By Debbie Strickland
Neurex Corp. and the Warner-Lambert Co. have hit the restart button on a Phase III head trauma trial that the companies paused in late July in order to review data from an earlier study.
The companies told clinical investigators they may resume enrollment immediately in the Phase III test of SNX-111 for the prevention of neurological damage in patients with severe head trauma. The study design is unchanged.
Also under development in a separate program for pain relief, SNX-111 is a synthetic peptide based on a derivative from the venom of the Conus snail. The compound is a neuron-specific calcium channel blocker that inhibits neurotransmitter release.
The head trauma trial was halted July 28 after clinical data from a 70-patient Phase I/II study failed to demonstrate a clear risk/benefit ratio in the group receiving the drug.
"A disparity in the data in the SNX-111 and the placebo groups caused the initial concern," said Paul Goddard, chairman and CEO of Menlo Park, Calif.-based Neurex. "The detailed data analyses [conducted over the last month] indicated that this appeared to be due to small patient numbers and an unfortunate distribution of patients at randomization between the placebo and SNX-111-treated groups."
The decision to continue the study came after the data were reviewed by the trial's Data Safety Monitoring Committee, the American Brain Injury Consortium and the FDA.
Head injury trials, Goddard noted, are always difficult to design and run.
"Most of the patients have multiple injuries, which means that not only do they have head trauma but they generally have damage to other organs," said Goddard. These other injuries can exert a "significant . . . influence on the outcome in patients, both in terms of morbidity and mortality."
Neurex and Morris Plains, N.J.-based Warner-Lambert, which is conducting the head trauma trial, expect the 800-patient study to take at least two years. The companies also are developing the drug for other ischemia-associated conditions, including prevention of neurological damage in stroke patients, and for the treatment of such damage in patients who have undergone coronary artery bypass graft surgery.
Although the head trauma trial's re-initiation is good news for Neurex, the development of SNX-111 in this indication is a long-term project and must be viewed in perspective, Goddard said.
In June, an FDA advisory panel recommended approval of Neurex's lead product, Corlopam, a dopamine (DA-1) receptor agonist that allows precise blood pressure control through systemic vasodilation.
"We expect Corlopam approval this year and a filing for SNX-111 in pain by the middle of next year," Goddard told BioWorld Today. "Those are the two near-term value drivers, I believe, in the company. The head trauma [indication] has always been a longer-term opportunity."
Indeed, the potential payoff from the head trauma indication has not been factored into analysts' projections, said Scott Sacane, an analyst for Montgomery Securities, in New York.
"Analysts that cover the company, including myself, have yet to include any revenue contribution from head trauma in our long-term revenue projections," Sacane said. "If the reinstatement of the Phase III head trauma trials proves to be a successful program, it will be all upside to the revenue and earnings models that most analysts have put together."
Neurex ended the second quarter with $72 million in cash and a monthly burn rate of about $2 million. The company's shares (NASDAQ:NXCO) closed Wednesday at $13.875, up $0.688.
Neurex is independently developing SNX-111 as a treatment for pain. Two Phase III clinical trials, both in patients with long-term or chronic pain, are expected to reach the goal of enrolling a combined 300 patients by year end. In these studies, SNX-111 is administered intrathecally at doses 10,000 times lower than those being employed intravenously in the head trauma study.
In the pain program, Neurex is collaborating with Medtronic Inc., of Minneapolis. An implantable Medtronic pump delivers the drug to the spine in an effort to prevent nerve cells from sending pain signals to the brain. *