Washington Editor

Investors unloaded their holdings in IDM Pharma Inc. and DOR BioPharma Inc. after the FDA released material ahead of an advisory meeting on both companies' drugs for cancer patients.

Specifically, IDM's stock (NASDAQ:IDMI) plunged $3.88 on Monday, or 43.4 percent, to close at $5.06. DOR's shares (OTC BB:DORB) fell 30 cents, or 42.9 percent, to close at 40 cents.

The FDA's briefing documents conveyed its reviewers' overall dissatisfaction with both companies' new drug applications, and the agency's Oncology Drug Advisory Committee is scheduled to meet Wednesday to further analyze their submissions.

IDM's NDA for Junovan (mifamurtide), which is being developed as a treatment for newly diagnosed, resectable, high-grade osteosarcoma following surgical resection in combination with multi-agent chemotherapy, is based on a single study in about 600 children and young adults. But the FDA said data from the study don't demonstrate that the product provides substantial evidence of efficacy on disease-free survival.

Its reviewers also noted that questions about trial design, data collection and analytic approach might have been rectified if an end-of-Phase II meeting had been held before the study began. There was no such discussion prior to initiation.

The company, of Irvine, Calif., designed the trial to demonstrate superior disease-free survival for Junovan plus standard chemotherapy of cisplatin, methotrexate and doxorubicin over that standard regimen; that a chemotherapy regimen containing ifosfamide results in superior disease-free survival compared to the standard regimen; and to demonstrate superior disease-free survival for the ifosfamide-containing regimen plus Junovan over the standard chemotherapeutic regimen.

But the FDA said the addition of Junovan to standard treatment failed to result in superior disease-free survival compared to the standard regimen alone (p=0.96); the experimental ifosfamide-containing regimen was not superior to the standard regimen and the observed trend suggested poorer disease-free survival (p=0.35); and the ifosfamide-containing regimen plus Junovan was not superior to the standard regimen (p=0.11).

The reviewers also concluded that it's inappropriate to pool results across study arms because of the qualitative differences in effects on disease-free survival when Junovan is added to standard chemotherapy as compared to when it is added to the new chemotherapy regimen, and because the results are driven by comparing the addition of Junovan to a chemotherapy regimen that performed worse than standard chemotherapy.

As for DOR, which submitted an NDA for orBec (oral beclomethasone dipropionate) as a treatment for gastrointestinal graft-vs.-host disease, the agency's briefing document calls the Miami company's conclusions exploratory and hypothesis-generating.

That's because the application relies on post hoc data that weren't designed to be used in such a way, the reviewers said, adding that such additional analyses increase the probability of a false-positive result.

Data underlying DOR's submission, culled from two randomized, double-blind, placebo-controlled trials, demonstrate that the anti-inflammatory corticosteroid might provide a higher rate of survival when compared with the current standard of care, as well as a lowered exposure to systemic corticosteroids following allogeneic transplantation. But the product did not achieve statistical significance in the primary endpoint of its pivotal trial, time to treatment failure through the 50th day (p=0.1177).

However, orBec did achieve statistical significance in other outcomes such as median time to treatment failure through the 80th day (p=0.0226), and demonstrated a statistically significant long-term survival advantage compared with placebo.

But the FDA said DOR's proposal to combine data from the pivotal trial and a supportive study to demonstrate efficacy based on post hoc analysis and endpoints is problematic because of differences between the trials and patient populations. Some of the reviewers' concerns stem from the different primary endpoints and objectives in the two studies, which also had different designs, as well as changes in transplant procedures and supportive care during the 10 years between the start of the supportive study and the completion of the pivotal trial. In addition, the trials had different dosing regimens and schedules.