Huntington's Drug Shows Promise in Midstage Study

Megan Brooks

February 19, 2014

PBT2, an experimental metal-protein–attenuating compound, met the primary outcome of safety and tolerability in a midstage study of patients with Huntington's disease, Prana Biotechnology, the Australia-based company developing the drug, reported this week.

In the Reach2HD phase 2 conducted in the United States and Australia, 109 patients with Huntington's disease were randomly allocated to receive PBT2 (100 or 250 mg daily) or placebo for 26 weeks; 104 participants (95%) completed the study on their assigned dose.

The drug met the primary study endpoints of safety and tolerability, the company said. Adverse events did not substantially differ across the 2 PBT2 dose groups and the placebo group. Of the 10 reported serious adverse events, only 1 was deemed by the clinical site investigator to be related to drug treatment.  

For the secondary study endpoint of efficacy, the effects of PBT2 were tested on cognition, motor performance, behavior, and functional capacity, of which cognition was prespecified as the main efficacy outcome.

Performance on the Trail Making Test Part B significantly improved in the higher-dose PBT2 group compared with the placebo group at both 12 (P < .001) and 26 (P = .042) weeks, the company said. This test measures executive function, which is often impaired early in the course of Huntington's disease and is also affected in Alzheimer's disease.

"This is the first time we have observed dose-related slowing in functional decline over a 6-month period of treatment," Ira Shoulson, MD, professor of neurology at Georgetown University, Washington, DC, and chair of the Huntington Study Group, who was not involved in the trial but serves as an advisor to Prana Biotechnology, said in a statement.

Preliminary evidence from a pilot imaging substudy suggests that PBT2, 250 mg, reduced atrophy of brain tissue in areas affected in Huntington's disease, the company said.

"Despite the very small number of patients in the substudy, the data are suggestive of a beneficial effect of PBT2 in regions of the brain that are known to be vulnerable to Huntington disease," said Diana Rosas, MD, associate professor of neurology at Harvard Medical School, Boston, Massachusetts, and the study's coprincipal Investigator who conducted the imaging substudy.

On the basis of these findings, Prana said it would start a pivotal phase 3 study of PBT2 to treat Huntington's disease. The company is also testing the drug for Alzheimer's disease, with promising results, as reported previously by Medscape Medical News.

In a statement, Rudy Tanzi, PhD, professor of neurology at Harvard Medical School and Prana's chief scientific advisor, said finding "significant improvement in executive function with PBT2 in this study of Huntington disease and the previously reported Alzheimer's trial, suggests a common mechanism for neurodegeneration in these diseases based on metal interactions. In my opinion, these findings significantly elevate the potential for PBT2 as an effective therapy for both Huntington disease and Alzheimer's disease."


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