Healthcare Industry News: GI GVHD
News Release - November 7, 2006
DOR BioPharma Submits European Marketing Application for orBec(R) to Treat GI Graft-Versus-Host Disease
orBec(R) Is First Directed Therapy for GI GVHDMIAMI, FL--(Healthcare Sales & Marketing Network)--Nov 7, 2006 -- DOR BioPharma, Inc. (OTC BB:DORB.OB ) ("DOR" or the "Company") announced today that it has submitted a Marketing Authorization Application ("MAA") to the European Medicines Evaluation Agency ("EMEA") to market orBec® (oral beclomethasone dipropionate) for the treatment of gastrointestinal Graft-versus-Host disease ("GI GVHD"), the most common life-threatening complication of allogeneic hematopoietic stem cell transplantation in cancer patients. The MAA will be reviewed under the centralized licensing procedure, which, if approval is granted, provides a marketing license valid in all 25 member states of the European Union. Review of the application will be coordinated by the EMEA.
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 U.S., but rather are used off-label as investigational therapies for this indication.
The data provided in the MAA submission demonstrate that orBec® safely provides a higher rate of survival when compared with the current standard of care, and a lowered exposure to systemic corticosteroids following allogeneic transplantation. 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 MAA filing is supported by data from two randomized, double-blinded, placebo-controlled clinical trials. The first trial was a 129-patient pivotal Phase III multi-center clinical trial of orBec® conducted at 16 leading bone marrow/stem cell transplant centers in the U.S. and France. The second trial was a 60-patient Phase II single-center clinical trial conducted at the Fred Hutchinson Cancer Institute. Although orBec® did not achieve statistical significance in the primary endpoint of its pivotal trial, namely time to treatment failure through Day 50 (p-value 0.1177), orBec® did achieve statistical significance in other key outcomes such as median time to treatment failure through Day 80 (p-value 0.0226) and, most importantly, demonstrated a statistically significant long-term survival advantage compared with placebo.
In the pivotal Phase III trial, analysis of patient survival at the pre-specified endpoint of 200 days post-transplant showed a clinically meaningful and statistically significant 66% reduction (p-value 0.0139) in mortality among patients randomized to orBec®. The mortality benefit in favor of orBec® was corroborated earlier this year in a retrospective analysis of the Phase II study, which found a 55% reduction in the risk of mortality at 200 days post-transplant. At one year after randomization, there were relatively consistent 51% and 45% reductions in the risk of mortality among patients randomized to orBec® in both the Phase III and Phase II studies, respectively. In the pivotal Phase III trial, a subgroup analysis also revealed that patients dosed with orBec® who had received stem cells from unrelated donors had a 94% reduction in the risk of mortality 200 days post-transplant.
These data were reported in January 2006 at the Tandem BMT Meeting of the American Society for Bone Marrow Transplantation in a poster presentation entitled, "Oral beclomethasone dipropionate for gastrointestinal GVHD: a corticosteroid-sparing treatment with improved survival at day +200. Biology of Blood and Marrow Transplantation 12." The pivotal Phase III study results, as well as the extended mortality results from both trials, have been submitted for publication in a prominent peer-reviewed medical journal.
"The MAA for orBec® represents our first European marketing submission and is an important milestone for DOR," stated Christopher J. Schaber, Ph.D., President and Chief Executive Officer of DOR BioPharma. "We believe that the MAA submission, together with the recent NDA application in the U.S., are high-quality data packages that clearly demonstrate the benefit of orBec® for the treatment of GI GVHD. I am very confident in the positive outcomes our orBec® data have demonstrated. 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 to improve their survival. We look forward to working closely with the EMEA during the review process, and, assuming regulatory approval, to making orBec® available in Europe to GI GVHD patients who desperately need an effective therapy."
Dr. Schaber added, "DOR plans to market orBec® directly to the transplant centers that treat these very sick patients, including the approximately 15 centers responsible for roughly 60% of HSCT procedures in the U.S., and to secure a sales and marketing partner(s) for Europe and the rest of the world."
In addition to issued 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.
George B. McDonald, M.D., Head of the Gastroenterology/Hepatology Section at the Fred Hutchinson Cancer Research Center, inventor of orBec® and a consultant to DOR, stated, "It is often difficult for those not involved in hematopoietic stem cell transplants to understand how devastating the problem of GI GVHD and its limited treatment options can be for patients and their families. Not only are the gastrointestinal symptoms unpleasant and persistent, but the standard treatment using prolonged courses of prednisone often leads to further debility and to serious infections. orBec® treatment controls the symptoms of GI GVHD without the need for prolonged prednisone exposure. I find the data in support of orBec® to be compelling, and look forward to the time when this important new drug can be made available to patients undergoing hematopoietic stem cell transplant."
About Allogeneic Bone Marrow/Stem Stem Cell Transplantation (HSCT)
Allogeneic hematopoietic stem cell transplantation ("HSCT") is considered a potentially curative option for many leukemias as well as other forms of blood cancer. In an allogeneic HSCT 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 HSCT 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 HSCT 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 non-myeloablative 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 HSCT procedures annually in the U.S. 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 HSCT 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 HSCT, however, is GVHD in which the newly transplanted donor cells damage cells in the recipient's gastrointestinal tract, liver and skin.
About Gastrointestinal Graft-versus-Host Disease (GI GVHD)
The gastrointestinal manifestation of GVHD (GI GVHD) occurs in approximately 60% of related donor and 70% of unrelated donor allogeneic transplant patients. Of the organ systems affected by GVHD, GI GVHD is the most common and often the most persistent manifestation of the GVHD process. Symptoms include anorexia, nausea, vomiting, diarrhea, bloody stool, cramping, epithelial cell necrosis and, in severe cases, ulceration and exfoliation of the intestinal mucosa.
GI GVHD patients are often hospitalized if they cannot sustain nutrition from oral intake, in which case they rely on parenteral nutrition for sustenance. Under current standards of care, these patients have a high rate of readmission due to relapse of GI GVHD and the side effects of immunosuppressive therapy that is given to treat GVHD. Infection by cytomegalovirus, adenovirus, bacteria and fungi are particularly common among patients who require prolonged prednisone treatment. These factors contribute to the high rates of hospitalization and mortality in GI GVHD patients.
For more information about allogeneic HSCT and GVHD, please visit the website of the American Society for Blood and Marrow Transplantation at: http://www.bloodline.net/bmtr or visit www.medlineplus.com.
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 1970s 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.
About DOR BioPharma, Inc.
DOR BioPharma, Inc. 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 BioPharma has filed an MAA with the EMEA and an NDA with the FDA for orBec® for the treatment of GI GVHD. orBec® may also have application in treating other gastrointestinal disorders characterized by severe inflammation.
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. The ricin toxin vaccine, RiVax(TM), has successfully completed a Phase I 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 III clinical study (i.e. a p-value of less than or equal to 0.05), 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.
Source: DOR BioPharma
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