Phasers to Stun

Those of you who don't follow pharma as a fact of life may find the RFK, Jr. meme puzzling but not dangerous. Well, it is dangerous. But there is inherent danger in all of pharma, and in CNS space (central nervous system drugs) particularly. Such drugs rely, (almost?) exclusively on subjective surveys of symptoms and behaviors. The space is reknowned for 'unexpected' placebo effects in trials. After all, if what you're measuring isn't some sort of titer, can you trust all the humans involved in generating the data?

As we've found drugs for 'normal' disease, the CNS space emerges as a Final Frontier. What to do, what to do? Well... take a flyer. Most CNS maladies don't have the TAM of normal diseases, so end up with eardrum haemorrhaging prices. In all, billion dollar M&A is becoming more common. AbbVie dropped a cool $9 billion for an outfit that had a spiffy schizophrenia drug in trials. Turns out, the wheel came up 13 Red. Oops.

What is amazing is that the drug failed in PII!! That's not supposed to happen with a drug. The whole point of staged phase trials is that PII is supposed to, designed to, prove what was seen in pre-clinical and PI: the spiffy new drug is the silver bullet. The way that happens (most drug failures happen later in PIII) is that the sponsor, working with the CRO carefully vet sites, patients, data recorders, and the rest of the whole nine yards in order to have a sample (typically an order of magnitude smaller than the follow-on PIII) of patients who can't possibly fail. Or, that's the intent. Not this time.

In the first trial, AbbVie tracked numerically bigger reductions in PANSS scores, 14.7 and 16.5 points, in the emraclidine arms than in the placebo group, 13.5 points. However, the difference fell short of statistical significance. In the second trial, placebo beat one of the two emraclidine doses numerically, racking up a 16.1-point improvement compared to the 14.2-point reduction in the treatment group.
-- my emphasis

No doubt, finding drugs for such CNS maladies is a good thing. But we're not messing with some virus or bacterium that we can slay without hurting the rest of the body too, too much. The current crop of drugs targeting Alzheimer's, Parkinsons, ALS, and such are all in the same swamp.