A number of readers have emailed me to ask my thoughts on the Neuren Phase II outcome in Fragile X. I initially wasn’t inclined to pass comment, mainly because I didn’t feel like getting a lot of flack from angry parents of Fragile X patients, criticising me for my lack of faith in Neuren (ASX : NEU). But then if I am going to be a reasonable human being – and in consideration of my generally lukewarm sentiment toward this company – I should be fair and acknowledge interesting results when they arise.
And the stated results from Neuren’s Phase II study in Fragile X (NCT01894958) are interesting.
As usual, it was an appropriately sensationalist ASX disclosure, including a nice trading halt for additional impact, but the data is interesting (I repeat). Based on what Neuren has presented, there does appear to be a dose-dependent relationship for the secondary outcome (behaviour-related measures), though it does need to be recognised that these are fairly tough endpoints to quantitate and this is a very small study. Still, considering the high quality of the clinical sites and the basic structure of the trial design, it looks like Neuren got something more than just a basic safety signal, which is great.
Shareholders should be happy.
Having said this, there really was never going to be much of a concern about safety for this drug because it has already been studied in a fairly large number of patients, and in a sense that’s the slightly annoying thing about this trial. It’s like somehow we were supposed to have forgotten about the history of this drug. As such, the study is constructed as though there really are safety/AE concerns at this dose range, when there probably aren’t. Therefore the headline that the study met its primary end-point is a bit of a yawn if I am being candid with you. On the other hand, if I am being kind to Richard and the team, I suppose the rationale for such a small study (25 or less patients per arm) is that perhaps these patients aren’t so easy to come by in a clinical trial setting.
Hopefully that’s the reason for such a small study that basically isn’t powered to study anything other than safety.
The data, as presented, looks nice but it is still worth noting that the error bars have fairly significant overlap between dose cohorts (and placebo) and the rating scales, as presented, are a little bit arbitrary. The data summary shows trends, but there is also a lot of quasi-science in the presentation of the information that, as usual, gives me the shits. The key piece of information, which is “the effects observed following treatment with the low dose of trofinetide (35 mg/kg twice daily) were less consistent and the magnitude of improvement did not meet pre-specified targets, but there was evidence of a dose response” is mostly buried in a lot of enthusiastic rah rah.
And… the company has presented a visual and “quantitative” compilation of what are supposed to be several distinct data points. If you look at the clinicaltrials.gov entry for this study, one can clearly ascertain that the various secondary outcome measures as presented by the company are basically combination scores. As such there really isn’t enough data presented to tell you whether or not this data is more than just a little bit exciting. It would have been nice to see the individual measures as a function of dose/placebo, rather than “scorecards” (i.e. rolled-up numbers). By my count there should be at least 8 graphs for behaviour-related secondary endpoints and 12 or more graphs for outcome measures (depending on how you compare “during” and “post”-therapy for such an incredibly short study).
So my take on the data? It looks interesting, but it also looks incomplete. It probably does pave the way for further clinical development, though whether this amounts to more than just another Phase II study at a higher dose will be mostly up to the FDA. They’ll care about the minutiae of the data, but they will also be keen to see drug candidates progress in a very difficult patient population like this. Since the FDA’s biggest concern is safety, the company certainly has more than a “shot” at moving ahead.
Oh, and of course, the company will no doubt publish the data in a top-tier neuroscience journal where all the data is laid bare for the world to see. Just like they did with all their other clinical studies that reported positive and exciting outcomes.