Medarex, Inc. and its partner Bristol-Myers Squibb Company said top-line data from three registrational trials (008, 022, 007) of its skin cancer drug ipilimumab did not meet the primary endpoint. However, the companies said they have planned to seek approval for ipilimumab with the US Food and Drug Administration in the first half of 2008.

The results from study 008, conducted under Special Protocol Assessment (SPA), did not meet the primary endpoint, which was to rule out a best objective response rate of less than 10 per cent. However, the totality of data from the registrational programme included a clear dose response effect observed in study 022 and best objective response rates across the three studies ranging from mid-single digits to mid-teens as determined by independent radiology review.

The objective responses were consistent with previous observations and included complete and partial responses. The majority of the responses were ongoing at the end of the observation period. In contrast to standard cytotoxic therapy, responses at the highest doses were noted to evolve over time; these patterns of response appear potentially unique to this form of therapy.

Given the importance of these findings and the limited treatment options for this patient population, Medarex and Bristol-Myers Squibb are planning to meet with regulatory agencies in the near future. Pending these discussions, the companies aim to submit a regulatory filing to the US Food and Drug Administration (FDA) in the first half of 2008.

Overall, the safety results from the three studies were generally consistent with data from previously reported clinical trials of ipilimumab and, as expected, the most common immune related adverse events (greater than five percent) consisted of rash, diarrhoea, and hepatitis. Safety data from the 10 mg/kg cohorts were consistent with results from similar or lower doses of previously reported clinical data.

The registrational, monotherapy programme evaluated ipilimumab in 487 patients with advanced stage III or stage IV metastatic melanoma from three clinical trials conducted at multiple centres across North America, Europe, South America and Africa. The trials included an open-label, single arm trial (008) evaluating overall response rate in 155 patients who progressed on or following standard treatment; a randomised, double-blind trial (022) evaluating the efficacy of three dose levels of ipilimumab in 216 patients who were previously treated.

All three studies were designed to capture clinical activity and kinetics of response at specific time points, beginning with an initial assessment at 12 weeks. Objective response determinations were verified by an independent radiology committee. Active follow-up of patients is ongoing, and many patients enrolled in the three studies are continuing to be treated with maintenance therapy.

Initiation of the ipilimumab registrational monotherapy program reviewed under SPA with the FDA was announced in March 2006. Following the March 2006 announcement, enrolment of 487 patients was completed in less than one year and in line with timeline expectations. In December 2006, ipilimumab received Fast Track designation from the FDA for use as a monotherapy in previously treated patients with metastatic melanoma.

Ipilimumab is a fully human antibody that binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4), a molecule on T-cells that plays a critical role in regulating natural immune responses. Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin.