zeev in one of my prior lives, I used to do clinical development of noven like patches. In fact noven sells a patch I worked on. Noven and many other makers of estrogen patches have always claimed that liver first pass effects would be decreased. but given the fact that there are at least two estrogen receptors and at least two progesterone receptors, which all have different tissue specific effector proteins, it is highly unlikely that this lack of first pass metabolism translating into a clinical effect will ever be verified. To make it worse, conjugated horse urine estrogens have variable receptor specific effects. Noven's patch might actually be better simply because it uses estrogen e-2. The rat has a monstrous liver estrogen effect. The human lacks the same response.
In fact it is unclear what the mortality was due too in the study, since previous studies have shown in hindsight, a protective effect. The doses of e plus p used in the study were high and fixed. clinical titration is important and often not done by docs, nor in the study. The serum level after dosing with an oral or a patch estrogen is so highly variable it is hard to even get an ANDA based on drug absorbtion kinetics, and in France you could not even get marketing approval with the use of serum studies- this was some time ago. My feeling is that everything was overdone by the press.
Merck and others including Lily and some European companies have good programs in tissue specific estrogens, as does the little company mentioned in science and in the times last week..
how this affects the stock price is not something for me to understand. but if people react like stocks, first there will be no one using it and then a gradual increase in users.
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