orBecTreatment for Intestinal Graft-versus-Host Disease (iGVHD)
DOR BioPharma Announces Results of orBec End of Review Conference with the FDA
EWING, NJ, December 7, 2007 -- DOR BioPharma, Inc. today reported the results of its recent End of Review Conference with the Food and Drug Administration (FDA) for the orBec New Drug Application (NDA). The purpose of the meeting was to gain further clarification regarding the deficiencies noted in the October 18, 2007 not approvable letter and the data required to gain approval for orBec for the treatment of gastrointestinal Graft-versus-Host disease (GI GVHD).
A summary of the important results of the FDA meeting are as follows:
1. A single, confirmatory, Phase 3 clinical trial could provide sufficient evidence of efficacy provided that it is well designed, well executed and provides clinically and statistically meaningful findings.
2. DOR anticipates working quickly with the FDA to finalize the design of the confirmatory trial and will be requesting a Special Protocol Assessment (SPA) meeting in the near future.
3. The FDA would be agreeable to reviewing a plan for a Treatment IND as long as it does not interfere with patient accrual in a confirmatory trial, such as potentially enrolling patients that would not be eligible for the Phase 3 study.
"Our recent meeting with the FDA was a productive one. We are pleased to have clarification on clinical issues resulting from our recent PDUFA letter," stated Christopher J. Schaber, PhD, President and CEO of DOR BioPharma. "Once we obtain agreement from the FDA on the design of the next clinical trial, we will be able to provide guidance on trial size and timeline and also anticipate being able to begin designing a plan for the Treatment IND. Given the pharmacology and clinically important data orBec has already demonstrated in Phase 2 and 3 clinical trials, both DOR and its clinical investigators are eager to move forward as quickly as possible."
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 transplant 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 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 treatment response as measured by whether or not they were 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 transplants 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.
Systemic immunosuppressive agents such as prednisone are the current standard treatments for GI GVHD and are associated with high mortality rates due to infection and debility. Further, these drugs have not been approved for treating GI GVHD in the US or European Union, but rather are used off-label as investigational therapies for this indication.
About Treatment INDs/Protocols
Treatment protocols and treatment INDs are intended to facilitate the availability of promising new drugs to desperately ill patients as early in the drug development process as possible, before general marketing begins, and to obtain additional data on the drug's safety and effectiveness. FDA permits an investigational drug to be used for a treatment use under a treatment protocol or treatment IND if:
(i) the drug is intended to treat a serious or immediately life-threatening disease;
(ii) there is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease in the intended patient population;
(iii) the drug is under investigation in a controlled clinical trial under an IND in effect for the trial, or all clinical trials have been completed; and
(iv) the sponsor of the controlled clinical trial is actively pursuing marketing approval of the investigational drug with due diligence.
Along with a treatment IND or treatment protocol, the sponsor has the opportunity to recoup some of the costs associated with execution of the treatment protocol via charging for the investigational drug. FDA must be notified in writing in advance of commencing any such charges. Authorization for charging goes into effect automatically 30 days after receipt by FDA of the information amendment, unless the sponsor is notified to the contrary.
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 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 additional clinical trials 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. orBec may also have application in treating other gastrointestinal disorders characterized by severe inflammation. DOR has initiated a development program with its Lipid Polymer Micelle (LPMT) 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 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.
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.
Posted: December 2007
- DOR BioPharma Receives Not Approvable Letter From FDA for orBec for Treatment of Gastrointestinal Graft-vs.-Host Disease - October 19, 2007
- DOR BioPharma, Inc. Announces 3 Month Extension of FDA PDUFA Action Date for orBec New Drug Application to Review Supplemental Data - July 19, 2007
- DOR BioPharma Files New Drug Application with FDA to Market orBec for GI GVHD - September 22, 2006
- DOR BioPharma Provides Regulatory Update on orBec - June 30, 2006
- DOR BioPharma Plans FDA NDA and European MAA Filing Strategy for orBec - November 15, 2005
- DOR BioPharma to File NDA for orBec - April 20, 2005