Initial Phase I/II Study Data
COPENHAGEN, Denmark | Mar 08, 2006 | Genmab A/S (CSE: GEN) announced today positive results in the HuMax-CD20™ Phase I/II dose escalation study to treat patients with active rheumatoid arthritis (RA). In patients who received two doses of HuMax-CD20, 77% (20/26) obtained ACR20. Even on an intent to treat basis, which included six patients who did not receive both doses of HuMax-CD20, 63% (20/32) obtained an ACR20. For comparison, among the 7 placebo patients none achieved ACR20.
There were three dose levels tested in the study. In the lowest dose group, (300 mg), 75% (6/8) of patients who received both doses obtained ACR20. In both the 700 and 1000 mg dose groups, 78% of patients who received both doses obtained ACR20 (7/9 per group).
The study included 39 patients and 33 received either two infusions of HuMax-CD20 or placebo, given 2 weeks apart. The primary objective of the study was safety. Efficacy was assessed by the ACR score at week 24.
Patients in this study had previously failed at least one disease modifying anti-rheumatic drug (DMARD). In addition 26 of the 39 had previously received treatment with TNF inhibitors. Twenty-two were intolerant or refractory to TNF inhibitors and four stopped for other reasons. Efficacy among these patients was in the same range as for the rest of the group on an intent to treat basis.
The maximum tolerated dose has not been reached. 2 infusion-related serious adverse events and a common terminology criteria (CTC) grade 3 event were observed in the 300 mg cohort. Consequently pre-medication with corticosteroids was implemented and further intensified for the 700 mg and 1000 mg cohorts where 2 patients reported infusion-related CTC grade 3 events.
In August 2005, the study was expanded into a Phase II trial which will include 200 additional patients.
The data will be presented at the 10th Anniversary Inflammation and Immune Diseases, Drug Discovery and Development Summit in New Brunswick, New Jersey 21 March 2006 by Dr. Mikkel Østergaard, Professor of Rheumatology at Hvidovre Hospital.
“The initial results of this Phase I/II study in RA are very encouraging,” said Lisa N. Drakeman, Ph.D., Chief Executive Officer of Genmab. “We are looking forward to the ongoing development of HuMax-CD20 in RA.”
Conference Call
Genmab will hold a conference call to discuss the news today, March 8, 2006 at:
3.30 pm CET
2.30 pm GMT
9.30 am EST
The dial in numbers are as follows:
+1 800-311-6662 (in the US) and ask for the Genmab conference call
+1 719-457-2696 (outside the US) and ask for the Genmab conference call
The conference call will be held in English.
About the study
The study is a double-blind, randomized, placebo controlled multi center phase I/II trial of HuMax-CD20. Patients with active RA, who have previously failed one or more DMARDs, received two infusions of either HuMax-CD20 (300, 700 or 1000 mg) or placebo 2 weeks apart. The trial is comprised of a three-cohort, dose escalation Phase I/II with the primary objective to evaluate safety and an ongoing Phase II study in 200 patients to evaluate efficacy. Continuation of ongoing therapy with stable doses of methotrexate and low dose corticosteroids was allowed. Previous exposure to biological agents was allowed except for anti-CD20 antibodies within 2 years prior to inclusion.
About Rheumatoid Arthritis
Rheumatoid Arthritis is a systemic inflammatory disease which affects 0.8-1% of all populations, approximately 2 million people in the US alone.
ACR20 Response
An ACR20 response indicates a 20% improvement in number of swollen and tender joints, as well as a 20% improvement compared with baseline in three of five disease-activity measures: patient assessment, physician assessment, pain scale, Health Assessment Questionnaire and the value for one measure of acute disease activity (erythrocyte sedimentation rate or C-reactive protein).
About HuMax-CD20
HuMax-CD20 is a fully human antibody which binds to the CD20 antigen on the surface of B-cells. From there, it recruits the body's natural defenses to attack and kill the marked B-cells. 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. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and return to normal levels within several months.
SOURCE: Genmab A/S |
