Today LA times (business section) has short article on Abgenix (ABGX). Issue is GVHD and their antibody, ABX-CBL. Here is press release for this trial.
What did intrigue me is medical cost of complicated BMT (accompanied with GVHD): +250K in addition to 60-100K for BMT. If GVHD drugs are only 10% of therapy, than opportunity are tremendous.
The point is that T results for GVL/GVHD (abstract repeated) are comparable with ABX-CTL, and with addition of activity to leukemia. This may be nice opportunity for CELG and reasonable T-therapy cost.
Miljenko
Abgenix Reports Positive Preliminary Results From a Phase II Trial of
ABX-CBL In Graft Versus Host Disease
Phase III Clinical Trial Expected to Begin in Mid-1999
FREMONT, Calif., Feb. 4 /PRNewswire/ -- Abgenix, Inc. (Nasdaq: ABGX)
reported today results of a Phase II clinical trial of ABX-CBL in graft versus
host disease ("GVHD"). ABX-CBL is a proprietary in-licensed mouse antibody
that binds to the CBL antigen. The CBL antigen is over-expressed on activated
immune cells, including T cells, B cells and natural killer cells. The
completed trial involved patients in four dose cohorts with severe GVHD, an
often fatal side effect of bone marrow transplants ("BMT"). Among patients in
the three higher dose cohorts, 73% (11 of 15) had a two grade or better
improvement in GVHD. This compared favorably to a 25% (2 of 8) response rate
in the low dose cohort. Joachim Deeg, M.D., of the Fred Hutchinson Cancer
Center in Seattle, Washington, will present details of the clinical trial in
March, at the upcoming International Bone Marrow Transplant Registry ("IBMTR")
meeting in Keystone, Colorado.
"We are pleased with results of this trial which supports the safety and
efficacy seen in earlier published clinical trials conducted by others,"
stated R. Scott Greer, president and chief executive officer of Abgenix. "We
plan to initiate a pivotal Phase III clinical trial for ABX-CBL as soon as
feasible after we have approval from the FDA to proceed."
The Phase II clinical trial was conducted at nine sites and involved
27 patients evaluated for safety, 23 of which were also evaluated for efficacy
end points. A clinical response was defined as a two grade improvement in the
IBMTR GVHD Severity Scale. GVHD is graded based on clinical symptoms from
grade I, which is the mildest form, to grade IV, which is the most severe
form. Two of eight patients responded in the lowest dose cohort (.01 mg/kg)
which was presumed to be a no effect dose. Eleven of 15 patients responded in
the 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg dose cohorts. Due to temporary muscle
pain during infusions, 0.3 mg/kg was considered the maximum tolerated dose.
We believe the treatment was safe and well tolerated except for the observed
muscle pain.
GHVD is a life threatening complication that frequently occurs following
an allogeneic BMT. BMTs are used in the treatment of patients with end stage
leukemia, certain other serious cancers and immune system disorders. An
allogeneic BMT procedure involves transferring marrow, the graft, from a
healthy person into an immunosuppressed patient, the host. The transplant is
intended to restore normal circulating immune cells to a patient whose own
immune system is functionally deficient or has been damaged by the treatment
of an underlying disease such as cancer and therefore does not have the
ability to mount a sufficient immune response. Often a portion of the graft
recognizes the host's own cells as foreign, becomes activated and attacks
them, resulting in GVHD. It typically involves damage to multiple organ
systems, including the skin, liver and intestines. GVHD causes extreme
suffering and is the primary cause of death in allogeneic BMT patients.
It is estimated that approximately 12,000 allogeneic BMTs were performed
worldwide in 1998, and this number has been growing at about 15% per year.
GVHD occurs in approximately 50% of allogeneic BMTs and the treatment costs
for GVHD in the United States are estimated to be about $80,000 per patient.
Based on a published clinical study, it is estimated that roughly 50% of
patients with GVHD fail to respond to current treatments, which consists of
steroid and other drug treatments to suppress the grafted immune cells.
Abgenix is a biopharmaceutical company that develops and intends to
commercialize antibody therapeutic products for the treatment of a variety of
disease conditions, including transplant-related diseases, inflammatory and
autoimmune disorders, cardiovascular disease and cancer. Abgenix has
developed XenoMouse technology, a proprietary technology, which Abgenix
believes enables quick generation of high affinity, fully human antibody
product candidates to essentially any disease target appropriate for antibody
therapy. Abgenix has collaborative arrangements with eight companies
including Cell Genesys, Inc., Pfizer Inc., Schering-Plough Research Institute,
Genentech, Inc., Millennium BioTherapeutics, Inc., Research Corporation
Technologies, Inc., Centocor, Inc., and AVI BioPharma, Inc. In addition,
Abgenix has four proprietary antibody product candidates that are under
development internally, two of which are in human clinical trials.
Statements made in this press release about Abgenix's clinical trials for
ABX-CBL, XenoMouse technology, product development activities, clinical trials
for other product candidates, product pipelines and collaborative arrangements
other than statements of historical fact, are forward looking statements and
are subject to a number of uncertainties that could cause actual results to
differ materially from the statements made, including risks associated with
the success of clinical trials for ABX-CBL and Abgenix's other product
candidates, the progress of research and product development programs, the
regulatory approval process, competitive products, future capital requirements
and the extent and breadth of Abgenix's patent portfolio. Please see
Abgenix's public filings with the Securities and Exchange Commission for
information about risks which may affect Abgenix.
Miljenko
Abstract #4482 (publish only)
THALIDOMIDE IN GVHD - IS ANTI-GVHD EFFECT SEPARABLE FROM THE ANTIANGIOGENESIS
S. Kulkarni*, R. Powles, J. Mehta, C. Horton*, J. Treleaven*, S. Meller*, A. Atra*, C.R. Pinkerton*, S. Singhal
Royal Marsden Hospital, Surrey, UK
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The outcome of patients with steroid-refractory acute or chronic GVHD is poor. We have evaluated thalidomide extensively in both situations. Recently it has been shown that thalidomide has anti angiogenesis action and can be used as anti leukaemia agent. This analysis was undertaken to find the effect of thalidomide in inducing response in GHVD (especially chronic) and see if the anti GVHD (and anti-GVL) effect can be compensated by anti-angiogenesis effect by changing the relapse incidence. 41 patients (29M, 12F, 4-52 y, median 28) with hematologic malignancies who develop limited (n = 17) or extensive (n = 24) chronic GVHD after BMT from matched siblings (n = 35) or unrelated donors (n = 6) received the drug (50800 mg/d, median 600) after responding inadequately to previous therapy with cyclosporine (n = 28), corticosteroids (n = 37), azathioprine (n = 25), tacrolimus (n = 1), murine anti-IL-2 receptor antibody (n = 1), or methotrexate (n = 1). The duration of therapy was 1 day to 2 years (median 60 days). Response was inevaluable in 8 because of short treatment duration (<2 weeks 0 as a result of GVHD-related death (n = 5) or adverse effects requiring drug discontinuation (n = 3). 20 patients did not respond, 9 patients had complete/excellent partial resolution of GVHD, and 4 had some improvement. The overall response rate was 39.4% (13 of 33). Four patients with bronchiolitis obliterans organizing pneumonia (BOOP) showed no change in pulmonary status on thalidomide. One patient developed peripheral neuropathy after 2 years of treatment. The drug was stopped due to drowsiness in 4, and the dose had to be reduced in 1. Six had constipation and one thrombocytopenia. Currently 17 patients are alive, including 9 responding to thalidomide. 24 including 4 thalidomide responders, died of complications of GVHD (n = 17), relapse (n = 3), interstitial pneumonitis (n = 2), or second cancers (n = 2). Two patients with chronic GVHD relapsed (1 each of AML and CML). The relapse rate was 4.9%. Both the relapses occured in non-responders to thalidomide and both died due to relapsed leukaemia. Since 22/41 had advanced disease at the time of presentation this relapse rate may be considered as low. Weather this is the effect of extensive GVHD or the anti-angiogenesis effect of thalidomide is contributory certainly needs investigation. We conclude that thalidomide is activity in chronic GVHD. Its anti-angiogenesis properties and effect on leukaemia relapse needs to be evaluated.
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