AI
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Wednesday, July 21, 2004 10:34:08 AM
Nitromed:
There is some silliness being written in the media regarding the nitric oxide effect, so let's clear that up first.
Nitric oxide is released from the endothelial cells that line arteries. It diffuses to the smooth muscle lining the arteries and activates the soluble pool of guanylate cyclase, an enzyme that generates the intracellular messenger cGMP (cyclic GMP) through the catabolism of GTP. cGMP activates another protein, cGMP-dependent protein kinase (also called Protein kinase G) to increase the activity of myosin phosphatase, an intracellular enzyme that acts to antagonize the contractility of smooth muscle. Therefore, administration of nitric oxide through a nitric oxide donor starts the cascade to relax the smooth muscle lining arteries, decreasing peripheral resistance and lowering blood flow.
The concept that blacks have insufficient nitric oxide is a nonsense comment that i would expect from any analyst working at a securities firm
The second point I'd like to make is how terribly difficult it is to design a clear, unequivocal study in the cardiovascular setting. Patient stratification and the balance between groups with respect to New York Heart Association (NYHA) class settings and additional drug usage (beta blockers) makes it very tricky. I've been in countless cardiology meetings where the docs just blast trial design and are loathe to change their prescription preferences based on what they perceive to be trials with deficient designs.
Therefore, the only real recourse for companies is to have their product actually included in the treatment recommendations put out by the larger collaborative groups or not-for-profit organizations such as the American Heart Association. With Bidil, it does not introduce a novel treatment concept, but rather fortifies the concept that amelioration of hypertension is a clinically relevant endpoint in a population known to be at higher risk for hypertension. For me, this study is more a population study than the study of a new treatment modality. For this reason, I have serious reservations as to whether or not Bidil will actually sell in the marketplace. My bet is that it won't.
No position, short or long.
There is some silliness being written in the media regarding the nitric oxide effect, so let's clear that up first.
Nitric oxide is released from the endothelial cells that line arteries. It diffuses to the smooth muscle lining the arteries and activates the soluble pool of guanylate cyclase, an enzyme that generates the intracellular messenger cGMP (cyclic GMP) through the catabolism of GTP. cGMP activates another protein, cGMP-dependent protein kinase (also called Protein kinase G) to increase the activity of myosin phosphatase, an intracellular enzyme that acts to antagonize the contractility of smooth muscle. Therefore, administration of nitric oxide through a nitric oxide donor starts the cascade to relax the smooth muscle lining arteries, decreasing peripheral resistance and lowering blood flow.
The concept that blacks have insufficient nitric oxide is a nonsense comment that i would expect from any analyst working at a securities firm
The second point I'd like to make is how terribly difficult it is to design a clear, unequivocal study in the cardiovascular setting. Patient stratification and the balance between groups with respect to New York Heart Association (NYHA) class settings and additional drug usage (beta blockers) makes it very tricky. I've been in countless cardiology meetings where the docs just blast trial design and are loathe to change their prescription preferences based on what they perceive to be trials with deficient designs.
Therefore, the only real recourse for companies is to have their product actually included in the treatment recommendations put out by the larger collaborative groups or not-for-profit organizations such as the American Heart Association. With Bidil, it does not introduce a novel treatment concept, but rather fortifies the concept that amelioration of hypertension is a clinically relevant endpoint in a population known to be at higher risk for hypertension. For me, this study is more a population study than the study of a new treatment modality. For this reason, I have serious reservations as to whether or not Bidil will actually sell in the marketplace. My bet is that it won't.
No position, short or long.
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