Healthcare Industry News: Medline
News Release - November 21, 2006
FDA Accepts DOR BioPharma's NDA Filing for orBec(R)MIAMI, FL--(Healthcare Sales & Marketing Network)--Nov 21, 2006 -- DOR BioPharma, Inc. (OTC BB:DORB.OB ) ("DOR" or the "Company") announced today that the U.S. Food and Drug Administration ("FDA") has accepted the Company's New Drug Application ("NDA") for orBecŪ (oral beclomethasone dipropionate) for the treatment of gastrointestinal Graft-versus-Host disease ("GI GVHD"). The FDA has granted the orBecŪ NDA application a standard review designation and established a target action date of July 21, 2007 for completion of review of the NDA in accordance with The Prescription Drug User Fee Act ("PDUFA"). The FDA's Acceptance of the filing indicates the FDA has determined that the NDA is sufficiently complete to permit a substantive review.
Christopher J. Schaber, Ph.D., President and Chief Executive Officer of DOR, stated, "We are proud to announce FDA acceptance of our NDA for orBecŪ, which is an important milestone for our company. We believe the data included in this filing clearly demonstrate the clinical benefit of orBecŪ in treating patients suffering from GI GVHD. We are now within sight of a possible approval of orBecŪ, and are looking forward to productive interactions with the FDA."
GI GVHD is the most common life-threatening complication of allogeneic hematopoetic stem cell transplantation ("HSCT"). Currently, there are no FDA approved treatments for GI GVHD, rendering this often fatal disease an area of unmet medical need. orBecŪ is a two-pill system containing the highly potent, topically active corticosteroid, beclomethasone dipropionate, designed to specifically target and treat upper and lower GI GVHD with reduced systemic immunosuppressive side effects. Although not approved by the FDA for this indication, systemic immunosuppressive agents, such as prednisone, are currently the standard treatment for GI GVHD despite being associated with high rates of mortality due to infection and debility.
The data provided in the NDA submission demonstrate that orBecŪ safely provides a lower risk of mortality compared with the current standard of care, and a lower exposure to systemic corticosteroids following allogeneic HSCT transplantation. The NDA filing is supported by data from two randomized, double-blinded, placebo-controlled clinical trials. The first was a 129 patient pivotal Phase 3 clinical trial for orBecŪ conducted at 16 bone marrow/stem cell transplant centers in the U.S. and France. The second trial was a 60 patient Phase 2 clinical trial conducted at the Fred Hutchinson Cancer Research Center. While orBecŪ 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), orBecŪ 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, it demonstrated a statistically significant survival advantage in comparison to placebo. In the pivotal Phase 3 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 orBecŪ. The mortality benefit in favor of orBecŪ was corroborated earlier this year in a retrospective analysis of the Phase 2 study in which there was a 55% reduction in 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 orBecŪ in both the Phase 3 and Phase 2 studies, respectively. In the pivotal Phase 3 trial, a subgroup analysis also revealed that patients dosed with orBecŪ who had received stem cells from unrelated donors had a 94% reduction in the risk of mortality at Day 200.
"There are more than 10,000 allogeneic stem cell transplants in the U.S. each year," added Dr. Schaber. "It is estimated that allogeneic transplants will increase by as much as 20% annually over the next several years, with cord-blood and reduced intensity conditioning regimens, known as 'mini-transplants,' in the elderly fueling much of this growth. Unfortunately, more than half of these patients will go on to develop GI GVHD that requires treatment. We believe that orBecŪ, if approved, will potentially provide transplant physicians with an effective and much-needed tool to treat their GI GVHD patients and to improve survival. If approved, it is our intention to commercialize orBecŪ on our own in the United States, and to partner it in Europe and the rest of the world."
DOR filed a Marketing Authorization Application (MAA) via the centralized procedure with the European Medicines Agency (EMEA) on November 7, 2006 for orBec for the treatment of GI GVHD. orBecŪ has been granted orphan drug status by the EMEA which provides for ten (10) years of marketing exclusivity in European member countries.
About Allogeneic Bone Marrow/Hematopoietic Stem Cell Transplantation (HSCT)
Allogeneic hematopoietic stem cell transplantation ("HSCT") is considered a potentially curative option for many leukemias as well as for 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. 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.
orBecŪ 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 is highly problematic. orBecŪ, 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. orBecŪ 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. orBecŪ 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, orBecŪ (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 with the FDA for the treatment of GI GVHD, and has received an FDA PDUFA date of July 21, 2007. An MAA with the EMEA for orBecŪ has also been filed. orBecŪ 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, RiVaxTM, has successfully completed 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 orBecŪ for the treatment of gastrointestinal GVHD and the prospects for regulatory filings for orBecŪ. 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 orBecŪ, 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 orBecŪ for gastrointestinal GVHD include the risks that: because orBecŪ 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 FDA may not consider orBecŪ approvable based upon existing studies, orBecŪ 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 orBecŪ may not gain market acceptance; and others may develop technologies or products superior to orBecŪ. 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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