good results, now the major question is mechanism........
MedImmune and BioTransplant Announce Results of MEDI-507 Trial In Severe Steroid-Resistant
Graft-Versus-Host Disease Patients
GAITHERSBURG, Md., and CHARLESTOWN, Mass., July 12 /PRNewswire/ --
MedImmune, Inc. (Nasdaq: MEDI) and BioTransplant Incorporated (Nasdaq: BTRN)
today announced the presentation of data from a Phase 1/2 trial with MEDI-507
in patients with steroid-resistant, severe graft-versus-host disease (GvHD).
In the trial, 12 of 17 participants had improvement in their GvHD grade during
the follow-up period after treatment with MEDI-507; 10 patients achieved a
complete response (grade 0) at some point during the study. These results
were presented this week at the 28th Annual Meeting of the International
Society for Experimental Hematology. GvHD is a frequent and often fatal
outcome of bone marrow transplantation and is currently treated with
corticosteroids. The mortality rate for serious steroid-resistant GvHD cases
is estimated to be over 70 percent.
"We are encouraged by the responses seen in these severe GvHD patients who
were all unresponsive to standard steroid therapy," commented Edward Connor,
M.D., Vice President of Clinical Development at MedImmune. "GvHD is a very
difficult disease to treat; the data from this initial trial suggest
biological activity for MEDI-507 in GvHD."
Using the consensus classification based on biopsies, seven patients with
GvHD grade II and 10 patients with GvHD grade III-IV were enrolled in this
study. All but four of the patients had gut and/or liver involvement.
Patients received a short regimen of four doses of 0.12 mg/kg intravenous
MEDI-507 given every third day and then either placebo or additional doses of
0.12 mg/kg intravenous MEDI-507 weekly for four weeks. Patients were followed
for 100 days. Of the 17 patients in the trial, 12 improved their grade of
GvHD and 10 achieved grade 0 at some point during follow-up. Treatment with
MEDI-507 was generally well tolerated, and no antibodies to MEDI-507 were
detected. Eleven patients experienced acute adverse events associated with
MEDI-507, including chills, fever and nausea. These events were generally
mild and did not interrupt therapy. Notwithstanding improvements in GvHD in
certain patients, 12 of the 17 patients ultimately died during the 100 day
period, typically as a result of progression of their GvHD or complications
such as infections. These data were presented by the lead investigator of the
study, Voravit Ratanatharathorn, M.D., of the University of Michigan Hospital.
Dr. Connor added, "We have now gone on to begin a randomized, controlled
dose ranging study in steroid naive GvHD patients. We hope to optimize the
dose regimen to further improve and extend the clinical benefit. In addition
to the work we are doing in GvHD, we are also evaluating MEDI-507 in a Phase 1
trial in psoriasis patients."
"MEDI-507's ability to selectively block immune responses and to prevent
the rejection of transplanted cells or tissue is also an important part of
BioTransplant's ImmunoCognance(TM) approach," said Elliot Lebowitz, Ph.D.,
President and CEO of BioTransplant.
GvHD is a clinical syndrome caused when certain white blood cells from the
donor bone marrow attack the tissue of the recipient. Clinical manifestations
include skin rash, severe diarrhea, and liver abnormalities and jaundice.
Steroid-refractory GvHD occurs when the attacking white blood cells of the
foreign graft fail to respond to steroid therapy.
MEDI-507 is the humanized form of the murine monoclonal antibody, BTI-322.
In pilot clinical trials in over 100 patients in the United States and Europe,
BTI-322 has suggested potential clinical benefit in the studied populations
and has been generally well tolerated. In a Phase 1/2 clinical trial
evaluating BTI-322 for treatment of acute graft-versus-host disease (GvHD) in
bone marrow transplant (BMT) patients unresponsive to steroid therapy, the
compound was well tolerated and 55 percent of the patients responded
positively to treatment, with either a complete response or a reduction in
grade of GvHD. A Phase 1/2 trial has been completed for the prevention of
acute renal transplant rejection in which BTI-322 was given at the time of
organ transplantation. Results of the trial suggested a 58 percent reduction
at two years post-transplant in the incidence of kidney graft rejection
episodes compared to conventional triple drug therapy alone. Two additional
Phase 1/2 clinical trials have been developed to evaluate MEDI-507 as
treatment for acute GvHD in steroid-naive adults and in pediatric patients.
MedImmune has also initiated Phase 1 studies in psoriasis, an autoimmune
disease.
Both MEDI-507 and BTI-322 bind specifically to the CD2 receptor found on T
cells and natural killer (NK) cells. Previous in vitro studies have suggested
that MEDI-507 has the ability to inhibit selectively the response of T cells
directed at transplant antigens, while subsequently allowing immune cells to
respond normally to other antigens. BTI-322 was initially discovered by Drs.
Herve Bazin and Dominique Latinne at the Experimental Immunology Unit of the
Catholic University of Louvain in Belgium.
BioTransplant Incorporated utilizes its proprietary technologies in re-
educating the body's immune responses to allow tolerance of foreign cells,
tissues and organs. Based on this technology, the Company is developing a
portfolio of products designed to treat a range of medical conditions,
including organ and tissue transplantation, cancer and autoimmune disease, for
which current therapies are inadequate. BioTransplant's products are intended
to induce long-term functional transplantation tolerance in humans, increase
the therapeutic benefit of bone marrow transplants, and reduce or eliminate
the need for lifelong immunosuppressive therapy. MedImmune is developing
MEDI-507 under license from BioTransplant, and BioTransplant has retained the
right to use BTI-322 and/or MEDI-507 in its proprietary ImmunoCognance(TM)
systems, which are designed to re-educate the immune system to accept foreign
tissue: the AlloMune(TM) System for human-to-human transplantation, and the
XenoMune(TM) System for porcine-to-human transplantation.
MedImmune, a biotechnology company located in Gaithersburg, Maryland, is
focused on developing and marketing products that address medical needs in
areas such as infectious disease, transplantation medicine, autoimmune
disorders and cancer. The Company currently markets Synagis(R) (palivizumab),
RespiGam(R) (Respiratory Syncytial Virus Immune Globulin Intravenous (Human)),
and CytoGam(R) (Cytomegalovirus Immune Globulin Intravenous (Human)) through
its hospital-based sales force and has five new product candidates in clinical
trials. In October 1995, MedImmune and BioTransplant established a strategic
alliance for development of BTI-322 and any future generation products, such
as MEDI-507, for use in organ transplantation and other indications.
This announcement may contain, in addition to historical information,
certain forward-looking statements that involve risks and uncertainties. Such
statements reflect management's current views and are based on certain
assumptions. Actual results could differ materially from those currently
anticipated as a result of a number of factors, including risks and
uncertainties discussed in both companies' filings with the U.S. Securities
and Exchange Commission.
SOURCE MedImmune, Inc. |
