I’ve been saying a lot of unkind things about Axovant, the insta-company that’s taking a discarded GSK Alzheimer’s candidate and running with it. But thanks to Adam Feuerstein, I have another company to roll my eyes about. They have a completely different Alzheimer’s plan – they’ve taken a discarded Pfizer candidate and are running with it. The drug in question is azeliragon, formerly PF-04494700, targeting RAGE (the receptor for advanced glycation endpoints), and the company’s press material about it includes a qualifying statement that you don’t run across very often:
“Despite the 20mg/day dose being stopped by the DMC due to acute, reversible, concentration dependent cognitive worsening and the study being prematurely stopped for apparent futility, the study achieved its prespecified objective demonstrating a statistically significant 3.1 point different (p = 0.008) favoring azeliragon 5mg/day over placebo at 18 months in patients with mild to moderate AD.”
That’s in the ADASCog rating, but the overview goes on to say that “the study was not powered to show significant differences for global, functional, cognitive and behavioral secondary endpoints”. Here are some publications on the trials themselves. Now, being generous, one could conclude that there’s a chance for this to work – after all the 5mg/day numbers are, presumably, what they are. But at a 4x higher dose, big trial-ending trouble was seen, of just the sort that you can’t have in Alzheimer’s (“acute cognitive worsening”). And we have no idea where that kicks in between the two doses. This is a very, very tight window between what could be a good effect and what is certainly a very bad one, which is surely why Pfizer dropped the compound like it was giving off gamma rays and has not returned to it.
All Alzheimer’s clinical candidates are longshots, by definition. But this one is a longshot longshot. I hope that people are only putting money into it that they can afford to lose, but I also hope that when I see elderly customers shuffling up to the lottery ticket register, and I think I’m wrong about that one, too.
So who are these people? The company is vTv Therapeutics (that’s how they spell it), and they’re heading for an IPO. The bio of their CEO, Stephen Holcombe, says that he brings “brings over 23 years of financial and managerial experience” to the table. Looking closer, though, that experience is with KPMG Peat Marwick, a cell phone company, and an e-commerce provider to the construction industry. Unless he’s been hitting the books at night, and perhaps he has, one cannot guess that he knows anything about drug development. Their CSO is Carmen Valcarce, ex-Novo Nordisk. But the chairman of the board, that’s the really interesting part: it’s one Jeff Kindler, whom many will recognize as Pfizer’s onetime CEO. And there are many ex-Pfizer employees who have opinions on how much he knows about drug development, for sure. His departure from the company was the subject of a truly bizarre article the next year, one that I think set off a lot of discontent among the non-executive-suite folks at the company.
So vTv is going to be interesting to watch. The Alzheimer’s program isn’t their only shot, as opposed to Axovant, I will give them that. But some of their other assets have been kicking around for a while, too, such as the ones from when the company was known as TransTech Pharma (like TTP339, a glucokinase activator). Azeliragon itself was originally a TransTech compound, licensed to Pfizer, but it boomeranged back to them after the Phase II results. The company has changed its name and rebranded itself as an Alzheimer’s therapy play, and so off to the NASDAQ they go.