Genmab A/S announced positive early results of the first stage of the ongoing pivotal phase III study of HuMax-CD4 (zanolimumab) in cutaneous T-cell lymphoma (CTCL) and the ongoing phase II study in non-cutaneous T-cell lymphoma (NCTCL).

In the pivotal CTCL study, clinical response was shown in 5 of 12 patients (42 per cent) in the two highest dose groups. A partial response was obtained by 1 of 6 patients (16 per cent) in the 8 mg/kg dose group and 4 of 6 patients (67 per cent) in the 14 mg/kg dose group. Patients were also treated at the 4 mg/kg dose level, with no responses observed. This dose level is not being used in the second part of the ongoing pivotal study.

A total of 22 patients were enrolled in three dose cohorts in the first part of the pivotal study and received infusions of 4, 8, or 14 mg/kg of HuMax-CD4 once weekly for 12 weeks. Patients were evaluated 4 and 8 weeks after the final treatment dose and every 8 weeks until progression of disease. The goal of this first portion of the phase III study was to characterize material obtained from a new manufacturing site.

"We have successfully characterized the new HuMax-CD4 material and have moved into the second phase of the CTCL pivotal study," said Lisa N. Drakeman, Ph. D., Chief Executive Officer of Genmab. "We are encouraged by the response rates in these patients who have failed other therapies."

Preliminary results in the ongoing Phase II clinical trial in HuMax-CD4 to treat non-cutaneous T-cell lymphoma (NCTCL) showed that 4 of 14 patients (28.5 per cent) had objective responses. Plans are ongoing to next test HuMax-CD4 in combination with chemotherapy for the NCTCL patients.

Cutaneous T-cell lymphomas are a group of lymphomas characterized by abnormal accumulation of malignant T-cells in the skin, potentially resulting in the development of rashes, plaques and tumours. The most common types of CTCL include mycosis fungoides (MF) and Sézary syndrome (SS). CTCL result from errors in the production of T-lymphocytes or transformation of T-lymphocytes into malignant cells. Abnormal, uncontrolled growth and multiplication of malignant T-lymphocytes result in accumulation of these lymphocytes in the skin and may in some cases spread and affect the lymph nodes and other body tissues and organs, resulting in life-threatening complications.

Non-cutaneous T-cell lymphomas (NCTCL) are defined by highly malignant disease, which has localized to the lymph nodes even at the earliest stage of the disease, and include angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and unspecified peripheral T-cell lymphoma. NCTCL is characterized by aggressive progression with average survival time of approximately two years.

HuMax-CD4 is a human monoclonal antibody currently in Phase III development for cutaneous T-cell lymphoma (CTCL) and in Phase II for non-cutaneous T-cell lymphoma. These types of lymphomas express the CD4 receptor, which is the target of HuMax-CD4. In April 2005, Genmab and the United States Food and Drug Administration (FDA) reached an agreement on the design of its pivotal study protocol for HuMax-CD4 to treat CTCL under the Special Protocol Assessment process (SPA). The pivotal study includes patients with MF who are refractory to or intolerant of Targretin and one other standard therapy, and will treat a total of 88 patients.

In March 2004, Genmab announced that HuMax-CD4 had been designated a Fast Track Product by the US Food and Drug Administration (FDA). This designation covers patients with CTCL for whom no available therapy exists, i.e. have failed at least two systemic treatment regimens. HuMax-CD4 for the treatment of MF has also been granted Orphan Drug status in the US and Europe. HuMax-CD4 is being developed under a collaboration with Serono.