Here's full text of BioWorld article, just in. Same freelance writer as Lancet story so parts are similar but what is most significant is the very strong endorsement given by a world authority not connected to Pharmos.
BioWorld International Nov. 4, 1998 Vol 3 (44), p. 1
Phase II Results Show Pressure Relief
Pharmos' Marijuana Analog Can Benefit Brain Injuries
by Rachelle H.B. Fishman
BioWorld International Correspondent
Rehovot, Israel -- The leading cause of death among youth in the Western world is not drug abuse, but the preventable neurological sequels of head trauma (mostly from traffic accidents), for which there is no approved treatment yet. Perhaps among the greatest of ironies, is that a marijuana analog, a non-psychotropic derivative, dexanabinoid, of Pharmos Corp., is now the first drug to definitively prevent brain damage, including death after head injury.
"Dexanabinol is the most promising neuroprotective agent seen to date," said Lawrence Marshall, a world authority on outcome after head trauma. Marshall is chief of neurological surgery from the University of California at San Diego.
"Phase II clinical trial results present outstanding and objective evidence via a pattern of intracranial pressure reduction with significantly improved outcome in severe head injury," said Marshall.
Two years ago, Pharmos mounted the phase II clinical trials in six trauma centers in Israel. These double-blind, randomized, placebo controlled studies examined 67 unconscious patients, mostly young men injured in traffic accidents. About half received dexanabinol and the remainder were given placebo as per protocal, within 6 hours of injury.
"Significant reduction in intracranial pressure below the 'damage
threshold' -- a key predictor of neurological outcome-- without
jeopardizing blood pressure was quite impressive in the dexanabinol treated group," said Marshall.
Numerous drugs and treatments have failed in Phase III clinical trials before. A handful of others now being tested in these big studies are yet to demonstrate decisive human benefit; these may still be stopped mid-trial like some of their predecessors if there is any hint of harm. Although each of these drugs is a star performer in laboratory studies, and each has a robust single mechanism of brain action, they have all failed in human studies.
Demand 'Difficult to OverState'
Dexanabinol is different from all other drugs in that it has a triple
mechanism of action, explained neuropharmacologist Anat Biegon, who is vice president of Pharmos Reseach & Development in Rehovot. "It is not only a calcium uptake inhibitor and an anti-inflammatory, but it is also an antioxidant, all of which are needed to prevent the cascade of brain injury from spreading and irreversibly damaging surrounding brain tissue, the cause of death or untreatable central disability."
Nachshon Knoller, a neurosurgeon from the Sheba Medical Center in Tel
Hashomer, Israel, is the Phase II study's principal investigator.
"Typically, an unconscious accident victim with head trauma when admitted to an emergency room today is likely to be given a cocktail of 20-30 different medications," he said. "Each deals with different indications of head trauma, but none deals with the brain and nerve damage resulting from the injury. The demand for a product like dexanabinol is difficult to overstate." This week, Knoller summarized the final Phase II study results before the National Neurotrauma Society in Los Angeles.
In the U.S. alone, about 370,000 patients with severe head trauma are
hospitalized every year, with the global incidence more than double that figure.
Pharmos managing director Michael Schickler "conservatively" estimates the potential market for dexanabinol in the treatment of severe head trauma at $500 million annually, but it could exceed $1 billion if other neurological conditions such as stroke and multiple sclerosis are treated with the drug.
Pharmos has demonstrated numerous other treatment possibilities in
laboratory studies, for example, dexanabinol diminishes neural damage
resulting from exposure to nerve gas in animals. "The market could be
substantially bigger if the drug's special triple ability is commandeered to treat other illnesses," said Schickler.
"With the positive results of the Phase II clinical trials in hand, we are organizing to start Phase III clinical trials in 1999 in the U.S., Israel, and Europe," said former Weizmann Institute molecular biologist Haim Aviv, who founded Pharmos and is its Chairman and CEO. Pharmos anticipates submitting the drug to the U.S. Food and Drug Administration for approval in three to four years.
This rosy outlook contrasts markedly with the company's frustration just a few months ago, when the National Institutes of Health commanded massive media coverage, commandeering front-page news for its OWN so-called "scientific breakthrough" with a different marijuana-derivative that they found to be a powerful antioxidant in an in vitro model of animal cells with the potential for treatment against head trauma and stroke.
"There is little question that the Hebrew University dexanabinol and
Pharmos research and development is years ahead for the same indication," said Schickler. The company, led by Aviv, has developed a long term strategy and, "We are looking at fulfilling or beating all set milestones well into the future," he said.
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