Washington Editor

Shares of Prana Biotechnology Ltd. skyrocketed Tuesday after Phase IIa study results showed that the firm's experimental Alzheimer's disease compound PBT2 was safe and tolerable, improved cognition and reduced the protein associated with neuronal injury.

Shares of the Melbourne, Australia-based-firm (NASDAQ:PRAN) rose more than 60 percent Tuesday before closing at $5.59, an increase of $1.49 or 36.34 percent.

PBT2, a metal-protein attenuating compound, inhibits amyloid beta protein 42, or Abeta 42, the toxic peptide associated with the functional damage of Alzheimer's disease.

The randomized, double-blind, placebo-controlled Phase IIa study, conducted at 15 clinical sites in Sweden and Australia, assessed the safety and tolerability of PBT2 and the compound's effectiveness in slowing progression of disease in 78 patients with early, mild to moderate Alzheimer's disease.

Treatment groups received either once-daily oral capsules of PBT2 50 mg or 250 mg or placebo over 12 weeks.

More patients received the higher dosage of the drug, coordinating investigator Craig Ritchie, a psychiatrist and clinical research fellow at the Imperial College London, told BioWorld Today by phone from London, with 29 getting PBT2 250-mg, 20 receiving 50 mg of the drug and 29 taking placebo.

The 250-mg dosage showed a highly statistically significant reduction of 60 percent in Abeta 42 in cerebrospinal fluid vs. placebo, said Prana co-founder Rudy Tanzi, professor of neurology at Harvard Medical School and director of the genetics and aging unit at Massachusetts General Hospital in Boston.

In addition, he told BioWorld Today, there was improvement in cognitive tests for executive memory - the type of memory used in day-to-day functioning.

"The degree to which these results were positive in terms of Abeta and the cognitive findings were surprising for all of us," said Tanzi, a member of Prana's scientific board. "We were hoping for good results, but these results really went beyond our expectations for only a 12-week trial," he added.

The Phase IIa study met its primary endpoint of safety and tolerability, demonstrating that there was no difference between both dosages of the compound and placebo, Ritchie said. He added that there were no serious adverse events related to the drug and no study withdrawals because of adverse events.

"We kept triple checking and couldn't find any," he said.

Tanzi, who founded Prana in 1994 as a virtual company from his Massachusetts lab, noted that the Phase IIa findings sprang from 15 years of research based on his original findings that metals like zinc and copper drive the aggregation of the Abeta peptide, which is a key component of senile amyloid plaques in Alzheimer's disease.

Firms involved in R&D for Alzheimer's disease targeting Abeta as a way of treating the condition are either trying to curb the production of Abeta or attempting to clear it from of the brain, Tanzi explained.

Prana's approach is using small molecules to clear Abeta by preventing its aggregation in the brain, he noted.

"If you don't let Abeta interact with zinc and copper, then Abeta will not aggregate, and it's very easy for the brain to clear it out into the bloodstream," Tanzi said. "If you want to clear Abeta from the brain, you need to stop it from aggregating."

Tanzi emphasized that Prana's PBT2 is not a chelation therapy, a controversial treatment that uses a molecule or chemical to remove a heavy metal, such as lead or mercury, from the body. "There's been a real misperception about this program in the past among academics, among pharma and biotechs, where they think this is chelation therapy, but it is not," he insisted. "The drug we are using is not a chelator, it just has the property of being able to get into the brain and bind to Abeta."

PBT2, Tanzi said, takes the metals away from Abeta and makes them available to be used by other proteins or enzymes in the brain without depleting the body of those metals.

"So if anything, it actually makes metals more available to the enzymes that need them," he said.

Prana now plans to further progress PBT2 into larger and longer clinical trials to investigate its potential as a disease-modifying drug.

Ritchie said the next study will involve "several hundred" patients, but was unable to provide any other details.

A spokeswoman for the firm said Prana currently is in discussions about partnering PBT2 with other companies.

As for Tanzi, after spending 15 years researching the effects of metal-protein attenuating compounds in Alzheimer's disease, "I'm going to enjoy the moment" of celebrating the positive results of the Phase IIa study.

"I'm just really happy about that," he said. "I'm just hoping that we can make a difference in this disease. It's just cool to sit back and think over the last 15 years of how far it's gone."