new tanzi comment on reach2hd trials, page-2

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Rudy Tanzi
Massachusetts General Hospital
Posted: 21 Feb 2014
While we will have to wait for the publication of the peer-reviewed paper to properly assess the results of the Reach2HD Huntington disease (HD) trial, for those interested, I have summarized below the key findings that were provided in Prana's press release on the results of the trial. What is most interesting to me is that this is the second time that treatment with PBT2 (250 mg) led to statistically significant improved performance on the Trail Making Test B for executive function, the first time being in Prana's 2008 phase 2A Alzheimer's disease trial. In my opinion, this suggests a possible common mechanism of action in these two trials and warrants further confirmatory trials.

Key Points:

1. Primary endpoints of safety and tolerability were met. Ninety-five percent (104 of 109) of participants completed the study on their assigned dose. There were no substantial differences in adverse events across the two PBT2 dose groups and the placebo group. One of the 10 reported serious adverse events was deemed by the clinical site investigator to be related to drug treatment. This occurred during the four-week follow-up period (i.e., not on study drug) after completing the six-month treatment.

2. Regarding the secondary endpoints on efficacy, the effects of PBT2 were tested on cognition, motor performance, behavior, and functional capacity, of which cognition was pre-specified as the main efficacy outcome. Across all study participants, there was statistically significant improvement in performance only on the Trail Making Test Part B in the PBT2 (250 mg) group compared to placebo at both 12 (p<0.001) and 26 weeks (p=0.042). Trail Making Test Part B is a measure of executive function (e.g., ability to plan activities), which is impaired early in the course of Huntington's disease and is also affected in Alzheimer’s disease.

3. Given the evidence from an earlier trial (2008), which showed that PBT2 improved executive function in Alzheimer’s disease patients, the Reach2HD trial included a plan to assess the effects of PBT2 on an Executive Function Composite z-score. There was a statistically significant improvement in this z-score (p=0.038), but only in a pre-specified analysis of Reach2HD participants with early stage Huntington disease, as measured by their Total Functioning Capacity score. Across all study participants, who comprised both early and mid-stage HD patients, there was a trend to improvement (p=0.069).

4. No significant improvements were seen on other secondary efficacy measures in the study.

5. An exploratory sub-study using magnetic resonance imaging (MRI) was performed in a small subset of patients (n=6) to map anatomical changes in brain structure. In the combined PBT2 groups (n=4) a preliminary observation of reduction in atrophy of brain tissue in regions of the brain known to be affected by Huntington's disease was observed compared to the placebo group.

Disclosure: I am the scientific co-founder of Prana Biotechnology. I am paid consultant of Prana Biotechnology (Chief Scientific Advisor) and a shareholder.