Matthew Herper, 09.24.07

You wouldn’t know it from the lack of fanfare, but the Food and Drug Administration is getting its biggest overhaul in a decade in a dramatic coda to Merck’s withdrawal of the blockbuster painkiller Vioxx three years ago.

A bill to give the FDA more power passed both houses of Congress with only a handful of no votes, and the president is expected to sign it into law. Because the bill is attached to the re-authorization of an important part of the FDA’s funding, a veto is unlikely. If the law doesn’t pass soon, FDA head Andrew Von Eschenbach is going to have to start informing staffers that their jobs are no longer funded.

The bill represents a victory for advocates of higher standards for making sure that drug side effects are known and promptly dealt with. Before Vioxx was yanked, some of the changes being made would be unimaginable. Until now the claims drug companies like Merck and Pfizer made about their medicines were, to a degree, negotiated. Labeling discussions between Merck and the FDA dragged on, and as a result, the agency will now be able to dictate what claims companies can make with much more force.

Another change: The FDA will be able to force drug makers to do clinical trials even after a medicine is approved and fine them if they don’t follow through. Previously, many big clinical trials regulators asked for weren’t finished. And there will be more money to study side effects of new medicines post-approval. Companies will pay more in fees when they submit drug applications, increasing the amount of money the FDA gets from industry by 25% to $400 million.

One of the farthest-reaching changes may be a new requirement demanding that the drug companies list all of their clinical trials in a registry maintained by the National Institutes of Health accessible to anyone with an Internet browser. After the studies finish, the results will also have to be posted. This will expose drug companies to new levels of scrutiny about the safety of their medicines. (See: Lynch ‘Em)

Rough-and-ready analyses of existing data set off the Vioxx controversy and the recent kerfluffle over the diabetes drug Avandia. Such analyses, where researchers try to combine different studies to get a better idea of what kinds of side effects emerge in incredibly large groups, also linked antidepressants like GlaxoSmithKline’s Paxil to suicide risk and the Johnson & Johnson heart failure medicine Natrecor to kidney problems. In both cases, there are still debates about how real the risks are, but they put a squeeze on sales.

Lots of stuff didn’t go into the bill. The Union of Concerned Scientists, while lauding the bill, worried that it didn’t do enough to deal with the financial conflicts of FDA advisers. It appears to only increase the FDA’s power to regulate direct-to-consumer ads a little bit. Pharmaceutical companies had at one point hoped that the bill would contain language that helped protect products that had been vetted by the FDA from product liability suits.

At one point, it looked as if the bill might address how the FDA should go about approving cheaper copycat versions of biotech protein drugs like insulin and human growth hormone. Right now, there’s no mechanism for approving true generics of these products, which can be extremely expensive. Part of the reason: Complex safety issues arise because proteins are far more difficult to manufacture than the simpler chemicals in pills like Vioxx and Lipitor.

But all of these issues were Johnny-come-latelies to the Congressional debate. The focus was creating a more transparent FDA with the power to better study and regulate drug safety. Legislators were probably smart, in the end, to stick with the issues they had debated the most and approve a bill that is uncontroversial now but would have seemed like a radical step three years ago.

Hopefully, the changes will strengthen the FDA, renewing the public’s shaken faith in the safety of medicines. Drug makers could wish for nothing more.

Science Daily — Researchers report that fasting or eating half as much as usual every other day may shrink your fat cells and boost mechanisms that break down fats.

Consuming less calories and increasing physical activity is usually what people do to lose weight and stay healthy. But some people prefer to adopt a diet which consists of eating as much as they want one day while fasting the next. On each fasting day, these people consume energy-free beverages, tea, coffee, and sugar-free gum and they drink as much water as they need.

Although many people claim that this diet, called alternate-day fasting (ADF), help them lose weight and improved their health, the effects on health and disease risk of ADF are not clear.

Krista Varady and colleagues studied the effects of alternate-day fasting on 24 male mice for four weeks. To assess the impact of ADF on the health of the mice, the scientists not only tested mice that followed and didn’t follow an ADF diet, but they also studied mice that followed the diet only partially: a group of mice consumed 50 percent of their regular diet every other day (ADF-50%) and another consumed 75 percent of their regular diet every other day (ADF-25%).

The scientists noticed that the ADF-100% mice lost weight and the fat cells of both the ADF-100% and ADF-50% groups shrunk by more than half and by 35 percent, respectively. Also, in these two groups of mice, fat under the skin — but not abdominal fat — was broken down more than in mice that did not follow the diet.

These results suggest that complete and modified ADF regimens seem to protect against obesity and type 2 diabetes but do not result in fat or weight loss. More studies will be needed to confirm whether the long-term effects of ADF regimens are beneficial for health and reduce disease risk, the scientists conclude.

Article: “Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism and plasma adiponectin levels in mice,” by Krista A. Varady, D. J. Roohk, Y. C. Loe, B. K. McEvoy-Hein, and M. K. Hellerstein

Note: This story has been adapted from a news release issued by American Society for Biochemistry and Molecular Biology.

Science Daily — Administering hydrogen sulfide (H2S) directly into the heart during a simulated heart attack significantly reduces the tissue and cell damage often seen in oxygen-starved organs, according to a new study from researchers at the University of Alabama at Birmingham.

H2S boosts post-heart-attack function by helping to minimize reperfusion injury, an unwanted side effect of restoring blood flow swiftly to hearts suffering from low oxygen, the study authors said.

In testing on mice, the H2S injection led to a 72 percent reduction in the amount of severe heart-tissue death after restoring normal oxygen and blood flow to mice hearts. The 72 percent reduction compares to a much larger average amount of tissue death in un-treated mice hearts after the same 30 minutes of oxygen deprivation.

Findings on the protective qualities of H2S have broad implications for improving human survival after cardiac arrest, heart transplant and trauma in general, said David Kraus, Ph.D., a UAB associate professor in the Departments of Environmental Health Sciences and Biology and co-author on the new study.

“One of the most damaging biological stresses on the heart and other organs from trauma or transplantation is the rapid change in oxygen levels,” Kraus said. “First there’s a drop, which elicits a dramatic cellular adjustment to survive low oxygen, and then a rapid rise caused by resuscitation.

“H2S as an internal bodily signal appears to serve as an important protective mechanism during the stress of low oxygen availability,” he said.

The UAB researchers worked with a team led by David Lefer, Ph.D. from the Albert Einstein College of Medicine in Bronx, N.Y.

The tests were done by injecting H2S directly into the hearts of mice who had been anesthetized for surgery, and whose left ventricular artery had been clamped for 30 minutes to simulate a heart attack.

In addition to a decrease in heart-tissue death, H2S-treated mice hearts showed a 35 percent drop in blood-protein levels that signal myocardial damage, and a 26 percent drop in heart-tissue markers of inflammation when compared to un-treated mice hearts.

Furthermore, by isolating mitochondria from the H2S-treated mice, the authors confirmed that heart-cell functional integrity had been preserved. Recent reports from other researchers demonstrate that inhaled H2S can induce a fully reversible “suspended animation” state in animals.

Kraus said it follows that H2S could be used to place organs into “suspended animation” before surgery or during medical transport until normal oxygen and blood flow is restored. Also, by augmenting internal H2S production in the body, perhaps through diet, people may reduce their risks of cardiovascular disease, chronic oxidative cell damage and other illnesses, Kraus said.

H2S is normally considered a toxic, flammable gas that is responsible for the foul odor of rotten eggs. But in the UAB study it was carefully formulated into a low concentration saline-type solution.

The study was published Sept. 18 in the online Early Edition of the journal Proceedings of the National Academy of Sciences. It also included researchers at Thomas Jefferson University in Philadelphia, the University of Medicine and Dentistry of New Jersey and the National Institute of Neuroscience in Tokyo, Japan. Grant support came from the National Institutes of Health, the American Diabetes Association, the American Heart Association and from Ikaria Inc. in Seattle, Wash. This story has been adapted from a news release issued by University of Alabama at Birmingham.