DOR BioPharma Announces Positive New Pulmonary Effect Data from orBec Clinical Trials
Abstract and Results to be Presented Today at Annual Tandem Bone Marrow Transplant Conference in San Diego
EWING, NJ - February 13, 2008 - DOR BioPharma, Inc. , a late-stage drug development company, announced today that positive results for orBec® (oral beclomethasone dipropionate or oral BDP) in preventing serious lung injury in patients with gastrointestinal Graft-versus-Host disease (GI GVHD) will be presented this afternoon by Jason W. Chien, MD of the Fred Hutchinson Cancer Research Center (FHCRC) at the annual Tandem Bone Marrow Transplant Meeting of the American Society for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry in San Diego. The presentation is entitled "Preservation of pulmonary diffusing capacity with oral beclomethasone dipropionate: Results from two randomized, placebo-controlled trials in allogeneic graft recipients,"published in Biology of Blood and Marrow Transplantation (Volume 14, Number 2, Supplement 2). DOR is also the Sponsor of the GVHD Working Committee at the conference on Thursday, February 14.
The pulmonary data, collected by DOR in response to a specific FDA request as part of its New Drug Application (NDA) review last summer, included a comparison of patients enrolled at FHCRC in two randomized, double-blind, placebo-controlled clinical trials for the treatment of patients with acute GI GVHD. Sixty patients had been randomized to orBec® and the same number to placebo. Serial Pulmonary Function Tests (PFTs) at day 80 were available from 44 and 50 patients on placebo and orBec®, respectively. Significantly fewer patients randomized to orBec® (55%) had deterioration of pulmonary diffusing capacity by transplant day 80, compared to placebo (79%), p=0.02. Clinical pulmonary events from the time of randomization to 200 days afterwards were reviewed by Dr. Chien of the FHCRC Pulmonary and Critical Care Medicine Section while blinded to the randomization assignment; no patient randomized to orBec® developed a non-infectious pulmonary problem during this interval, compared to 4 patients on placebo.
These data suggest that orBec® (oral BDP) may have a protective effect on early decline in pulmonary diffusing capacity, which commonly occurs by day 80 after transplant because of interstitial lung injury, and that this effect is accompanied by prevention of clinical pulmonary events such as Idiopathic Pneumonia Syndrome and Bronchiolitis Obliterans. It is hypothesized that these beneficial effects on the lungs were due to delivery of the potent immunosuppressive 17-BMP (an active metabolite of BDP) to the lungs via GI mucosa, portal vein, and pulmonary artery.
"The observations presented today in San Diego are intriguing and may lead to the development of new applications of oral BDP in a host of pulmonary inflammatory disorders having significant market opportunity beyond the GI area where we are currently in late-stage development," said Christopher J. Schaber, PhD, President and Chief Executive Officer of DOR. "We will continue to secure intellectual property in this new arena and to begin evaluating the possibilities for future clinical development."
George B. McDonald, MD, Head of the Gastroenterology/Hepatology Section at the FHCRC, inventor of orBec® and an expert medical advisor to DOR, stated, "When we reviewed adverse event data from the pivotal Phase 3 trial of orBec® for treatment of GI GVHD following hematopoietic cell transplantation, we noted a complete absence of non-infectious pulmonary infiltrates in patients in the orBec® arm, compared to 18% in the placebo arm. These infiltrates are caused by inflammation of the lungs, most likely from the donor's immune cells. This observation led to the hypothesis that orBec® (oral BDP), through its potent metabolite 17-beclomethasone monopropionate (17-BMP), delivered to the pulmonary artery via the gut and portal circulation, preserves lung function after allogeneic transplantation. Data presented at the Tandem Bone Marrow Transplant meeting suggests that this hypothesis is true, as significantly fewer orBec® patients from a 120 randomized, single-center patient cohort had deterioration of pulmonary diffusing capacity by transplant day 80 compared to placebo, and none of 60 orBec® patients had a non-infectious pulmonary event during a 200-day observation period, compared to 4 of 60 patients in the placebo arm. These non-infectious pulmonary events are significant causes of mortality after transplantation."
Dr. McDonald continued, "While the dominant effect of oral BDP is in the gastrointestinal mucosa, where it is significantly more effective than placebo in treating GVHD, some of its active metabolite, 17-BMP, reaches the pulmonary vasculature before being cleared from the systemic circulation. Thus, oral BDPmay prevent pulmonary interstitial inflammation and subsequent lung injury. This beneficial effect of BDPcould be useful not only in the setting of allogeneic hematopoietic cell transplantation, but as a potential treatment for a long list of pulmonary inflammatory conditions for which effective treatments are lacking."
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.
Two prior randomized, double-blinded, placebo-controlled Phase 2 and 3 clinical trials demonstrate that orBec® provides clinically meaningful outcomes when compared with the current standard of care, including a lowered exposure to systemic corticosteroids following allogeneic transplantation. Currently, there are no approved products to treat GI GVHD. The first trial was a 60-patient Phase 2 single-center clinical trial conducted at the Fred Hutchinson Cancer Research Center. The second 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. 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 free of GVHD at Day 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).
In the Phase 2 study, the primary endpoint was the clinically relevant determination of whether GI GVHD patients at Day 30 had a durable GVHD treatment response as measured by whether or not they were able to consume at least 70% of their daily caloric intake by mouth. The GVHD 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 GVHD 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 DOR BioPharma
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, or BDP), is a potent, locally acting corticosteroid being developed for the treatment of gastrointestinal Graft-versus-Host disease (GI GVHD), a common and potentially life-threatening complication of bone marrow transplantation. DOR filed a New Drug Application for orBec® with the FDA for the treatment of acute GI GVHD and received a not approvable letter in which the FDA has requested data from an additional clinical trial to demonstrate the safety and efficacy of orBec®. A Marketing Authorization Application with the European Medicines Evaluation Agency has also been validated and is under review. orBec® is currently the subject of an NIH-supported, Phase 2, randomized, double-blind, placebo-controlled trial in the prevention of acute GVHD. Oral BDP may also have application in treating other gastrointestinal disorders characterized by severe inflammation. DOR has initiated a development program with its Lipid Polymer Micelle (LPM(TM)) 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 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, RiVaxTM, has been shown to be well tolerated and immunogenic in a Phase 1 clinical trial in normal volunteers.
For further information regarding DOR BioPharma, Inc., please visit the Company's website located at www.dorbiopharma.com [http://rs6.net/tn.jsp?e=001G0YyT9HWFlm5j0pHRy9rLuaLibOA3LQ5L_Srsvevy80s4pinw6p-F-HgFA5Xg3s2O4e1CMw2jyX1_wEnpu_nbmMujZy1fsSn4FRsfZ2Tja4iWEQ34Eny9Q==].
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 US Government or other countries, that the US 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: the FDA's requirement that DOR conduct additional clinical trials to demonstrate the safety and efficacy of orBec® will take a significant amount of time and money to complete and positive results leading to regulatory approval cannot be assumed; 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; orBec® may not gain market acceptance if it is eventually approved by the FDA; 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
Posted: February 2008