EWING, NJ -- 10/09/07 --
DOR BioPharma, Inc. (OTCBB: DORB) (DOR or the
Company) announced that a summary of all clinical trials to date of its
drug orBec® (oral beclomethasone dipropionate, or oral BDP) in the
treatment of gastrointestinal Graft-versus-Host disease (GI GVHD) has been
published in the peer-reviewed medical journal Expert Opinion on
Investigational Drugs. The publication "Oral Beclomethasone Dipropionate,
a Topically-Active Corticosteroid for Treatment of Gastrointestinal
Graft-vs.-Host-Disease Following Allogeneic Hematopoietic Cell
Transplantation," is authored by George B. McDonald, MD, inventor of
orBec® and Head of the Gastroenterology/Hepatology Section at the Fred
Hutchinson Cancer Research Center, located in Seattle, Washington. The
full article is available online at
http://www.expertopin.com/doi/abs/10.1517/13543784.16.10.1709.
Expert Opinion on Investigational Drugs is a monthly peer-reviewed journal,
evaluating developments in pharmaceutical research, from animal studies to
the launch of a new medicine. Authors are encouraged to express their
Expert Opinion of the status of the research under review, rather than
simply review the available data. The audience consists of scientists,
managers and decision-makers in the pharmaceutical industry, and others
closely involved in R&D. Expert Opinion on Investigational Drugs adopts a
systematic approach to coverage, with each issue focusing on one of the
major therapeutic areas.
The Expert Opinion paper concludes that two randomized, double-blinded
placebo-controlled trials have demonstrated that orBec®, formulated as
gastric-release and enteric coated pills and dosed at 8 mg/day, is safe and
effective in treating acute GI GVHD when used in conjunction with a 10 day
induction course of prednisone. In the pivotal Phase 3 trial, among
patients eligible for prednisone taper after 10 days of induction therapy,
treatment with oral BDP reduces the risk of GVHD treatment failure at study
days 50 and 80 by over 60%. The type of pre-transplant conditioning and
donor had no impact on the frequency of GVHD treatment failure during the
80-day study period. Both randomized trials demonstrated a 45% reduction in
the risk of mortality one year after randomization, due in large part to a
reduction in death due to infection and recurrent hematologic malignancy,
with the greatest benefit in terms of survival among patients who had
received non-myeloablative conditioning therapy and among those who
received a graft from other than an HLA-matched sibling. Oral BDP is the
only therapy studied in the last 30 years to effectively treat acute GVHD
and reduce mortality.
Dr McDonald's opinion is that the use of orBec® in treating the
pan-intestinal inflammation of acute GVHD substitutes a well characterized,
topically active glucocorticoid with limited systemic bioavailability, less
toxicity, and an extensive safety history, for high-dose prednisone, which
is a systemic immune suppressant with a multitude of side effects,
particularly a predisposition to infections, both opportunistic and
routine. The same strategy has been used effectively in treating other
inflammatory disorders such as acute attacks of asthma, where an induction
course of prednisone to control the acute process is followed by topical,
inhaled corticosteroids, including BDP.
"This is the second recent publication of our data in a well regarded
peer-reviewed journal," stated Christopher J. Schaber, PhD, President and
Chief Executive Officer of DOR BioPharma. "We are pleased with the exposure
orBec® has been getting in the medical community as a result of these
publications. Two randomized trials have shown that orBec® prevents
relapses of acute GI GVHD, with an effect that has been shown to be durable
even following discontinuation of therapy. We believe that orBec®, if
approved, will potentially provide transplant physicians with an effective
and much needed tool to treat their GI GVHD patients and improve outcomes
including survival. We will continue working with the FDA and EMEA toward
potential regulatory approval".
About the orBec® NDA
The data included in the NDA submission indicate that orBec® may provide
clinical benefit when compared with the current standard of care, including
a lowered exposure to systemic corticosteroids following allogeneic
hematopoietic cell transplant. Currently there are no approved products to
treat GI GVHD. Thus an approval of orBec® would represent the first
directed therapy for GI GVHD.
The NDA filing is supported by data from two randomized, double-blinded,
placebo-controlled clinical trials. The first trial was a 129-patient
pivotal Phase 3 multi-center clinical trial of orBec® conducted at 16
leading bone marrow/stem cell transplantation centers in the US and
France. The second trial was a 60-patient Phase 2 single-center clinical
trial conducted at the Fred Hutchinson Cancer Research Center. Although
orBec® did not achieve statistical significance in the primary endpoint
of its pivotal trial, namely median time to treatment failure through Day
50 (p-value 0.1177), orBec® did achieve statistical significance in other
key secondary endpoints such as the proportion of patients who were
treatment failures at study days 50 and 80 and the median time to treatment
failure through Day 80 (p-value 0.0226), as well as a 66% reduction in
mortality among patients randomized to orBec® at 200 days post-transplant
with only 5 patient (8%) deaths in the orBec® group compared to 16
patient (24%) deaths in the placebo group (p-value 0.0139). At one year
post-randomization in the pivotal Phase 3 trial, 18 patients (29%) in the
orBec® group and 28 patients (42%) in the placebo group died within one
year of randomization (46% reduction in mortality, hazard ratio 0.54, 95%
CI: 0.30, 0.99, p=0.04, stratified log-rank test).
The frequencies of severe adverse events, adverse events related to study
drug, and adverse events resulting in study drug discontinuation were all
comparable to that of the placebo group in both trials. Patients who
remained on orBec® until Day 50 in the pivotal study had a higher
likelihood of having biochemical evidence of abnormal HPA function compared
to patients on placebo.
In the Phase 2 study, the primary endpoint was the clinically relevant
determination of whether GI GVHD patients at Day 30 were or were not able
to consume at least 70% of their daily caloric intake by mouth, as compared
to intravenous parenteral nutrition administered in the hospital. The
treatment response at Day 30 was 22 of 31 (71%) vs. 12 of 29 (41%) in the
orBec® and placebo groups respectively, achieving a statistically
significant p-value of 0.02. Additionally, the treatment response at Day
40 was 16 of 31 (52%) vs. 5 of 29 (17%) in the orBec® and placebo groups
respectively, achieving a statistically significant p-value of 0.007.
About GI GVHD
GVHD is a debilitating and painful disease. It is a common disorder among
immunocompromised cancer patients after receiving allogeneic stem cell or
bone marrow transplants. Unlike organ transplantation where the patient's
body may reject the organ, in GVHD it is the donor cells that begin to
attack the patient's body -- most frequently the gut, liver and skin.
Patients with mild-to-moderate GI GVHD typically develop symptoms of
anorexia, nausea, vomiting and diarrhea. If left untreated, GI GVHD can
progress to ulcerations in the lining of the GI tract, and in its most
severe form, can be fatal.
OrBec® is a two-tablet system containing the highly potent, topically
active corticosteroid beclomethasone dipropionate, and is designed to
specifically target and treat upper and lower GI GVHD with reduced systemic
immunosuppressive side effects. Systemic immunosuppressive agents such as
prednisone, which are the current standard treatments for GI GVHD, are
associated with high mortality rates due to infection and debility.
Further, these drugs have not been approved for treating GI GVHD in the
European Union or in the US, but rather are used off-label as
investigational therapies for this indication.
About Allogeneic HCT
Allogeneic hematopoietic cell transplantation (HCT) is considered a
potentially curative option for many leukemias as well as other forms of
blood cancer. In an allogeneic HCT procedure, hematopoietic stem cells are
harvested from a closely matched relative or unrelated person, and are
transplanted into the patient following either high-dose chemotherapy or
intense immunosuppressive conditioning therapy. The curative potential of
allogeneic HCT is now partly attributed to the so-called
graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects of the
newly transplanted donor cells to recognize and destroy malignant cells in
the recipient patient.
The use of allogeneic HCT has grown substantially over the last decade due
to advances in human immunogenetics, the establishment of unrelated donor
programs, the use of cord blood as a source of hematopoietic stem cells and
the advent of reduced intensity conditioning regimens ("mini-transplants")
that avoid the side effects of high-dose chemotherapy. Based on the latest
statistics available, it is estimated that there are more than 10,000 HCT
procedures annually in the US and a comparable number in Europe. Estimates
as to the current annual rate of increase in these procedures are as high
as 20%. High rates of morbidity and mortality occur in this patient
population. Clinical trials are also underway testing allogeneic HCT for
treatment of some metastatic solid tumors such as breast cancer, renal cell
carcinoma, melanoma and ovarian cancer. Allogeneic transplants have also
been used as curative therapy for several genetic disorders, including
immunodeficiency syndromes, inborn errors of metabolism, thalassemia and
sickle cell disease. The primary toxicity of allogeneic HCT, however, is
GVHD in which the newly transplanted donor cells damage cells in the
recipient's gastrointestinal tract, liver and skin.
About orBec®
OrBec® represents a first-of-its-kind oral, locally acting therapy
tailored to treat the gastrointestinal manifestation of GVHD, the organ
system where GVHD is most frequently encountered and highly problematic.
OrBec®, if approved by the EMEA and the FDA, would be the first oral
formulation of beclomethasone dipropionate ("BDP") available in the
European Union and the United States, respectively. OrBec® is intended
to reduce the need for systemic immunosuppressive drugs to treat GI GVHD.
BDP is a highly potent, topically active corticosteroid that has a local
effect on inflamed tissue. BDP has been marketed in the U.S. and worldwide
since the early 1970's as the active pharmaceutical ingredient in a nasal
spray and in a metered-dose inhaler for the treatment of patients with
allergic rhinitis and asthma. OrBec® is formulated for oral
administration as a single product consisting of two tablets; one tablet is
intended to release BDP in the proximal portions of the GI tract and the
other tablet is intended to release BDP in the more distal portions of the
GI tract.
In addition to issued patents and pending worldwide patent applications
held by or exclusively licensed to DOR, orBec® also benefits from orphan
drug designations in the U.S. and in Europe for the treatment of GI GVHD,
which provide for 7 and 10 years of post-approval market exclusivity,
respectively.
About DOR BioPharma, Inc.
DOR BioPharma, Inc. (DOR) is a biopharmaceutical company developing
products to treat life-threatening side effects of cancer treatments and
serious gastrointestinal diseases, and vaccines for certain bioterrorism
agents. DOR's lead product, orBec® (oral beclomethasone dipropionate), is
a potent, locally acting corticosteroid being developed for the treatment
of GI GVHD, a common and potentially life-threatening complication of bone
marrow transplantation. DOR has filed an NDA for orBec® with the FDA for
the treatment of GI GVHD, and subsequent to supplemental information
recently submitted, the FDA has extended the PDUFA (Prescription Drug User
Fee Act) date to October 21, 2007. An MAA (Marketing Authorization
Application) with the EMEA (European Medicines Evaluation Agency) has also
been filed and validated. OrBec® may also have application in treating
other gastrointestinal disorders characterized by severe inflammation. DOR
has recently initiated a development program with its Lipid Polymer Micelle
(LPM(TM)) oral drug delivery technology for the oral delivery of leuprolide
for the treatment of prostate cancer and endometriosis, as well as a
development program with its oral azathioprine technology for the treatment
of oral GVHD.
Through its Biodefense Division, DOR is developing biomedical
countermeasures pursuant to the recently enacted Project BioShield Act of
2004. DOR's biodefense products in development are recombinant subunit
vaccines designed to protect against the lethal effects of exposure to
ricin toxin and botulinum toxin. DOR's ricin toxin vaccine, RiVax(TM), has
been shown to be well tolerated and immunogenic in a Phase 1 clinical trial
in normal volunteers.
For further information regarding DOR BioPharma, please visit the Company's
website located at www.dorbiopharma.com.
This press release contains forward-looking statements, within the meaning
of Section 21E of the Securities Exchange Act of 1934, that reflect DOR
BioPharma, Inc.'s current expectations about its future results,
performance, prospects and opportunities, including statements regarding
the potential use of orBec® for the treatment of gastrointestinal GVHD
and the prospects for regulatory filings for orBec®. Where possible, DOR
has tried to identify these forward-looking statements by using words such
as "anticipates," "believes," "intends," or similar expressions. These
statements are subject to a number of risks, uncertainties and other
factors that could cause actual events or results in future periods to
differ materially from what is expressed in, or implied by, these
statements. DOR cannot assure you that it will be able to successfully
develop or commercialize products based on its technology, including
orBec®, particularly in light of the significant uncertainty inherent in
developing vaccines against bioterror threats, manufacturing and conducting
preclinical and clinical trials of vaccines, and obtaining regulatory
approvals, that its technologies will prove to be safe and effective, that
its cash expenditures will not exceed projected levels, that it will be
able to obtain future financing or funds when needed, that product
development and commercialization efforts will not be reduced or
discontinued due to difficulties or delays in clinical trials or due to
lack of progress or positive results from research and development efforts,
that it will be able to successfully obtain any further grants and awards,
maintain its existing grants which are subject to performance, enter into
any biodefense procurement contracts with the U.S. Government or other
countries, that the U.S. Congress may not pass any legislation that would
provide additional funding for the Project BioShield program, that it will
be able to patent, register or protect its technology from challenge and
products from competition or maintain or expand its license agreements with
its current licensors, or that its business strategy will be successful.
Important factors which may affect the future use of orBec® for
gastrointestinal GVHD include the risks that: because orBec® did not
achieve statistical significance in its primary endpoint in the pivotal
Phase 3 clinical study (i.e. a p-value of less than or equal to 0.05), the
Oncologic Drug Advisory Committee ("ODAC") appointed by the FDA voted that
the data supporting orBec® did not show substantial evidence of efficacy
by a margin of 7 to 2 for the treatment of GI GVHD, although the FDA is not
bound by ODAC's decision, the FDA may not consider orBec® approvable
based upon existing studies, orBec® may not show therapeutic effect or an
acceptable safety profile in future clinical trials, if required, or could
take a significantly longer time to gain regulatory approval than DOR
expects or may never gain approval; DOR is dependent on the expertise,
effort, priorities and contractual obligations of third parties in the
clinical trials, manufacturing, marketing, sales and distribution of its
products; or orBec® may not gain market acceptance; and others may
develop technologies or products superior to orBec®. These and other
factors are described from time to time in filings with the Securities and
Exchange Commission, including, but not limited to, DOR's most recent
reports on Form 10-QSB and Form 10-KSB. DOR assumes no obligation to update
or revise any forward-looking statements as a result of new information,
future events, and changes in circumstances or for any other reason.
Company Contact:
Evan Myrianthopoulos
Chief Financial Officer
(609) 538-8200
www.dorbiopharma.com
