Pharmos Presents New Analysis of Phase II Head Trauma Trial Positive Results Obtained from Orientation and Amnesia Test
ISELIN, N.J., Sept. 27 /PRNewswire/ -- Pharmos Corporation (Nasdaq: PARS; Easdaq: PHRM) is presenting today at the annual meeting of the Congress of Neurological Surgeons in San Antonio, Texas the results of a new analysis recently completed on its Phase II escalating-dose clinical trial of dexanabinol in severe traumatic brain injury (TBI). The results demonstrated that dexanabinol significantly improved orientation and memory among conscious patients, reduced 10-day brain related mortality by 50% and significantly prevented the elevation of intracranial pressure (ICP).
``Dexanabinol established a safety profile and a trend of efficacy in severe TBI. This is very encouraging and strongly supports a Phase III study,'' said Lawrence F. Marshall, M.D., Professor and Chair of the Division of Neurological Surgery at the University of California, San Diego Medical Center, and recognized opinion leader regarding TBI.
An analysis of patient performance on the Galveston Orientation and Amnesia Test (GOAT) demonstrated significantly better results in the dexanabinol treated patients at 1, 3 and 6 months follow-up compared to placebo. GOAT is a neurological test that measures awareness of surroundings and ability to remember. While 6 month outcome as measured by the Glasgow Outcome Scale (GOS) was similar in the treated and placebo groups as a whole, a comparison of outcome within the subgroup of very severe (Glasgow Coma Scale ``GCS'' 4-6) patients revealed a more than two-fold increase in the percentage of those achieving good recovery (28.0% in the dexanabinol group vs. 11.7% in the placebo group). In addition, neurological recovery appeared to be accelerated in the dexanabinol treated group, such that the percentage of dexanabinol patients achieving good recovery (measured by GOS) at 1 month was significantly higher than in the placebo group (17% vs. 2%, p less than 0.02).
Despite the fact that the drug treated groups contained a larger number of more severely injured patients, an analysis of the adverse medical events during the first 10 days post-treatment revealed trends of a lower incidence (p less than 0.2) of mortality (3 vs. 6 patients, or 5.8% vs. 12.2%), fever (88% vs. 98%) and hypotension (19% vs. 33%) in the dexanabinol treated group compared to placebo. (Three more patients in the dexanabinol treated group and one more in the placebo group died later of peripheral complications from other injuries sustained at the time of the brain injury, bringing the total to 6 deaths in the test group, or 11.5%, and 7 deaths in the placebo group, or 14.3%.) ICP management was significantly improved in the dexanabinol group without concomitant reductions in systolic blood pressure. Thus, the mean percentage time with ICP above 25mmHg, a highly negative prognostic factor, was reduced by 60-80% on Days 1-4 post-injury in the dexanabinol treated group compared to placebo. The difference was highly significant (p less than 0.01) on Day 2.
``I am very pleased with the results of the study'', said Dr. Haim Aviv, Chairman and CEO, ``This analysis underscores our belief that dexanabinol has the potential to become a very important product for the treatment of severe TBI.''
Pharmos tested three dose levels of dexanabinol in its Phase II study. Results of the first two doses, 48 mg. and 150 mg., were reported previously. The Company completed testing of a third dose level, 200 mg., in January 2000, and reported initial results of this cohort earlier this year. The full study enrolled a total of 101 patients (dexanabinol: N=52, placebo: N=49) with severe TBI (GCS 4-8) in 6 neurotrauma centers in Israel, following approval of the protocol by the institutional review boards and the Ministry of Health. The drug or placebo (vehicle) was administered as a single intravenous dose within six hours of injury. Hemodynamic parameters, ICP and cerebral perfusion pressure were continuously monitored over the first three days in the ICU. Adverse medical events, clinical laboratory parameters and neurological outcome were evaluated at 10 days and at one, three and six months post-injury.
Overall, the demographics of the patients were those characteristic of the TBI population, mostly young (mean age 30), mostly men (greater than 80%) with motor vehicle accidents as the leading cause (70%) of injury. The injury severity as reflected by the GCS score and the CT scan was weighted towards the less severe end of the spectrum, with a median GCS score of seven. Randomization was adequate in the first two dose groups. In the third cohort, the drug group had significantly more high-risk patients with more severe injuries compared to the related placebo group. Combining all drug-treated patients separately from all placebo patients in an intent-to-treat statistical comparison, there were no statistically significant differences in demographics and baseline characteristics between the groups. However, the median motor response (four in the dexanabinol group as compared to five in the placebo group) and CT classification demonstrated a trend towards more severe injuries in the dexanabinol treated group.
The results of the study enabled the refinement of the protocol for the international pivotal TBI clinical trial, which is scheduled to commence in Europe this year. Logistical efforts by Pharmos and Quintiles, and the submission of regulatory documents in seven European countries and in Israel, are ongoing. |
