BioWorld International Correspondent
With positive Phase IIb clinical trial data in hand, D-Pharm Ltd. is looking to move its novel treatment for acute ischemic stroke DP-b99 into a pivotal Phase III clinical trial late this year or early next year.
The Phase IIb study involved 150 patients at 27 centers in Israel, Germany and South Africa, who received appropriate therapy plus DP-b99 or appropriate therapy alone. The patients, all of whom had an NIH Stroke Scale (NIHSS) score of between 7 and 20 at baseline, were assessed at day 0 and day 90.
Although the trial did not attain its primary endpoint of significant change in NIHSS score across the entire treatment population, a significant change was apparent in those with moderate-to-severe stroke - or a score of 10 to 16 - at baseline.
Moreover, the rate of complete recovery in the drug treatment arm was twice that in the control arm, as measured by both the NIHSS, which is an objective measure of neurological function, and the Modified Rankin scale, an interview-based method for determining functional outcome after stroke.
"All three parameters - NIHSS alone, Rankin alone and the two combined - are extremely consistent," D-Pharm CEO Alex Kozak told BioWorld International. Using the combined scores, 38 percent of the treatment group attained complete recovery, compared to 19 percent for the control arm.
In addition, there was no difference in outcomes for those receiving DP-b99 within six hours of stroke and those receiving the drug between six and nine hours after stroke, which suggests that it could widen the treatment window.
Rehovot, Israel-based D-Pharm describes DP-b99, a lipophilic derivative of the known calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), as a "membrane active chelator." The compound can bind the metal ions zinc, calcium and copper but only in the lipid environment of cell membranes. It is thought to act by mopping up the excess metal ions that are released from intracellular stores following energy depletion caused by stroke damage.
"Multiple metal-dependent enzymes become overactive [after stroke]," Kozak said. Those contribute to the cascade of damaging events associated with such an event.
The compound has a different mode of action from thrombolytics, such as tissue plasminogen activator (tPA). "Our goal is to restore and protect brain tissue," Kozak said. The company is likely to include patients receiving tPA therapy in the upcoming trial, although its design has not yet been finalized. It also is planning to restrict the trial to those who have experienced moderate-to-severe stroke only.
D-Pharm granted an exclusive license for DP-b99 in South Korea to Seoul-based Yungjin Pharmaceutical Company Ltd. in October, but the compound remains unpartnered in other territories. The company, said Kozak, has not decided whether it will seek cash from investors to undertake the planned Phase III study itself, or enter into an alliance. "We are looking at what's on the table," he said.