Alzheimer’s Drug PBT2 Shows Promise in Early Testing

September 16, 2008

Setember 16, 2008

Men and women with early Alzheimer’s disease showed modest benefits from PBT2, an experimental drug now in mid-stage testing. The medication, made by the drug company Prana, proved safe in the small trial.

In the study, a Phase 2 trial of 75 patients with early-stage Alzheimer’s, patients received one of two doses of the drug (50 milligrams or 250 milligrams) or a placebo. Neither doctors nor patients knew who was getting the drug or a look-alike dummy pill.

After 12 weeks of therapy, no serious adverse effects were noted. Memory and thinking tests showed that those taking the drug had improvements in the “executive function” related to the frontal lobes of the brain.

A doctor who commented on the study in The Lancet Neurology, where the results were published online, noted that the drug “must still overcome the high hurdle of additional safety and efficacy testing in large-scale clinical trials.” Phase 2 trials are conducted to test the safety of a drug, as well as potential benefits. If results are positive, a much larger number of patients may be recruited for late-stage, Phase 3 testing.

The experimental compound, PBT2, affects levels of copper and zinc in the brain and is believed to help prevent the buildup of toxic beta-amyloid, a protein that builds up in the brains of those with Alzheimer’s disease.

The drug is part of a new generation of Alzheimer’s drugs now in testing that aim to modify the course of the disease. The hope is that such drugs may alter proteins like beta-amyloid and tau that buildup in the brain in Alzheimer’s and thereby halt, or even reverse, the ravages of the disease. Current Alzheimer’s medicines, like Aricept, Exelon or Razadyne, may ease symptoms for a time but do nothing to stop the relentless downward progression of disease.

In the current study, 42 of the 78 patients experienced side effects, but they were generally mild, and researchers were encouraged to continue testing. Those who were taking the drug scored better on executive function tests that measure things like decision making; individuals taking the higher dose scored higher on the tests overall. Blood tests also suggested the drug helped to diminish levels of toxic beta-amyloid in the brain.

Future testing will be required in more people for a longer period. Experts caution that many drugs that look promising in mid-stage, Phase 2 testing fail with further follow-up, so that it is far from certain whether PBT2 will ever be available as an Alzheimer’s treatment.

For example, earlier this year, many researchers were excited about Flurizan, a new-generation Alzheimer’s drug that is aimed at toxic beta-amyloid. It showed promise in improving thinking and memory in mid-stage trials but failed to show benefits in larger, late-stage testing. [See the story, “Alzheimer’s Drug Flurizan Fails in Late-Stage Testing“]

More recently, another drug called bapineuzumab showed some promise in mid-stage trials of 240 people with early to moderate Alzheimer’s. [See the story,”Experimental Alzheimer’s Drug Advances to Late-Stage Trials“] Although late-stage testing is proceeding, many remain cautious. The drug did not help carriers of the APO-E4 gene, which is more common in  those with Alzheimer’s than in those in the general population.  In addition, a dozen patients developed fluid buildup in the brain, a potentially serious side effect that required they stop taking the drug.

Another drug, an antihistamine from Russia called Dimebon has, like PBT2, also shown promise in mid-stage testing. Currently, the drug is beginning phase 3, late-stage trials, which involve greater numbers of men and women. Those trials are scheduled to last six months.

By www.ALZinfo.org, The Alzheimer’s Information Site. Reviewed by William J. Netzer, Ph.D., Fisher Center for Alzheimer’s Research Foundation at The Rockefeller University.


Lars Lnnfelt, M.D., Kaj Blennow, M.D., Henrik Zetterberg, M.D., et al: “Safety, Efficacy, and Biomarker Findings of PBT2 in Targeting Beta-Amyloid as a Modifying Therapy for Alzheimer’s Disease: A Phase IIa, Double-Blind, Randomised, Placebo-Controlled Trial.” The Lancet Neurology, July 29, 2008, DOI: 10:1016/S1474-4422(08)70167-4.


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