Primary Arterial Hypertension News - Menu Fat Chances
Matthew Herper NEW YORK - 05.11.05 - Despite the fact that obesity is one of the biggest preventable causes of death, investors may find that fat-fighting drugs are a far riskier business than they seem. Take today's announcement from Arena Pharmaceuticals (nasdaq: ARNA - news - people ), a biotech with a market capitalization of a mere $230 million. Arena's shares jumped 20% on news that its experimental pill, APD356, helped patients shed an average of 2.9 pounds in only 28 days. But the short duration of the study means it may not be able to answer some important safety questions. "It's promising and also a bit scary," says Steven Nissen, a cardiologist at the Cleveland Clinic who is working on another obesity drug, the much anticipated Acomplia from Sanofi-Aventis (nyse: SNY - news - people ). Arena's pill was born from one of the drug industry's biggest disasters: the diet combo fen-phen. That combo of two medicines, fenfluramine and phentermine, damaged the heart valves of some of the people who took it. Fenfluramine was withdrawn from the market, resulting in massive legal costs for drugmaker Wyeth (nyse: WYE - news - people ), which has set aside some $21 billion to pay for legal settlements related to the drug. Some analysts expect that number could grow even more. Fenfluramine worked by increasing the amount of serotonin in the brain in a way that reduced appetite. But Arena argues that fen-phen hit more brain receptors than was necessary. Its APD356 is far more specific, and so far the heart valve damage that led to fen-phen's withdrawal has not reared its head. Jack Lief, Arena's chief executive, points out that the heart valve side effects were rare, and that a big clinical trial could settle the issue. The current trial is too small to lead to definite conclusions. To finish developing the drug, Arena may need to enlist a big pharmaceutical partner. "I'm looking for an over-the-top kind of deal," says Lief. But the field of anti-obesity medicines is littered with disappointments. Fen-phen was effective but proved deadly, and many doctors say it was overused on patients whose obesity was cosmetic and not a health risk. Meridia, from Abbott Laboratories (nyse: ABT - news - people ), and Xenical, from Roche, have both failed to ignite, partly because of side effects. Sanofi's new entrant, Acomplia, which is expected to be submitted to the FDA this year, is the exception that proves the rule. The drug is, in a sense, the anti-marijuana. It blocks the same receptors that give pot smokers the munchies, and, in doing so, helps overweight patients lose weight. It also makes it easier for tobacco smokers to quit smoking. (See: "The Ultimate Pill") Some analysts predict annual sales of $5 billion or more for Acomplia. But the reason for the optimism is that the same cannabinoid (from cannabis or marijuana) receptors that reduce cravings are also present in fat cells. Along with helping heavy patients lose weight (it doesn't seem to work as well on thinner patients), Acomplia also raises good cholesterol, cuts bad cholesterol, reduces triglicerides and generally seems as if it should reduce the risk of heart disease and other obesity-related killers. The trial in which Nissen is involved aims at proving that the drug will reduce the amount of plaque that builds up in arteries. Acomplia's potential is to be a chronic medicine on a par with Pfizer's (nyse: PFE - news - people ) cholesterol-lowering medicine Lipitor, the world's top seller with annual sales of $11 billion. Bristol-Myers Squibb (nyse: BMY - news - people ) recently licensed its own Acomplia-like drug, which is in early safety trials.
An appetite-reducing drug that works in the brain probably doesn't have that kind of potential. Even if Arena's pill clears all safety hurdles, investors might want to be careful about expecting huge potential from it. But this little company does have some other irons in the fire, including a couple other experimental drugs, including a sleeping pill. Arena also recently signed a deal that could be worth $317 million with Johnson & Johnson (nyse: JNJ - news - people ) to develop diabetes medicines. Lief says it is the biggest such deal ever in biotech.
Viagra Cialis and Levitra Benefit Heart and other Organs - Erectile Dysfunction ED Drugs Improve Blood Flow According to Study
June 16th 2006 - Researchers say that Viagra and other erectile dysfunction drugs benefit other systems in the body. This is according to Ernst R. Schwarz, M.D., Ph.D., a cardiologist at Cedars-Sinai Medical Center who specializes in therapies for men who suffer from erectile dysfunction (ED). Many of his patients have heart problems, diabetes, high blood pressure or other related conditions.
John Hopkins researchers found in a previous study that Viagra reduced the stimulatory effects of hormonal stress on the heart by half. Schwarz says the drug, and other erectile dysfunction drugs like Levitra® (vardenafil) and Cialis® (tadalafil), benefits various organs with few side effects.
Schwarz said, “When we look at all the different organ systems – the blood, the heart, the lungs, blood flow in the brain – there are hardly any negative side effects. In fact, just the opposite is true. There are beneficial effects for primary pulmonary hypertension, as well as for conditions such as heart failure and lack of oxygen in the heart.”
There are no real long term studies available on the products. According to Schwarz, “The only issue is that the data we have are from relatively short-term studies. Viagra has been on the market since 1998 and the other two PDE-5 inhibitors were approved by the FDA in 2003. Therefore, we do not have multi-year follow-up studies. On the other hand, the drugs have been on the market for several years now and there have been no reports of negative long-term effects.”
Recently the Food and Drug Administration (FDA) approved a reformulation of sildenafil (Viagra) for the treatment of primary pulmonary hypertension, a disease that tends to occur in young women, causing elevated blood pressures in the lung that can lead to heart failure and early death.
There are differences in the three medications, but they all limit the activity of the enzyme phosphodiesterase-5 (PDE-5), which is found in tissues and vessels of the penis, blood platelets, and smooth muscle of blood vessels. The erectile dysfunction condition is solved when they constrain the enzyme’s action which results in increased levels of cyclic guanosine monophosphate (cGMP) and nitric oxide (NO), biochemicals that promote smooth muscle relaxation and increased blood flow in erectile tissue.
The researchers say that PDE-5 inhibitors can be used to treat erectile “dysfunction even for many men who also have diabetes, those who are older, and those who have co-existing ischemic heart disease.” Since PDE-5 can smooth muscles of the systemic arteries and veins throughout the body, the use has been associated with various cardiovascular effects.
Schwarz says “The original intention was to develop PDE-5 inhibitors as a treatment for angina, chest pain that occurs when the heart is starved for oxygen.” He added, “As such, their effects on the heart appear to be all beneficial. Nitrates and other substances commonly used to improve blood flow and oxygenation to the heart muscle have a side effect that we call the ‘steal phenomenon,’ in which blood is taken away from underperfused (flow-restricted) areas to improve blood flow in normal areas. In contrast, PDE-5 inhibitors actually improve blood flow even in areas where there is a blockage of an artery, thereby having a protective effect on the heart muscle.”
There was some concern with sight-loss (NAION or non-arteric anterior ischemic optic neuropathy) in patients taking the drugs. But according to the researchers, after an analysis of 13,000 men and more than 35,000 patient observations, they found the “occurrence of the visual disorder to be similar to that of the general population.”
Among other findings:
• Although the enzyme PDE-5 has been found in tissue and arteries of the brain, sildenafil does not appear to dilate cerebral arteries or have an effect on cerebral blood flow or blood flow velocity, an indication that there is no increased risk of stroke or hemorrhage.
• PDE-5 exists in blood platelets, cells that play a major role in the blood clotting process, but sildenafil appears to have no direct impact on platelet function. However, the drug’s effects have not been specifically evaluated in patients with bleeding disorders or in those taking drugs that reduce clotting.
“Experimental and human studies indicate that PDE-5 inhibitors are effective and well tolerated, and there is evidence that they are not being used to their utmost potential. We suggest that these drugs may prove beneficial in treating a wide variety of disorders,” said Schwarz, the article’s first author and a specialist in cardiology, interventional cardiology, heart failure, and transplantation. “Some studies are underway to determine the effects of long-term use of PDE-5 inhibitors, and others are warranted, especially in patients who are considered at high risk because of chronic cardiovascular disorders.”
Their findings appear in the June 8, 2006 issue of the International Journal of Impotence Research.
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