY blocks that suppression to allow the immune system to respond to melanoma cancer cells.
The types of adverse events (AEs) attributed to YERVOY are generally mechanism (immune)-based. YERVOY can result in severe and fatal immune-related adverse reactions due to T-cell activation and proliferation. These immune-mediated reactions may involve any organ system; however, the most common severe immune-mediated adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated reactions initially manifested during treatment; however, a minority occurred weeks to months after discontinuation of YERVOY. Patients should be assessed for signs and symptoms of enterocolitis, dermatitis, neuropathy and endocrinopathy and clinical chemistries should be evaluated, including liver function tests and thyroid function tests, at baseline and before each dose.
Adverse events associated with YERVOY are managed with protocol-specific guidelines, including the administration of systemic corticosteroids, dose interruption/discontinuation and/or other immunosuppressants.
About Advanced Melanoma
Melanoma is a form of skin cancer characterised by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin.[3] Advanced 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. Some cancer cells can actively evade surveillance by the immune system, allowing tumours to survive.
Melanoma is mostly curable when treated in its early stages.[4] However, metastatic melanoma is one of the most aggressive forms of cancer with 75% of people dying within one year.[5] Due to the very poor prognosis and lack of effective treatments for patients with stage III unresectable and stage IV metastatic melanoma, there remains a significant unmet medical need.
Unlike most other solid tumours, melanoma affects younger, middle aged people. The median age at diagnosis for melanoma is 57 and the median age at death is 67.[6]
About YERVOY (ipilimumab)
YERVOY, which is a recombinant, human monoclonal antibody, blocks the cytotoxic T- lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation. YERVOY binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation. The mechanism of action of YERVOY's effect in patients with melanoma is indirect, possibly through T-cell mediated anti-tumour immune responses.
On 25th March 2011, the US Food and Drug Administration (FDA) approved YERVOY 3 mg/kg for the treatment of patients with unresectable (inoperable) or metastatic melanoma in the US.
About the Reference Data - MDX010-020 Study: Improved Survival with Ipilimumab in Patients with Pre-Treated Metastatic Melanoma
The approval is based on a Phase 3, double-blind study that randomized 676 patients with unresectable or metastatic melanoma who were previously treated with one or more of the following: aldesleukin, dacarbazine, temozolomide, fotemustine, or carboplatin.Patients were randomized in a 3:1:1 ratio to receive either YERVOY (ipilimumab) (3mg/kg) in combination with the investigational peptide vaccine gp100 (n=403), YERVOY alone (3mg/kg; n=137), or gp100 alone (n=136).
The primary endpoint of the pivotal Phase 3 study was overall survival in the YERVOY plus gp100 arm vs. the gp100 arm. Secondary efficacy endpoints included overall survival in the YERVOY plus gp100 arm vs. the YERVOY arm, overall survival in the YERVOY arm vs. the gp100 arm, Best Overall Response Rate ("BORR") at week 24 and duration of response.
Patients received YERVOY (3mg/kg) as an intravenous infusion administered over 90 minutes every 3 weeks for four doses. Assessment of tumor response to YERVOY was conducted at weeks 12 and 24, and every 3 months thereafter. Patients with evidence of objective tumor response at 12 or 24 weeks had assessment for confirmation of durability of response at 16 or 28 weeks, respectively. Between 57% and 64% of patients treated in each study arm received all four planned doses.
(CONTINUA)
