That is totally bogus and an oversimplification to say the least. To assume each arm exhibited the same level of placebo affect is naïve... and certainly shows how biotech isn't for everyone.
All aspects of the trial introduces elements that can adversely affect the placebo result, especially in the case where hopeful parents are answering test questions on behalf of the patient. The fact that no other Rett trial has ever produced such an extraordinarily large placebo effect suggests there are unusual conditions to it. One was mentioned by Walter E Kaufmann, MD, Chief Scientific Officer of Anavex commented, “We believe that a high placebo response may have masked the therapeutic effect of this innovative orally available molecule. High placebo responses are well documented especially in pediatric clinical studies. Although data analysis is ongoing, the early conclusion is that the placebo rate could have been higher in the study due to a slight imbalance in disease severity at baseline, across the treatment arms, and the 2 to 1 drug to placebo randomization ratio." The other is the lack of SAEs, which results in a truly blinded trial. Unlike trofinetide, where due to the side effects and lack thereof in the placebo group, parents virtually "knew" whether their daughters were on the drug or not. Thus, the trofinetide trail had more realistic placebo results than that of blarcamesine... where hopeful parents were "seeing" improvements that weren't really there. Those perceived improvements were likely the result of positive feedback from the patient to the positive influence of the parents. Had there been gastro issues with blarcamesine, it would be a good bet that the "placebo effect" would've been much lower, in the absence of an SAE (i.e. less hopeful parents). In fact, it wouldn't have taken much of a reduced placebo result for the RSBQ to be stat. sig. at the arbitrary p-value of .05 (compared to the calculated .063). Another factor, that negatively impacted the results, was that most of the interviews were done remotely, rather in person (due to Covid).
For the trofinetide trial, where parents virtually knew that their daughters were on the drug (due to gastro issues), they still couldn't bias their evaluation to a higher "hopeful" average result beyond -5.1 (which is less than the blarcamesine placebo result) because the true benefit was only marginal.
We'll see what the regulators have to say in review of the total trial data, OLE, RWE and perhaps the influence of the Rett Syndrome org. Deciding to run another trial, as a conservative measure, doesn't mean that all regulators have reviewed the data.
