BY OUR PHARMA CORRESPONDENT
18th August,2005: Genmab A/S has begun a phase II study with HuMax-CD20 to treat patients with active rheumatoid arthritis (RA) who have failed one treatment with one or more disease modifying anti-rheumatic drugs (DMARDs). Genmab has completed treatment of 33 patients in a phase I/II dose escalation trial and expanded the study into a phase II trial, which will include 200 additional patients, a company statement announced.
In the phase II trial, a total of 200 patients will be randomized into four treatment groups. In each group, 50 patients will receive two infusions of either 300, 700, or 1000 mg doses of HuMax-CD20 or placebo. The doses will be given two weeks apart. Patients receiving a stable dose of methotrexate between 7.5 and 25 mg per week at the time of screening will continue with it. Patients will be followed for 24 weeks to evaluate safety and efficacy and then every 12 weeks until B-cell counts return to baseline levels.
HuMax-CD20 is a human antibody which is effective at binding to the CD20 molecule on B-cells. In June 2005, Genmab presented positive data from a phase I/II trial with patients with relapsed or refractory follicular lymphoma showing response rates up to 63% in patients treated with HuMax-CD20.
Genmab A/S had earlier reported safety data at the 9th International Conference on Malignant Lymphoma in Lugano, Switzerland at all dose levels of HuMax-CD20 in a phase I/II safety study to treat patients with relapsed or refractory follicular non-Hodgkin’s lymphoma (NHL). Objective response rates of up to 63% according to Cheson criteria were observed in patients still in follow-up. Final data is expected to be presented at the end of 2005.
Patients were given 4 weekly infusions of HuMax-CD20 at doses of 300, 500, 700 and 1000 mg. Tumor response was assessed 8, 16 and 23 weeks after the final infusion of HuMax-CD20. Objective responses at each dose level were 63% (300 mg dose), 33% (500 mg dose), 20% (700 mg dose) and 56% (1000 mg dose). These response rates include 5 complete responses (CR), 2 complete responses unconfirmed (CRu) and 8 partial responses. A CRu meets and exceeds the criteria for partial response.
An objective response rate of 57% was achieved by 14 evaluable patients who previously responded to rituximab treatment including 3 CR and 1 CRu for a 29% complete response rate. Immediate, profound depletion of B-cells was seen at all dose levels. This depletion has generally been maintained in the follow up period to date.
No dose limiting toxicities were reported during the study and the maximum tolerated dose was not reached. The most frequently reported adverse events were rigors, fatigue, headache and rash. Hematological toxicity was low with only 6 of 40 patients reporting grade 1 neutropenia and no patients reporting thrombocytopenia.
A phase I/II trial to treat patients with chronic lymphocytic leukemia is ongoing.
The CD20 antigen is a transmembrane protein on pre-B and mature B lymphocytes. CD20 appears to act as a calcium ion channel, and to regulate early steps in B lymphocyte activation. The molecule is not shed from the cell surface, and is not internalized upon antibody binding. CD20 is found on over 90% of B-cell lymphomas, as well as other lymphoid tumors of B-cell origin. B-cells are crucial pathogenic elements in the induction and pathogenesis of RA. As B-cells are involved in various cellular interactions with immune cells, B-cell depletion after HuMax-CD20 treatment can be expected to affect RA disease activity.
Rheumatoid arthritis (RA) is a systemic inflammatory disease which affects 0.8-1.0% of all populations.
Genmab A/S is a biotechnology company that develops human antibodies. Genmab has numerous products in development to treat cancer, infectious disease, rheumatoid arthritis and other inflammatory conditions, and intends to continue assembling a broad portfolio of new therapeutic products. At present, Genmab has multiple partnerships to gain access to disease targets and develop novel human antibodies including agreements with Roche and Amgen. A broad alliance provides Genmab with access to Medarex, Inc.’s array of proprietary technologies, including the UltiMAbplatform for the rapid creation and development of human antibodies to virtually any disease target. Genmab is an international company with operations in Europe and the United States.
BY OUR PHARMA CORRESPONDENT