Well as we’re all speculating about the Reach2HD results to pass the time – a few musings.
What strikes me is how similar the situation is to virtually exactly 6 years ago when PBT released its results from the P2a study of PBT2 in AD patients (PBT2-201). And how different many things are.
The design of the two trials are virtually identical. Both are P2a, testing different doses of PBT2 in modest sample of patients. With safety as the primary outcome and a suite of efficacy measures as the secondary outcomes.
The PBT2-201 AD study was completed in January 2008 and the results popped out under two months later. For Reach2HD the delay for the results is in the order of 6 months.
The trading halt for the AD study was announced in unambiguous terms … to release the outcome of the study. For Reach2HD the halt is requested to make an announcement about the results. As others have noted not necessarily to release the results.
The share price prior to release of the PBT2-201 results was relatively flat. The Chaiken Money Flow (CMF) indicator suggested shares were being neither accumulated or distributed.
In contrast to ReachHD where the share price increased significantly. But the CMF indicator showed negative divergence to the share price rise suggesting distribution. The marked sell off in the immediate past few days does not suggest positive results for anyone who believes in the efficient market hypothesis.
The results for PBT2-201 were announced by the company as positive. Safety was fine, a biomarker moved the right way, a dose response was seen and two tests for Execute Function were statistically significant at the 250mg level. There were no withdrawals due to safety.
How did the market react to the positive results? The share price opened at .495 - a couple of cents higher than the previous close and closed .695 (50% odd up) on heavy volume. But within a few days it was right back where it started.
For those buying in on the top it was about five and half years later before they got their money back. So what went wrong. Investor misunderstanding of the results plain and simple. P2a never proves anything. The results are exploratory not confirmatory. True believers continue to believe and skeptics remain skeptical.
The lesson from 2008 - if you see the share price rise 50% on the back of P2a sell first and think about it all later. And don’t buy into hype.
Fast forward to today. It seems to me the risk is to the downside. Anytime there are delays without good explanations from companies it usually spells trouble. The wording of the announcement doesn’t allay these concerns.
The market hopes for positive efficacy data from ReachHD for its own sake but perhaps more importantly as a replication of the earlier AD results. The earlier AD are not strong because they involved multiple testing. Good efficacy results from HD suggest the results from AD were not simply due to data mining and gives confidence in the P2b going forward.
In theory good efficacy results from ReachHD should not have been difficult. The bar is set pretty low in P2a with a predisposition to favour type 2 errors over type 1 errors. But the market bar is somewhat higher and the company seems to have made a meal of it. And this is being exploited in the current trading.
One confusing thing I hadn’t spotted with Reach2HD was that PBT had developed a new benchmarking system to assess the problems experienced by people with HD. According to PBT this new system addresses the challenges associated with assessing clinically relevant outcomes in HD where progressive motor, cognitive and psychiatric symptoms can interfere with comprehension of lengthy patient questionnaires. Baseline data for HD-PROP were collected from Reach2HD subjects. This new measure was also proposed by the CEO as an option for assessing the final clinical results the REACH2HD trial.
So therein are a couple of little warning bells about efficacy coming out of Reach2HD. The existing measures have problems. And in response the Reach2HD team developed a new measure. It is untried and untested.
And you have a mish mash of ideas in the announcement for HD-PROP. The researchers think it could be a good tool for helping identify areas that can be targeted for intervention. And they planned to re-administer the test in six (??) months to test for consistency in response. The CEO on the other hand thought it could be a good measure of change – and so you don’t want consistency of response.
In any event its hardly ideal because it doesn’t yield a simple calculable score. At T1 a patient identifies X as the key problem and this bothers him on a scale of 1-4 as a 4. Six months later he identifies Y as the key problem and he rates this as a 2. What to make of this in the context of an intervention trial is less than clear.
On this FDA meeting stuff. A end of P2a meeting with the FDA is where you work out a plan for how you might best test for efficacy in P2b. And hopefully your P1a results give some information that would be useful in making that decision. If the CEO in September knew the results were positive he would have released them.
So lots of ingredients for an interesting announcement when ever it comes. And that’s before you add ADRs, dowrampers on US sites, shorters etc etc into mix.
GLTH Southoz.
PBT Price at posting:
91.5¢ Sentiment: None Disclosure: Not Held
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