Healthcare Industry News: RiVax
News Release - October 9, 2007
orBec(R) Clinical Summary Published in "Expert Opinion on Investigational Drugs"EWING, NJ--(Healthcare Sales & Marketing Network)--Oct 9, 2007 -- DOR BioPharma, Inc. (OTC BB:DORB.OB ) (DOR or the Company) announced that a summary of all clinical trials to date of its drug orBecŪ (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 orBecŪ 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/10.1517/13543718.104.22.1689.
The Expert Opinion paper concludes that two randomized, double-blinded placebo-controlled trials have demonstrated that orBecŪ, 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 orBecŪ 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 orBecŪ has been getting in the medical community as a result of these publications. Two randomized trials have shown that orBecŪ prevents relapses of acute GI GVHD, with an effect that has been shown to be durable even following discontinuation of therapy. 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 improve outcomes including survival. We will continue working with the FDA and EMEA toward potential regulatory approval".
About the orBecŪ NDA
The data included in the NDA submission indicate that orBecŪ 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 orBecŪ 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 orBecŪ 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 orBecŪ 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), orBecŪ 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 orBecŪ at 200 days post-transplant with only 5 patient (8%) deaths in the orBecŪ 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 orBecŪ 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 orBecŪ 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 orBecŪ 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 orBecŪ 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.
OrBecŪ 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.
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 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 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. 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.
In addition to issued patents and pending worldwide patent applications held by or exclusively licensed to DOR, orBecŪ 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, 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 for orBecŪ 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. OrBecŪ 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 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 Oncologic Drug Advisory Committee ("ODAC") appointed by the FDA voted that the data supporting orBecŪ 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 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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