FDA most likely will ask to use regular melatonin as their placebo pill so they can see a head to head
study between the two. Tas vs melatonin. Most likely they probably already have and the result is " no difference". How do I know? Because Ramelteon (Rozerem) compared to melatonin shows no significant difference in showing that it is more effective in treating insomnia. There are no published studies out there that indicates whether ramelteon, in humans, is more or less safe or effective than the hormone melatonin which it mimics; melatonin is much less expensive and is widely available over-the-counter in the US and Canada. Both Ramelteon and Tasimelteon have high affinity to MT1 and MT2 receptors. Only Ramelteon have a high selectivity over the MT3 receptors. So I can safely say that Ramelteon is probably a better mimicker of the original, naturally occuring melatonin than Tasimelteon. By the way, Takeda discontinued their development of Ramelteon (Rozerem) in Europe on October 7, 2011 for treatment of insomnia. If FDA approves Tas, there's no doubt in my mind that Takeda will immediately go after the market of non-24 sleep cycle disorder.
That's actually wrong. Ramelteon is more selective for MT3 than MT2. But Tas actually has a much higher affinity as measured by the association constant (k) to both MT2 & MT3 than Ramelteon. I would post the link showing this, however Yahoo! will deleted my post. But you can Wikipedia Melatonin Receptor Agonists then go under subheading "current status" and you can see the association constants of both Tas & Ramelteon. Take a good look. Tas is exponentially higher. Thus it can be safely concluded that Tas will have a superior effect on both receptors.
Addressing your other point regarding Melatonin; why would companies spend millions developing melatonin agonists if melatonin itself achives the desired endpoints? Makes zero sense. The truth is receptors and the structure of melatonin have been known for decades. Researchers started to investigate modulations of the core structure to develop better agonists than melatonin; more potent, with better pharmacokinetics and longer half-life. Better pharmacokinetics as evidenced by Tas which clear has a higher association and is selective for the desired MT2 & MT3 receptors unlike it's predecessor melatonin. Based on what I'm seeing, Tas is poised to be best in show amongst all drugs acting on the melatonin receptors.
Mr. Bull...Again FDA might approve this drug, but what Mr Feuerstein probably called red flags and inconsistencies are the datas that can be manipulated depending on what biostatistical test you are using to show the efficacy of Tas. In 2008, VNDA again article written by Susan Jeffrey studied Tas with insomniacs, for some reason they abandoned that. Most likely in the hopes of using Tas on this unusual diagnosis called non-24 sleep cycle disorder. I know there are millions of dollars involve here, including time spent by researchers in labs and computers finding out how Tas can be more effective than Ram or even melatonin. But once money is involved, people's judgement gets really clouded. Greed takes over, even at the cost of causing loss of lives. Just be careful, the more I look at this, the more I see greed and manipulation and concocting datas. It looks like you're already winning big my friend. Good luck to whatever decision you would make.