DOR Biopharma's investigational gastrointestinal Graft-versus-Host disease treatment orBec (oral beclomethasone dipropionate) did not reach statistical significance in its primary endpoint of time to treatment failure through day 50 in a pivotal Phase III trial, the company told analysts Jan. 25.

Results of the study along with analysis of an earlier Phase II study were published online Jan. 23 in Blood, a journal of the American Society of Hematology.

Miami-based DOR's NDA for orBec, a two-pill product designed to release BDP in the upper and then lower GI tract, has a July 21 user-fee date.

During the call, the lead researcher on the project, George McDonald (Fred Hutchinson Cancer Research Center, Seattle) blamed the failure of the treatment to show statistical significance at day 50 on the high-dose prednisone used in the induction phase of the study.

The goal of the study was to first control the inflammatory process caused by GVHD with an induction course of prednisone, then taper the prednisone and maintain control with beclomethasone for 40 additional days, McDonald said.

"The failure to meet the primary endpoint is quite clearly related to the failure rate to prednisone, not the failure rate to the orBec," McDonald said. "Forty-four percent of the patients in the beclomethasone arm who had treatment failure over the entire study had it happen in the first 10 days when they were on high-dose prednisone."

Other endpoints for which orBec did achieve statistical significance were reduction in the risk of treatment through day 80 and long-term survival compared with placebo. "By day 200 post-transplant, five patients randomized to BDP had died, compared to 16 deaths on placebo, a 67 percent reduction in the hazard of mortality," the Blood article states.

Long-term follow-up from the 1998 Phase II study showed that "at a median of three and a half years after randomization, there was a 37 percent reduction in the hazard of death," McDonald added.

"The volume of ... evidence is really quite clinically persuasive. That's why I presume Blood accepted the paper," he said.

The CEO of Seattle-based Cell Therapeutics agrees with McDonald's assessment. CTI, which has a background in bone marrow transplantation, made a bid to buy DOR earlier this month.

"It's not going to be a shoe-in at the FDA ... it's going to have to be a clinical benefit argument that ... will carry the day," CTI CEO James Bianco commented to "The Pink Sheet" DAILY.

If DOR has to go before FDA's Oncology Drugs Advisory Committee, "I think the ODAC clinicians will see the benefits and would likely recommend the approval, That's why we took the chance on the offer," Bianco said.

[Editor's note: An interview with Cell Therapeutics CEO James Bianco will appear in the next issue of "The Pink Sheet" DAILY.]

Other companies operating in the GVHD space include Baltimore-based Osiris Therapeutics. The adult stem cell company is evaluating Prochymal , mesenchymal stem cells that act as an immunomodulator, in steroid-refractory acute GVHD.

Xoma, based in Berkeley, Calif., is developing Neuprex (opebacan), a "host defense" protein that currently is in an open label, dose-escalating Phase I/II clinical study for adults and children undergoing allogeneic hematopoietic stem cell transplantation.

With its November acquisition of AnorMed, Cambridge, Mass.-based Genzyme gained the Phase III HSCT candidate Mozobil (plerixafor), a CXCR4 chemokine receptor agonist that has been shown to increase the number of stem cells in circulation in the blood (¹ Also see "Genzyme Wins AnorMED As Millennium Backs Out Of Bidding War" - Pink Sheet, 18 October, 2006.).

In September, Schering-Plough's Noxafil (posaconazole) became the first antifungal approved for prevention of invasive Aspergillus infections. Indications include prophylaxis in severely immunocompromised HSCT patients with GVHD (² Also see "Noxafil Is First FDA-Approved Antifungal For Aspergillus Infection Prevention" - Pink Sheet, 19 September, 2006.).

-Shirley Haley (s.haley@elsevier.com)

DOR Biopharma’s orBec For GI Disease Misses Primary Endpoint

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