zenmammon, I wasn't stating a consequence of the FDA requiring neurological examinations. Rather, if it were required, then the risk (discount) factor attributed to existing valuations would increase because of an additional level of proof of safety.
At this stage NEU hasn't published the results of a long term (12 months) toxicity study in rats or other animal model. The dosage rates and amounts in the clinical trials, especially the current pediatric Phase 2, are large. Some subjects are to receive 200mg per kg of body weight twice daily over the 42 day period if I've understood NEU's trial parameters correctly. If that assumption's correct (no cap based on bodyweight), then a 40kg patient, for instance, on 200mg/kg twice daily will ingest 0.672 kg over the trial (16g/day). If 200mg twice daily per kilo of bodyweight becomes the prescribed treatment regime on FDA approval then a 40kg patient will consume 5.84kg of trofinetide per annum. That's 14.6% of total body weight p.a. By comparison, the FDA recommended daily intake of sodium (salt) for instance is 2.4g.
This dose is a lot of drug to consume over an extended period, especially without any long term toxicity animal studies, despite the short term (28 day clinical studies) registering no SAEs and the drug being well tolerated at 70mg/kg twice daily (about a third of the maximum dosage for this pediatric study).
Given it's dosed orally, I don't know the uptake rate through the gut but, regardless of uptake, assume like most drugs 95% is eliminated on first pass via liver once in the bloodstream. The liver's doing a lot of lifting. Well published and discussed it the importance of gut health to physical and mental wellbeing. I have no idea what impact consumption at these levels in the trial will do long term on the gut, brain or liver. Trofinetide would be an exceptional drug if it were not to have a long term detrimental effect at any dose rates let alone 200mg/kg twice daily. For me, there's a high risk degree in the drug's approval path and I believe much higher than the market recognises judged on the current valuation. But, as many pundits have enlightened me on this forum, I don't know what I'm talking about. I guess they've already assessed all this and came to a different conclusion. If I were big pharma, I'd want to see at least the 12 month tox results in animals, which I believe are due in first half 2017, before making a move.
Expand
(20min delay)