Genmab A/S announced that 55 per cent of higher dose patients in the primary indication (10/18) achieved at least a partial response in HuMax-CD4 Phase II cutaneous T-cell lymphoma (CTCL) studies. The higher dose levels in the Phase II study were 560 and 980 mg weekly for up to 17 weeks. These patients were all treated for mycosis fungoides (MF), which comprises 75 per cent of CTCLs. This patient population is expected to be the group treated in the upcoming pivotal study.

Fourteen early stage MF patients have been treated at the 560 mg dose level. Seven of them achieved at least a partial response (more than 50 per cent composite assessment score (CA) reduction for at least four weeks), including two who obtained a complete response (100 per cent CA score reduction for at least four weeks and confirmation by biopsy).

Four advanced stage MF patients have been treated at the 980 mg level and three of the four (75 per cent) obtained a partial response.

Nine patients with Sezary syndrome, another form of CTCL, were also treated in the Phase II studies, at all dose levels, 280, 560 and 980 mg. Four of the nine (44 per cent) obtained a 50 per cent CA score reduction with one obtaining a partial response. The observed response in these patients was generally short-lived and depletion of CD4 T-cells was limited. This patient group constitutes approximately 5 per cent of CTCL patients and is not expected to be included in the upcoming pivotal study.

There was a statistically significant dose response correlation in 38 early and late stage mycosis fungoides patients. In the 280 mg group 15 per cent (3/20) achieved a clinical response compared to 50 per cent (7/14) in the 560 mg group and 75 per cent (3/4) in the 980 mg group. In addition, CD4 T-cell depletion was more pronounced in patients treated with 560 or 980 mg compared to 280 mg and this effect was statistically significant.

HuMax-CD4 is considered to be safe and well tolerated in clinical trials to date. In total, 47 patients were treated in the Phase II CTCL safety studies at all dose levels. Based on judgments by the treating physicians, only five grade three events (hypersensitivity, elevated liver enzymes, aggravated pruritus [2 patients], and muscle fiber rupture) were considered related and six additional events, including five grade three and one grade four event were considered unrelated to HuMax-CD4 treatment.

"The results of the HuMax-CD4 extended Phase II studies are very encouraging and bring us one step closer to finding effective treatments for CTCL patients," said Lisa N. Drakeman, Ph.D., chief executive officer of Genmab.

The recognized composite assessment of index lesion disease activity (CA) is the primary endpoint for assessing clinical efficacy in the treatment of CTCL in the two ongoing clinical trials. When calculating the CA score, a maximum of five index lesions are assessed with regards to the following components; erythema, scaling, plaque elevation, hypo- or hyperpigmentation, and area. For the first four components values between 0 and 8 can be ascribed, whereas for the area of the index lesion values between 0 and 18 can be ascribed. The CA score is the sum of the assessments of erythema, scaling, plaque elevation, hypo- or hyperpigmentation, and area at a specific visit.

HuMax-CD4 is a high affinity human antibody that targets the CD4 receptor on T-lymphocytes. Genmab has run two Phase II studies concurrently using HuMax-CD4 to treat cutaneous T-cell lymphoma (CTCL), one in early stage patients and the other for patients with advanced disease.

The US FDA has designated HuMax-CD4 a Fast Track Product. This designation covers patients with cutaneous T-cell lymphoma (CTCL) who have failed currently available therapy. This patient group includes those who are refractory as well as those who cannot tolerate currently available treatment. Genmab is making plans for a pivotal study that is expected to begin in 2004.

T-cell lymphomas positive for the CD4 receptor constitute around 5% of Non Hodgkin's Lymphomas. The prevalence of MF is estimated at 16,000 to 20,000 in the US. MF patients tend to have a lifespan of 10 to 30 years and therefore may need treatment several times during the disease progression.

Non-cutaneous T-cell lymphomas that are positive for the CD4 receptor are predominantly of the nodal subtype. This includes peripheral and angioimmunoblastic T-cell lymphomas of which 75 per cent are CD4 positive and anaplastic large cell lymphomas of which 20 per cent are CD4 positive. The combined incidence of these lymphomas is approximately 2,770 in the US and Canada and 3,280 in industrialized Europe. Their prevalence in Europe is approximately 10,000 and in US and Canada it ranges from 8,000 to 10,000. Genmab is now making plans to initiate Phase II study in non-cutaneous T-cell lymphoma patients in the second half of 2004.