|Selected news articles which highlight important policy issues.||
News: Weekly Archives
News for the week of 09-05-2005
Online Extra: Putting the FDA Out Front
Here’s some wisdom from Woodcock. Thanks Janet. Hopefully words presage deeds!
Vioxx trials to pain industry
At a recent legal seminar on the litigation surrounding Vioxx one personal injury attorney argued that if “Merck had been forthcoming about Vioxx and did a true clinical trial on the cardiovascular risks, the drug might still be on the market for a limited number of consumers.” Ironically, companies have few incentives to conduct such studies, largely thanks to America’s system of jackpot justice.
How safe is it for pharmaceutical companies to study the safety of their products? Very unsafe. All the incentives point the other way. It is impossible to know all of the risks associated with a drug before it is marketed, and any study risks exposing the manufacturer to crushing tort liability—as Merck is discovering. Companies, consequently, have a responsibility to their shareholders to walk a fine line between studying the benefits of their medicines and accurately conveying known risks to patients and physicians.
Instead of relying on self-serving attorneys and fickle juries to regulate the nation’s drug supply, we should institute an administrative compensation system for drug side effects along with “safe harbor” from punitive damages for companies that comply with FDA regulations and report safety concerns in a timely manner. This would encourage companies to look more proactively at safety data than they now do.
The bottom line, however, is that patient interests aren’t best served by elevating safety to the be-all and end-all of pharmaceutical research. As law professor Rebecca S. Eisenberg argues in a recent editorial in the New England Journal of Medicine
Studies testing efficacy and safety are more informative than those testing safety alone; indeed, it is difficult to make sense of the concept of safety apart from the vantage point of particular patient populations and therapeutic goals. To rank safety ahead of efficacy seems to miss the obvious point that patients may be harmed by disease as well as by drugs.
The current litigation climate, however, encourages plaintiff’s attorneys to put the drug, not the disease, on trial, thereby demonizing the pharmaceutical industry and inhibiting valuable medical research. This is certainly one side effect of our tort system that we can live without.
Pfizer Inhalant Drug For Diabetics Wins Support of FDA Panel
No life-saving medicine in the world is any good unless patients can be convinced to use it correctly and consistently. Consequently, last week’s vote by an FDA advisory committee to recommend FDA approval for a new type of inhaled insulin may represent a significant improvement in diabetes treatment—even if the drug is not, in the abstract, any more powerful than existing therapies.
Americans idealize physicians. And so it is easy to forget that patients play a critical role in maintaining their own health, particularly when it comes to chronic diseases like diabetes, which require daily management. Estimates of patient noncompliance in diabetes treatment vary, but everyone seems to agree that they are far too high. As a result, companies are constantly trying to design drugs that are easier for patients to self-administer:
A Food and Drug Administration advisory committee recommended approval for Pfizer Inc.'s Exubera, the first inhaled version of insulin and a potential sales blockbuster that could significantly change the treatment of diabetes.
The panel voted 7-2 in favor of the product despite worries about its effects on the lungs, a decision that will reassure a pharmaceutical industry concerned about how the FDA and its advisers weigh safety in drug reviews. …
The panel supported Exubera's use in both Type 1, or so-called juvenile, diabetes, and Type 2, sometimes called adult-onset, diabetes. There are about 18 million diabetics in the U.S., and the number is rising. Pfizer argued that many diabetics don't currently get optimal treatment, and that a new option that cuts down the need for insulin injections might convince patients to better adhere to recommendations to keep their blood sugar under control.
"It was shown to be as effective as current therapy, and it's an important new modality that will probably help some patients comply better" with treatment recommendations, said Talmadge King, a panel member who is a professor at the University of California at San Francisco. Rebecca Killion, a patient representative on the panel, said diabetics will find the new option appealing as an alternative to needles.
As we mentioned earlier in our discussion of PPAR drugs, diabetes is a disease that unless it is carefully controlled can lead to a variety of other serious health concerns that make treatment even more difficult and drive up health care costs. The FDA advisory committee’s recommendation that the FDA approve this version of inhaled insulin is a welcome sign that the FDA’s outside experts recognize that the vehicle for delivering a therapy can be as important for maintaining health as the therapy itself.
Diabetes Drug Cuts Heart Attacks
Diabetes is not just about blood sugar. It is a syndrome that affects the entire body and can lead to other devastating illnesses unless it is carefully controlled. According to the American Diabetes Association, “2 out of 3 people with diabetes die from heart disease and stroke”.
In fact, there is a desperate need for new medicines that not only control diabetic blood sugar, but can also reduce associated risk factors for heart disease, stroke and obesity. Thankfully, several new drugs in development—and another one already on market-- may revolutionize the treatment of diabetes and its related morbidities.
The ADA notes that
Studies have shown that up to 60% of adults with diabetes have high blood pressure and nearly all have one or more lipid abnormalities, such as increased triglycerides, low HDL cholesterol, or elevated LDL cholesterol. While the management of blood sugar has always been and remains a cornerstone of diabetes care, diabetes requires a comprehensive program that includes management of blood glucose, management of blood pressure and management of cholesterol.
Pharmaceutical companies are racing to develop drugs that target “one set of three related genes that might be able to combat [obesity, diabetes and heart disease]” simultaneously. The genes are called “peroxisome proliferators activator receptors, PPARs,” and are identified as alpha, gamma, and delta PPARs. Current generation PPAR drugs are thought to hit only one of these genes at a time. Newer drugs, like Pargluva (pending FDA approval), “work on combinations.”
PPAR alpha reduces the risk of heart disease and is the target of drugs like TriCor, from Abbott, and Lopid, from Pfizer… One study showed Lopid cut heart attacks by 22%. PPAR gamma is one of the most important genes linked to diabetes and is the target of Actos. Patients with a mutated version have a 25% higher risk of developing adult-onset diabetes. PPAR delta makes mice lean and muscular and may prevent heart disease, but no marketed medicines take advantage of it.
Pargluva passed muster with an FDA advisory committee last week—although the FDA does not have to follow the recommendations of its advisory committees, and there are some concerns about potential side effects. An older drug already on the market, Actos, may turn out to suppress multiple PPAR genes as well:
A new three-year study of 5,200 diabetics shows that Actos, a popular drug for helping control blood sugar, also prevents heart attacks, strokes and death in diabetics.
"This is the first time that an oral diabetic medicine has been shown to have this benefit in a prospective study," said John Dormandy, of St. Georges Hospital in London, who headed the trial. Patients in the study received cholesterol and blood-pressure lowering medicine, and other therapies as well, in both the placebo and Actos groups. 'It's a good result, but we need more studies to confirm this strategy," Steven Nissen said, a cardiologist at the Cleveland Clinic.
The difficulty facing companies and regulators is that PPAR drugs “have a mixed safety record.” Nonetheless, given the immense damage these diseases inflict on American health, the search for more effective PPAR drugs is well worth the risk.
Cancer prevention studies involving Celebrex resume
COX-2 drugs like Vioxx may yet prove to be vital weapons in the war on cancer. Unfortunately, the unmitigated media and legal assault on the entire COX-2 class has overshadowed their value and continues to hinder research into their anti-cancer properties.
Treating cancer after its symptoms have become apparent—when the disease may be advanced or has even metastasized—is notoriously difficult. Cancer researchers, consequently, are increasingly looking to beat the disease to the punch, and prevent the biochemical changes that turn normal cells into ticking time bombs, a strategy called chemoprevention.
Before revelations about Vioxx’s cardiovascular risks shut down dozens of clinical trials, COX-2 drugs like Vioxx, Celebrex, Bextra were being widely studied for their ability to prevent certain cancers (like lung and colon cancer) that over-express the COX-2 enzyme. While Vioxx and Bextra remain off the market, the National Cancer Institute and the FDA are encouraging researchers to continue chemoprevention trials with Celebrex, which is widely considered to have a lower cardiovascular risk profile than those other drugs.
Lab studies have shown that an enzyme blocked by Celebrex may trigger inflammation that could play a role in developing lung cancer…
In February, the U.S. Food and Drug Administration recommended that researchers keep studying Celebrex's cancer-prevention potential, and the National Cancer Institute encouraged researchers to weigh its risks and benefits in their clinical trials. …
M.D. Anderson's [Celebrex] study [of cigarette smokers taking the drug] was two-thirds complete when it was suspended. Researchers cut its length to six months from a year and ordered blood pressure monitoring with aggressive treatment for any cardiovascular changes. Also, no patients who have had heart attacks or strokes can participate. [Dr. Bernard Levin, M.D. Anderson’s vice president of cancer prevention] said that [the] reduced pool of potential patients -- as well as general concern about potential heart dangers of Cox-2 inhibitors -- could hinder recruitment efforts. "Likely this will take longer than intended," he said.
Vioxx is a drug with real risks, but it is not the killer that the media and plaintiff’s bar have made it out to be. Unfortunately, because of the public animus against COX-2 drugs, it may take researchers years longer to unravel their potential to prevent fatal cancers.
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