Drugs Log

US drugmakers Pfizer Inc and Nektar Therapeutics on Wednesday warned of cases of lung cancer in clinical trials of their inhaled insulin Exubera.

The findings led Nektar to announce it was abandoning its search for a new marketing partner for the troubled drug, effectively signaling Exubera’s demise after entering the market in January 2006.

Pfizer, the world’s largest pharmaceutical company, announced last October it stopped marketing Exubera, saying it did not meet customer needs or the financial expectations of the company.

The rise in lung cancer apparently linked to Exubera led Pfizer to update the medication’s warning label to include information “about lung cancer cases observed in patients who used Exubera,” the company reported in a statement.

It said that over the course of the clinical trial, six out of 4,740 Exubera-treated patients developed lung cancer, versus one of the 4,292 patients not treated with Exubera.

An additional case of lung cancer in an Exubera-treated patient was discovered after the drug’s debut on the market following its approval by the US Food and Drug Administration.

The updated label states that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were “too few cases to determine whether the development of lung cancer is related to the use of Exubera.”

“Some patients continue to take Exubera, including those enrolled in extended transition programs or clinical trials,” Pfizer chief medical officer Joe Feczko said in the statement.

“We are working closely with patients and their physicians to ensure the continued orderly transition from Exubera to alternative therapies,” he added.

Nektar announced it was stopping all spending on the drug, including research and marketing.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Nektar president Howard Robin on the company’s website.

Diabetes affects 230 million people worldwide, including 21 million in the United States, according to Pfizer. Exubera is a short-acting insulin breathed in through an inhaler that helps control high blood sugar in people with diabetes.

Pfizer warns Exubera patients about risk

Pfizer Inc. said Wednesday it is warning patients using its inhaled insulin product Exubera about the risk of lung cancer, leading Nektar Therapeutics to terminate its inhaled insulin programs.

Nektar had been Pfizer’s partner on Exubera from 1995 until Pfizer discontinued the drug in October 2007 after lackluster sales. Some patients continue to take the drug, however, including some enrolled in extended transition programs or clinical trials.

On Wednesday, Pfizer said it updated the U.S. product labeling for Exubera Inhalation Powder to include a warning about lung cancer cases observed in patients who used the inhaled insulin treatment.

Over the course of Exubera’s clinical trial program, 6 of the 4,740 patients treated with Exubera developed lung cancer, compared with 1 of the 4,292 patients not treated with the drug.

There was also a post-marketing report of lung cancer in one Exubera-treated patient.

The label notes that all patients who developed lung cancer had a prior history of cigarette smoking, and that there were too few cases to determine whether the cancer is related to use of Exubera.

Pfizer said the data was reviewed by the company and the Food and Drug Administration.

Nektar said it will stop all spending associated with its inhaled insulin programs and will not incur any additional charges related to the action.

“The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners,” said Howard W. Robin, president and chief executive of Nektar, in a statement. “Fortunately, over the past year Nektar has significantly transformed its business, moving away from inhaled insulin.”

Exubera

Generic Name: insulin inhalation
Brand Names: Exubera

What is Exubera?

Insulin inhalation (Exubera) was withdrawn from the U.S. market in 2007 due to lack of consumer demand for the product. No drug safety concerns were cited in this withdrawal.

Exubera is a rapid-acting form of human insulin that is inhaled through the mouth. It works by lowering levels of glucose (sugar) in the blood.

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Ten years ago this month the lives of millions of men and women were changed almost overnight by the advent of a little blue pill — the first oral treatment for impotence.

Viagra, developed by accident by scientists at Pfizer Laboratories, was first approved for use by the US Food and Drug Administration on March 27, 1998.

“Originally, we were testing sildenafil, the active drug in Viagra, as a cardiovascular drug and for its ability to lower blood pressure,” said Dr Brian Klee, senior medical director at Pfizer.

“But one thing that was found during those trials is that people didn’t want to give the medication back because of the side effect of having erections that were harder, firmer and lasted longer.”

Since Viagra went on the market it has been used by 35 million men around the globe, and it took impotence off the taboo list, making it infinitely easier to treat.

Urologists’ waiting rooms became busier as news got round that the condition, which was rechristened with a new, scientific name — erectile dysfunction, or ED — could be treated with a triangular blue pill.

Previous treatments had involved surgically inserting a prosthesis into the penis, injecting a substance into the male sex organ or using urethral suppositories.

“Viagra brought a lot more people into the office because of the ease of treatment,” Dr Irwin Shuman, a urologist of 40 years’ experience in Washington, told AFP.

“In the old days, when we didn’t have much in the way of treatment, we would do a lot more evaluation, looking for answers as to why somebody had the problem,” he said.

In one test, men would be observed while sleeping to see if erections occurred.

Men who failed to get the usual five to six erections per night were deemed to have a physical problem, and those who did get nocturnal erections were said to have a psychological problem and were sent to see a sex counsellor.

So Viagra helped move impotence out of the psychological realm and into the world of physical illnesses. “What we have come to understand in the past 10 years is that ED is a vascular disease,” said Klee.

“What happens is veins and arteries that deliver and remove blood from the penis are not working the way they should, and Viagra allows those vessels to dilate and increase blood flow to the penis,” he said.

Dr Abraham Morgentaler, director of Men’s Health Boston, and associate clinical professor of urology at Harvard Medical School, hailed Viagra as a “benefit to medicine.”

But, he added, the drug has not delighted all those who took it.

“There are two truths to Viagra: for those who refill (get a new prescription), it’s wonderful and they’re happy,” Morgentaler told AFP.

“But a lot of people look to Viagra for personal happiness, thinking a hard penis can resolve relationship issues,” and they end up disappointed, added the doctor and author of the book “The Viagra Myth.”

Some patients say taking Viagra “does not correspond to the way they want to have sex,” Morgentaler said.

Viagra works best on an empty stomach or after eating a low-fat meal, the medication’s official website says. It kicks in about 30 minutes after being taken, works for four hours, and only with sexual arousal, the website says.

But it’s not the answer for everyone. Morgentaler said he had a 78-year-old patient in his office who “didn’t like the idea of programming sex. Guys, and often women, too, don’t necessarily want to compromise the ideal of sex as something magical, spontaneous, romantic.”

Morgentaler also spoke of the darker side of Viagra, which has evolved since it and two other ED treatments became easily available over the Internet.

“It’s the use of Viagra by healthy young men who don’t need it,” he said.

“These young men take a pill whenever they go out … Maybe because they are inexperienced or shy and Viagra makes them more confident, or maybe because they have inflated ideas about what sex is supposed to be like from seeing Internet porn, which they also have easy access to, and they want to heighten their feelings of masculinity,” he said.

“I am concerned — not that these young men will get addicted physically, but that they will become psychologically dependent on Viagra,” said Morgentaler.

“Sex is an entree into a relationship, and most often what we want from a relationship is to be loved for what we are.

“But some of these young men feel they have to take a pill to be acceptable, and I fear they are potentially missing the opportunity to have true emotional connections with a partner, based on reality, not mythology.”

Viagra celebrates its 10th birthday

The potency enhancing drug Viagra has been on the market for 10 years. In 1998, pharmaceutical company Pfizer introduced the erection drug that was to change millions of lives at a stroke. A solution to erectile dysfunction had been found, and the taboo surrounding impotence was largely a thing of the past.

The little blue pill that enabled millions of couples to reawaken their sex lives was discovered by accident, says sexologist Vera Steenhart of the Dutch Sexology Association. Pfizer was actually looking for a drug for the heart problem angina pectoris. The pills didn’t appear to be benefiting the test subjects, but they refused to give them back. Ms Steenhart:

“The manufacturers found this strange. On further investigation, they found the drug gave the male patients an erection. They were extremely happy about it.”

Effect
The forerunner to Viagra was developed to make blood vessels relax. The test subjects were given the drug to improve blood circulation to the heart to reduce the chance of heart failure. Viagra has the same effect on the penis. When the man is sexually stimulated, the blood supply is improved and it becomes easier for him to maintain an erection.

It’s a myth that the pill can produce an unwanted erection. The user does actually have to be in the mood, so Viagra has little or no effect if he is unwilling to have sex or feels anxious about it. In that case it would be more appropriate for him to have a good talk with his partner or pay a visit to a psychologist or sexologist.

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Patients who receive free drug samples from their doctors end up having significantly higher out-of-pocket costs for their prescription drugs than people who don’t receive free samples, a new study finds.

In fact, patients who received free samples spent about $166 in out-of-pocket costs on prescription drugs in the six months before receiving the samples, $244 for the six months in which they received samples, and $212 for the six months following receipt of the free drugs, the study found.

But patients who didn’t get free samples spent about $178 on prescription drugs over six months.

“This is a curious finding because one would think, intuitively, that if you receive a free sample, one’s out-of-pocket prescription cost would be lower, not higher,” said lead researcher Dr. G. Caleb Alexander, an assistant professor of medicine at the University of Chicago Medical Center.

There are several possible explanations for the finding, Alexander said. One is that patients who receive free samples may be sicker than patients who don’t get samples.

“The second possibility is that patients who receive free samples may go on to receive and fill prescriptions for the very same medicine that were initially begun as free samples,” Alexander said. “We know that drugs that are available as free samples are those that are being widely marketed and promoted and these drugs are more expensive than their older, less promoted counterparts.”

The study findings are published in the March 24 issue of the journal Medical Care.

For the study, Alexander’s team collected data on 5,709 patients who had participated in the Medical Expenditure Panel Survey. The survey was done by the U.S. Agency for Healthcare Research and Quality and the patients were followed for up to two years.

Seventy-six percent of the patients had private health insurance. During the study period, 14 percent of them were given at least one drug sample. A total of 2,343 samples were distributed during the period, the researchers found.

Patients who received free samples were more likely to be younger and have private insurance, while patients with Medicaid were less likely to receive samples, the researchers noted.

The findings follow earlier research, reported in the February issue of the American Journal of Public Health, in which Harvard University researchers showed that more than 80 percent of free drug samples were given to wealthy and insured patients, not to uninsured and poorer patients.

Alexander said there are many ways doctors and patients can work together to reduce drug costs, but giving away free samples may not be the best one.

“Doctors and patients both should be encouraged to consider alternative ways to reduce patients’ out-of-pocket costs,” he said. “There are many other strategies doctors can use, such as prescribing a three-month rather than a one-month supply, such as using greater numbers of generic medicines, and discontinuing non-essential medicines.”

Dr. David Katz, director of the Yale University School of Medicine’s Prevention Research Center, said free samples aren’t designed to help lower drug costs, but rather to sell newer and more expensive drugs.

“Almost every clinician’s office is stocked with drug samples,” he said. “For patients and providers alike, these free drugs can take on the aura of Halloween goodies. Passing them out feels like giving a gift.”

But, Katz added, “free samples are by no means a long-term solution to high prescription drug costs. Rather, they are at least, in part, a marketing device, a chance to sample the wares.”

The pharmaceutical industry had this to say: “Free pharmaceutical samples are beneficial to patients of all income levels. Patients are able to try out a new therapy - gaining valuable first-hand experience of its benefits and side effects - without making a co-payment,” said Pharmaceutical Research and Manufacturers of America (PhRMA) senior vice president Ken Johnson.

“What’s more, contrary to statements made by critics, America’s physicians prescribe medicines based on a wide range of factors, not simply receipt of free prescription drug samples,” Johnson added in a prepared statement.

Free Drug Samples? Bad Idea, Some Say

Everyone loves freebies, and patients are no exception. So drug company sales representatives try to keep sample cabinets in medical offices well stocked with the latest medications, for doctors to dispense as the need arises.

Patients like going home with free samples because it saves them a trip to the drugstore and a co-pay, and doctors are happy to oblige, because samples help patients get started on treatment right away.

But now some leading academic medical centers are restricting the use of samples, and a smattering of physician practices are shutting down the sample cabinet. These critics say doctors should be choosing the most appropriate medication for a patient based on the best scientific evidence available — not just grabbing something from the office stash that happens to fit the bill.

“The doctor will say, ‘Here, start on this, and let’s see how it works,’ ” said David J. Rothman, president of the Institute on Medicine as a Profession, a research group at Columbia. “The question to the doctor is: If you didn’t have it in your drawer, would that have been your drug of choice?”

The crackdown on free samples comes amid growing concern about the close ties between physicians and drug companies. Critics like Dr. Rothman say physicians don’t realize the extent to which their medical judgment is influenced by their acceptance of the samples. They point to studies like a 2002 paper in the journal Annals of Family Medicine finding that the number of doctors who treated high blood pressure with the “first line” drugs recommended by national guidelines was low, but increased sharply when free samples were removed.

So far, the University of Michigan Health System has banned free samples altogether, and the University of Pennsylvania and Stanford University medical schools have prohibited staff members from accepting them (though samples can be given to Stanford’s pharmacy for use in free clinics).

Some medical groups and solo practitioners have also changed their policies. Dr. Jonathan Mohrer, an internist in Forest Hills, Queens, said he closed his sample cabinet in part because his office was overrun with sales representatives. “It was totally spinning out of control,” Dr. Mohrer said. “They were meeting each other and schmoozing in the waiting room — it was like a party.”

His office staff had to spend time arranging the cabinet, throwing out expired medications and rummaging around for the right drug. Patients were kept waiting while sales representatives were whisked in.

But there’s an upside to the samples. Using samples, a doctor can see if a patient can tolerate a new medication before the patient goes out and buys a 30-day supply. Physicians who treat poor people like to have samples on hand for them, and for uninsured patients.

Samples also provide patients with the convenience of one-stop shopping, said Dr. Hema A. Sundaram, a dermatologist in suburban Washington. “Usually a patient has waited some time to see a doctor and rearranged their whole working schedule, and then it may be another four or five days before they can fill a prescription,” she said. “They’re often busy, working people, with family responsibilities. I feel there shouldn’t be any further delay.” (Dr. Sundaram acknowledges that she is paid for speaking on behalf of drug companies.)

And many physicians say they like using samples because the sales representatives are an important source of medical education, helping to keep the doctors up to date on the latest therapies.

“Doctors who are shutting the door to sales reps are cutting themselves off from a lot of valuable information,” said Scott Lassman, senior assistant general counsel for the Pharmaceutical Research and Manufacturers of America, a trade association. “Sales reps can explain when it’s right to use a drug, when it’s not right to use the drug, which patients might benefit and which patients it might not work for.”

Some doctors are skeptical. “The sales reps are nice people, and they try to do a really good job,” said Dr. Judith Chamberlain, medical director of the Bowdoin Medical Group, a practice near Portland, Me., that banned samples this year. “But their job is to get you to use their product.”

A 1995 study in The Journal of the American Medical Association found that 11 percent of the statements drug company representatives made during presentations were inaccurate, and all of the inaccuracies were skewed in favor of their products.

The drugs promoted through free samples tend to be the newer medications that doctors are less familiar with, experts say. Some critics of samples say they prefer using older drugs anyway, because their side effects are better known. Critics also point out that helping poor and uninsured patients is not the intent of the sample distribution, and they add that developments like Medicare’s prescription-drug coverage, the proliferation of generic drugs and improvements in drug company patient-assistance programs have eased access to medication.

As for the bottom line, it’s not at all clear that samples save patients money. Critics say they may actually drive up the cost of health care in the long run, because the drugs being promoted are the most expensive brand-name medications. Since many conditions require lifelong treatment, the patient would have to buy the medicine sooner or later.

“You’re going to be paying more, because you’re taking the new, advanced drug,” Dr. Rothman said. “And you may have done just fine on the old-fashioned generic.”

Do free drug samples influence residents’ prescribing decisions?

When a pharmaceutical company puts drug samples into the hands of residents as a form of marketing, how does it influence their prescribing behavior? To what extent are treatment decisions based on which samples are available and further, what are the implications for patient care as well as resident education? While this is a frequently debated issue, there has been little objective data describing how drug samples affect resident physicians. In a study published in the August issue of The American Journal of Medicine, researchers from the University of Minnesota and Abbott Northwestern Hospital conducted a randomized study of 29 internal medicine residents over a 6-month period in an inner-city primary care clinic. Highly advertised drugs were matched with drugs commonly used for the same indication that were less expensive, available over-the-counter, or available in generic formulation. By random selection, half of the residents agreed not to use available free drug samples. The authors observed 390 decisions to initiate drug therapy in five drug class pairs.

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In the latest research to cast a shadow on the safety of a popular bone-strengthening medication, researchers report that long-term use of Fosamax is associated with unusual fractures of the thigh bone.

The fractures were low-energy fractures, meaning that they all occurred from a fall from standing height or less, and the bone cracks were in an unusual horizontal pattern. About one-third of women with these types of fractures were on long-term therapy to prevent osteoporosis, the researchers noted. Of these women, two-thirds were taking Fosamax (alendronate), for an average of more than seven years.

Fosamax is a bisphosphonate, a class of drugs used to increase bone mass and reduce the risk of fracture in those who have osteoporosis.

“These were peculiar fractures that would occur when the women were basically doing nothing,” said the study’s senior author, Dr. Joseph Lane, chief of metabolic bone disease at the Hospital for Special Surgery at Weill Cornell Medical College in New York City.

Fifteen women were included in Lane’s analysis. The average time on Fosamax was 5.4 years before they experienced the unusual femur fracture. Of these 15, 10 women had similar, atypical fractures. These women had been taking Fosamax for an average of 7.3 years, while the remaining five had only been on the drug for an average of 2.8 years.

“Our results provide further evidence of a potential link between alendronate use and low-energy fractures of the femur,” the authors said in a letter reporting their findings, which is published in the March 20 issue of the New England Journal of Medicine. But, the authors acknowledge the limitations of their retrospective analysis and suggest that these findings need to be confirmed in a prospective study.

Lane said there are several theories as to how alendronate could be related to these fractures. One is that the drug slows down the development of new collagen, and he said new collagen is very strong. Another could be because there is slower bone turnover on the medications. That could mean there may be accumulated microdamage in the bone, making it more susceptible to fracture in certain women.

Lane said that women taking this medication should keep taking it, and these findings shouldn’t cause them alarm. “This is a great drug that does wonderful things. Bisphosphonates have dropped the rate of hip fractures,” he added.

Ron Rogers, a spokesman for Merck, which manufactures Fosamax, said, “Fosamax has not been associated with an increased risk of fracture at any skeletal site.” Rogers also noted that this study didn’t prove a cause and effect relationship between the drug and these unusual fractures, and that the researchers noted that 63 percent of women treated for low-energy fractures weren’t taking bisphosphonates at all.

Dr. Loren Wissner Greene, co-director of the osteoporosis and metabolic bone disease program at the New York University School of Medicine, agreed that this study has just pointed out an association between Fosamax use and these fractures, not proven a causal relationship.

Still, Greene said she believes these atypical breaks probably are related to the medication, although she added, “If this is a related complication, it appears to be very rare.”

Like Lane, she said, “Alendronate is still a very valuable drug in decreasing the risk of hip fracture.” But, she said, what would be helpful is a test that could identify who is in the sub-population that might have a problem on this medication.

Lane said that women who’ve been taking this medication for a long time and have test results that suggest low bone turnover, may want to take a “bone holiday,” and stop taking the medication for a year. But, he added, this shouldn’t be done on your own. “If you’ve been on alendronate for a long time, talk to your doctor,” he suggested.

The U.S. Food and Drug Administration in January issued an alert to physicians about the possibility of severe bone pain occurring as a result of bisphosphonate therapy. Additionally, last year Fosamax was also implicated in some cases of atrial fibrillation — a serious type of irregular heartbeat — though the FDA hasn’t found evidence to support this association.

Fosamax

Generic Name: alendronate

What is the most important information I should know about Fosamax?

Do not take an Fosamax tablet if you cannot sit upright or stand for at least 30 minutes. Fosamax can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication.

Take the Fosamax tablet first thing in the morning, at least 30 minutes before you eat or drink anything or take any other medicine.
Take each dose with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water) when taking an Fosamax tablet.

For at least the first 30 minutes after taking an Fosamax tablet, do not lie down or recline; do not eat or drink anything other than plain water; and do not take any other medicines including vitamins, calcium, or antacids.

Some people using medicines similar to Fosamax have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms of this condition may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.

Fosamax is only part of a complete program of treatment that may also include diet changes, exercise, and taking calcium and vitamin supplements. Follow your diet, medication, and exercise routines very closely.

What is Fosamax?

Fosamax is in the group of medicines called bisphosphonates (bis FOS fo nayts). It alters the cycle of bone formation and breakdown in the body. Fosamax slows bone loss while increasing bone mass, which may prevent bone fractures.

Fosamax is used to treat or prevent postmenopausal osteoporosis and steroid-induced osteoporosis. Fosamax is also used to treat Pagets disease of bone.

Fosamax may also be used for purposes other than those listed in this medication guide.

What should I avoid while taking Fosamax?

Do not take any other medicines including vitamins, calcium, or antacids for at least 30 minutes after taking an Fosamax tablet. Do not lie down for at least 30 minutes after you take an Fosamax tablet.
What are the possible side effects of Fosamax?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using Fosamax and call your doctor at once if you have any of these serious side effects:

• chest pain;
• difficulty or pain when swallowing;
• pain or burning under the ribs or in the back;
• new or worsening heartburn;
• severe joint, bone, or muscle pain; or
• jaw pain, numbness, or swelling.

Continue using Fosamax and talk with your doctor if you have any of these less serious side effects:

• mild heartburn or stomach upset;
• diarrhea, gas, or constipation;
• joint pain or swelling;
• swelling in your hands or feet;
• back pain; or
• dizziness, weakness, or headache.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Fosamax?

Antacids, supplements, or medicines that contain aluminum, calcium, magnesium, or other minerals can interfere with how your body absorbs Fosamax. If you use these other medicines, do not that take them for at least 30 minutes after taking an Fosamax tablet.

Before using Fosamax, tell your doctor if you also use aspirin or other NSAIDs (non-steroidal anti-inflammatory drugs) such as celecoxib (Celebrex), diclofenac (Voltaren), diflunisal (Dolobid), ibuprofen (Motrin, Advil), indomethacin, ketoprofen (Orudis), ketorolac (Toradol), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others.

There may be other drugs that can affect Fosamax. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

The European Commission has referred GlaxoSmithKline Plc’s breast cancer treatment Tyverb back for a fresh assessment by drugs regulators following new data from Europe’s biggest pharmaceuticals company.

Glaxo said on Tuesday that Tyverb, which is already on sale in the United States under the name Tykerb, had been referred back to the EU’s Committee for Medicinal Products for Human Use (CHMP) for further discussion.

It said the new information was from a standard pharmacovigilance review of clinical trial and post-marketing data.

Glaxo’s Tyverb Referred for More Discussion in Europe

GlaxoSmithKline Plc’s Tyverb breast cancer drug was sent back to a European regulatory panel after new data showed the medicine may raise the risk of liver damage, slowing final approval.

The European Commission returned the application to the region’s health-care regulator for further discussion, probably during its April 21-24 meeting, London-based Glaxo said today in an e-mailed statement. An agency committee recommended approval of Tyverb following a review in December.

Tyverb is one of the medicines Glaxo is relying on to help counter slowing growth in sales of its top-selling asthma drug Advair and diabetes pill Avandia and the loss of patent protection on other products. The commission was expected to issue a final decision on the breast cancer drug between Feb. 22 and March 8, Glaxo said.

“It’s not particularly good news,” analyst Nick Turner of Mirabaud Securities in London said in a telephone interview. “This is a drug that promised much but isn’t likely to deliver.”

The new data showed signs that the medicine can raise the level of liver enzymes in patients, a possible warning sign for damage to the organ. Elevated liver enzymes were seen in four out of 1,000 patients, and “generally returned to normal” after they stopped using the drug, according to the U.K. company.

Positive Profile

“GSK believes these data do not change the positive benefit-risk profile for Tyverb in the proposed indication,” Glaxo said in the statement.

Glaxo shares rose 38 pence, or 3.7 percent, to close at 1,054 pence in London trading.

The European Medicines Agency said in December that it recommended conditional approval of Tyverb for breast cancer that has advanced or spread to other parts of the body in patients with the HER-2 gene, which makes the disease more aggressive. Conditional approval is valid for one year while the company obtains more information about the medicine and its effectiveness, EMEA said at the time.

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U.S. health officials have ordered all imports of the blood thinner heparin, and its raw ingredient, stopped at the border for testing to detect a contaminant linked to 19 deaths.

The Food and Drug Administration announced the move Friday, the latest step in its widening investigation of hundreds of allergic-type reactions linked to Baxter International’s heparin injections.

The FDA found the contaminant in 20 of 28 samples of raw heparin that the agency tested from Baxter’s main supplier, a Chinese factory owned by Wisconsin-based Scientific Protein Laboratories.

A different brand of heparin also has been recalled in Germany after 80 patients there got sick, and the German manufacturer said Friday that it was narrowing down the source of contamination to another Chinese supplier.

FDA announced some good news Friday, saying it had learned of no additional deaths and just two more allergic reactions since Baxter recalled the last of the suspect heparin late last month.

Scientists don’t yet know exactly what the contaminant is, except that it mimics heparin so closely that standard drug-purity tests won’t catch it. Nor is it certain that the contaminant is to blame for the allergic reactions, although it is the prime suspect.

But the FDA is “very close” to identifying the substance, a step that should help tell if the contaminant got into heparin by accident or by fraud, said FDA drug chief Dr. Janet Woodcock.

Heparin is derived from pig intestines, and China is the world’s leading supplier. Tiny family-run workshops near slaughterhouses send batches of raw ingredients to larger middlemen before they reach factories like SPL’s in Changzhou. The FDA hasn’t yet inspected those workshops, saying that was something under discussion with Chinese officials.

Two weeks ago, the FDA urged all remaining U.S. heparin manufacturers to start using more sophisticated tests to be sure their products were contaminant-free. Friday, the agency said worldwide testing had begun.

The added hurdle for imports “will improve our safety net,” Woodcock said. “We will get a much better picture of whether there’s any contaminant existing, and we can trace it back” to its source.

Most of the actual import testing will be done by five of the nation’s leading heparin manufacturers, which will be cleared to sell their products once the FDA receives those test results.

The FDA itself will test any remaining shipments that arrive from abroad.

The FDA wouldn’t name the five companies that will do their own testing, and acknowledged it has no plans to do spot checks of the quality of those companies’ tests.

Herapin recalled by Japanese firms

Three Japanese firms recalled the active ingredient in the blood thinner herapin as a “precaution” over concerns of ties to Chinese factories, officials said.

The U.S. Food and Drug Administration announced that three unnamed Japanese firms recalled the active ingredient in herapin manufactured by Scientific Protein Laboratories based in Wisconsin.

At least four people died from allergic reactions to the drug and hundreds suffered life-threatening reactions in the United States and Germany, though none of these reactions stem from products manufactured at Scientific Protein, the Chicago Tribune reported Tuesday.

“The three Japanese companies made clear that the recall was simply a precaution, as there has not been a pattern of adverse reactions to heparin reported in Japan similar to what has been observed in the U.S. and Germany,” Scientific Protein said in a statement Monday.

FDA officials said it found “herapin-like” substances in recalled batches of herapin sold by Baxter International Inc. linked to production facilities in rural China.

The supply chain for herapin production begins in unregulated family-owned pig farms in rural China before reaching Scientific Protein’s Chinese facilities.

Complications of Heparin Therapy

Heparin comes in many forms and is commonly used in cancer patients. Since its discovery in 1923, heparin has been the primary parenteral anticoagulant used worldwide for the prevention and treatment of blood clots and for maintaining patency of catheters. The most frequent side effect of heparin therapy is bleeding. However, a less common but potentially devastating complication of heparin exposure, immune-mediated heparin-induced thrombocytopenia (HIT), is now well described. Paradoxically, immune-mediated HIT is associated with the development of new thrombosis or worsening of preexisting thromboses rather than bleeding.

A mild decline in the platelet count occurs commonly in patients receiving heparin and is most often non-immune mediated. This generally occurs within 5 days after institution of the drug and is not associated with thrombosis. Heparin can be safely continued and the platelet count generally returns to normal within a few days.

Immune-mediated HIT, on the other hand, is characterized by a more significant decline in platelets defined as either a drop in the platelet count to under 150,000 or greater than 50% decline in the platelet count following the initiation of heparin therapy. It typically develops after 4-10 days of heparin therapy but can suddenly occur within 24 hours of heparin exposure if the patient has been sensitized to heparin within the preceding three months. For these reasons, all patients receiving heparin should have their platelet count monitored.

The frequency of HIT may be as high as 3% in patients treated with heparin for at least 4 days. The likelihood that HIT will develop depends upon the source and dose of heparin. Therapeutic doses of heparin are more likely than prophylactic doses to cause HIT and it is most common with unfractionated heparin. In fact, HIT has only rarely been associated with low molecular weight heparin.

HIT is caused by antibodies directed against an antigen complex that is composed of heparin and platelet factor 4. This antibody-antigen complex binds to the surface of platelets resulting in platelet activation and aggregation. It also indirectly leads to the generation of thrombin, further promoting the onset or extension of thrombosis through activation of the coagulation cascade.

In patients who develop HIT, an alarming 50-60% will develop thrombotic complications within 30 days following the diagnosis without further therapy. Venous thromboses are far more likely than arterial thromboses.

Serologic testing should be ordered to confirm the clinical suspicion. However, the results typically are not available for several days, making HIT a clinical diagnosis initially. Indeed, if one waits for the results of the confirmatory tests to act, it may be too late to prevent or effectively treat thrombosis. Laboratory tests include functional assays (serotonin release assay, heparin-induced platelet activation) and an antigenic assay (ELISA). When the functional and antigenic assays are combined both sensitivity and specificity exceeds 90%.

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Drug maker Amgen Inc. said Friday it expanded black box warnings about risks of death and tumor growth of its blockbuster anemia drugs.

The warnings approved by the Food and Drug Administration state that the company’s drugs increased death and accelerated tumor growth in patients with early stage breast cancer and cervical cancer. Earlier labeling warned of similar risks in other types of cancer.

The changes apply to Thousand Oaks, Calif.-based Amgen’s Aranesp and Epogen, as well as Johnson & Johnson’s Procrit. The drugs treat the blood-disorder anemia in patients with kidney failure and those on chemotherapy. Amgen manufacturers all three, though New Brunswick, N.J.-based J & J sells Procrit.

The language states that the problems occurred when doctors treated patients with elevated levels of the drugs, which increase red blood cell levels.

The action came less than a week before a meeting where government advisers are scheduled to review the risks of the blockbuster medications.

Since FDA began scrutinizing the drugs last March, shares of Amgen have sunk 27 percent. U.S. sales of its anemia treatments fell more than 10 percent to $6.3 billion for the year.

Wall Street analysts expect sales to fall further in 2008 following next week’s review by FDA’s cancer experts. The panel could recommend halting use of the drugs for certain types of cancers, or in all cancer patients. Recommendations will not apply to Amgen’s Epogen, which is used almost exclusively by kidney failure patients on dialysis.

If FDA removes only some cancer indications, Amgen’s anemia drug sales could lose between $150 million to $250 million for 2008, according to estimates by Goldman Sachs’ analyst May-Kin Ho.

FDA twice updated anemia drug labels last year, most recently in November. Amgen disclosed new data in December on the drugs’ risks in early stage breast cancer and cervical cancer patients, sending shares downward nearly 20 percent. The new label incorporates detail from those studies.

Bear Stearns analyst Mark Schoenebaum said the effect of Friday’s changes would be minimal for Amgen, since cervical cancer accounts for about 1 percent of the Aranesp market. He also noted that the previous label already highlighted the breast cancer risks.

But Stanford Group Co. analyst Gregory Frykman said the new warnings could attract tougher regulations from Medicare, the government’s health plan for seniors. Last summer Medicare ruled that it would only pay doctors to administer anemia drugs if they were prescribed at low levels.

Frykman said the new warnings could convince Medicare to scale back its policy again, perhaps only paying for the drugs when used in certain types of cancer.

Wall Street reacted positively to the news, sending shares up 1.02 cents, or 2.3 percent, to $45.20 in after-hours trading. Shares fell 14 cents to close at $44.18 in regular trading.

Reference Material on Anemia

Anemia, condition in which the concentration of hemoglobin in the circulating blood is below normal. Such a condition is caused by a deficient number of erythrocytes (red blood cells), an abnormally low level of hemoglobin in the individual cells, or both these conditions simultaneously. Regardless of the cause, all types of anemia cause similar signs and symptoms because of the blood’s reduced capacity to carry oxygen. These symptoms include pallor of the skin and mucous membranes, weakness, dizziness, easy fatigability, and drowsiness. Severe cases show difficulty in breathing, heart abnormalities, and digestive complaints.

One of the most common anemias, iron-deficiency anemia, is caused by insufficient iron, an element essential for the formation of hemoglobin in the erythrocytes. In most adults (except pregnant women) the cause is chronic blood loss rather than insufficient iron in the diet, and, therefore, the treatment includes locating the source of abnormal bleeding in addition to the administration of iron.

Pernicious anemia causes an increased production of erythrocytes that are structurally abnormal and have attenuated life spans. This condition rarely occurs before age 35 and is inherited, being more prevalent among persons of Scandinavian, Irish, and English extraction. It is caused by the inability of the body to absorb vitamin B12 (which is essential for the maturation of erythrocytes).

There are several conditions that cause the destruction of erythrocytes, thereby producing anemia. Allergic-type reactions to bacterial toxins and various chemical agents, among them sulfonamides and benzene, can cause hemolysis, which requires emergency treatment. In addition, there are unusual situations in which the body produces antibodies against its own erythrocytes; the mechanism triggering such reactions remains obscure.

A year ago:

FDA issues new warnings on widely used anemia drugs

Federal health officials have issued stern new warnings for doctors to more carefully prescribe widely used anemia drugs that can increase the risk of death and other serious problems in patients with cancer and kidney disease.

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Spectrum Pharmaceuticals, Inc. today announced that it has received marketing approval from the U.S. Food and Drug Administration (FDA) for Levoleucovorin for Injection. It is indicated after high-dose methotrexate therapy in patients with osteosarcoma, and to diminish the toxicity and counteract the effects of impaired methotrexate elimination or inadvertent overdose of folic acid antagonists. LEVOleucovorin is the only commercially available formulation comprised only of the pharmacologically active enantiomer of leucovorin (Levoleucovorin or (6S)-leucovorin). The Company currently expects its commercial launch by June 2008.

LEVOleucovorin was reviewed under a full NDA, and included an Oncologic Drug Advisory Committee (ODAC) review. Spectrum anticipates that the drug will be listed without any therapeutically equivalent product in the FDA Orange Book. Drugs without therapeutic equivalents are considered ’single source drugs’ which under section 1847A of the Social Security Act generally qualify for a separate reimbursement code with CMS.

“LEVOleucovorin is the first new oncology drug approved by the FDA in 2008, and is the first of what we hope will be many approvals from our pipeline,” said Rajesh C. Shrotriya, M.D., Chairman, President and Chief Executive Officer of Spectrum Pharmaceuticals. “Only four of the 17 drugs approved by the FDA in 2007 were new oncology drugs. This approval is the result of dedicated efforts by our experienced team and serves as a validation of our business model. We are focused on building a diversified portfolio of promising late stage drugs, and advancing them through clinical development, regulatory process and commercialization.”

In preparation for the commercial launch, last year the Company appointed George Uy, an experienced oncology marketing veteran, as its Vice President of Sales and Marketing. George brings more than 20 years of hands on experience, including the launches of ABRAXANE® at Abraxis Bioscience, Inc., and XELODA® at Hoffmann-La Roche Inc. In addition, the Company recently appointed Lynne Murphy as Executive Director of Sales. Ms. Murphy has more than 20 years of sales and marketing experience, which include many sales leadership positions with responsibility for the launch of more than 10 products during her tenure at Bayer Healthcare. Ms. Murphy also led a specialty sales force for Amgen, Inc., and launched Aranesp® Singleject. Ms. Murphy will be responsible for building and assembling a launch team of experienced oncology sales specialists.

“LEVOleucovorin provides physicians and patients with an important treatment alternative to leucovorin,” said Richard A. Bender, M.D., F.A.C.P., Chief Medical Officer of Spectrum Pharmaceuticals. “With this drug, patients undergoing cytotoxic chemotherapy are spared the administration of the pharmacologically inactive dextro-isomer. Preclinical studies have shown that the dextro-isomer may compete with the active levo-isomer for transport into cells.”

The Company plans to file for a supplemental New Drug Application with the FDA for use in colorectal cancer in 5-fluorouracil containing regimens and an NDA amendment for an oral tablet formulation by mid-year 2008.

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AstraZeneca Plc is stopping a clinical trial of Recentin as a treatment for lung cancer after a mid-stage study failed to meet its main goal, although trials in colorectal cancer will move ahead.

The mixed news on Wednesday adds to the company’s patchy record on drug research, analysts said.

Recentin, which is given as a pill, is a rival to Roche Holding AG and Genentech Inc’s blockbuster injectable treatment Avastin. It was being tested against non-small-cell lung cancer, the most common form of the disease.

The Anglo-Swedish drug maker said Recentin had shown some evidence of clinical activity in lung cancer but a Phase II/III trial would not progress into Phase III because among patients given the drug “there appeared to be an imbalance in toxicity.”

John Patterson, the company’s executive director for development, said AstraZenenca remained committed to investigating the potential of Recentin in lung cancer, despite the setback.

AstraZeneca, meanwhile, is progressing with a final stage Phase III clinical trial comparing Recentin plus chemotherapy with Avastin plus chemotherapy in colorectal cancer.

Shares in the drug maker were 0.3 percent lower at 20.01 pounds by 0825 GMT in a broadly unchanged market for drug stocks.

Navid Malik, a pharmaceuticals analyst at Collins Stewart, said lung cancer had potentially been the bigger commercial opportunity for Recentin, given there were already a number of competing drugs in colorectal cancer.

“Recentin was potentially a $1 billion product, so I think this is going to be quite disappointing for AstraZeneca,” he said. “AstraZeneca needs good news from the pipeline.”

AstraZeneca, which is facing the threat of generic competition to its two biggest sellers — Nexium and Seroquel — has suffered a series of setbacks with its new drug pipeline in recent years.

Back in 2001, AstraZeneca was the top-rated stock in the European sector but the failure of five key drugs — Exanta, Iressa, Galida, NXY-059 and AGI-1067 — and the risk from generics has pushed it into the bargain basement, trading at around 8.7 times forecast 2009 earnings.

Recentin, like Avastin, is a targeted cancer therapy — a new class of medicine designed to fight tumours more effectively than chemotherapy, with fewer side effects. It targets three vascular endothelial growth factor receptors used by tumors to get blood supply.

AstraZeneca also has another similar experimental drug in development for lung cancer, called Zactima. Clinical trial results for this product are expected to read out in the coming months.

Astra Drug Moves Ahead in Colon Cancer, Stopped in Lung Test

AstraZeneca Plc’s experimental medicine Recentin will move into late-stage testing for use in colorectal tumors. Trials in lung cancer will be stopped.

The treatment will move into the last of the three stages of testing generally required before regulatory approval in colorectal cancer, London-based AstraZeneca said in a statement today. Tests of the medicine in non-small cell lung cancer will be stopped because of safety concerns that arose in an earlier trial, the company said.

AstraZeneca Announces Recentin(R) As Global Trademark For Novel Cancer Treatment

AstraZeneca today announced RECENTIN™ as the global trademark for AZD2171, its oral, highly potent and selective vascular endothelial growth factor (VEGF) signalling inhibitor. AZD2171 is currently in Phase II/III development for advanced non-small cell lung cancer (NSCLC) and advanced colorectal cancer (CRC) - as well as a wide-ranging signal search programme in other tumours.

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Canadian drug stores have begun stocking a new full-time version of an anti-impotence drug its makers say will allow men to be sexually “spontaneous,” day and night.

Cialis was originally designed to be taken on an “as needed” basis, with one dose lasting 24 to 36 hours, earning it the moniker “Le Weekend” when first approved in Europe in 2002.

Now it’s being repackaged and sold in a once-a-day, lower-dose version. Taken daily, the drug builds in a man’s body until it reaches a circulating level in the bloodstream that would allow a man to be sexually active “whenever the moment is right,” according to a news release issued by drug giant, Eli Lilly.

Dr. Gerald Brock says the once-a-day pill will appeal to men who find timing an issue.

“Taking the drug on a daily basis and having complete spontaneity is going to be a real, genuine advance,” says Brock, a urologist at St. Joseph’s Health Care in London, Ont. Brock has received speakers’ fees and research grants in the past from Eli Lilly.

Once-a-day Cialis will cost $3.80 per capsule, before dispensing fees.

Some critics are uncomfortable with the drug’s expansion and the idea of men taking erectile enhancers in perpetuity, or recreationally. Last year, more than 1.6 million prescriptions for erectile dysfunction drugs were dispensed by Canadian drugstores, according to prescription drug tracking firm IMS Health Canada. About 593,000 of those prescriptions were for tadalafil, the chemical name for Cialis.

“The limited virtue of these erectile dysfunction drugs was that men only needed to take it once in a while, as opposed to statins or osteoporosis drugs or anti-hypertensives,” says Leonore Tiefer, an associate clinical professor of psychiatry at New York University School of Medicine and Albert Einstein College of Medicine in New York.

“On the surface, it seems like it makes life easier, but we know more drugs lead to more complications. In this case, it might be interpersonal complications.

“Is this something that the sexual partner has to give consent to, or even have knowledge of? Unless they’re using it for masturbation, they’re expecting to use it with a partner. If she doesn’t know this, she’s not being given her entitlement to consent.”

Another question is safety. Cialis belongs to a class of drugs known as PDE-5 inhibitors that includes Viagra and Levitra. The pills act on the chemical signals that open up the blood vessels in the penis.

“Is it safe to take a PDE-5 inhibitor every day? It probably is. These drugs are probably much safer than Aspirin,” says Dr. J. Paul Whelan, Braley-Gordon Chair of Urology at McMaster University in Hamilton.

The drugs aren’t thought to benefit men with normal sexual function. And there can be rare side effects, Whelan says, such as severe back muscle spasms.

He says once-a-day erectile dysfunction drugs can help with what is known as “penile rehabilitation” after prostate cancer surgery.

In addition, men who experience side effects with the “on demand” Cialis may better tolerate the once-a-day version, which comes in 2.5 and 5 milligram capsules, says Brock.

“And finally, we as urologists have people who are very sexually active — they may be having sex two or three or more times per week. By taking a very small dose of Cialis every day they can actually take less medication, have greater spontaneity, have lower side effects and, I think, at the end of the day have greater patient and partner satisfaction.”

About 50 per cent of men between the ages 40 and 70 experience erectile problems but only about half of those seek help for erectile dysfunction, or ED, Brock said.

Diabetes, high cholesterol, vascular disease, smoking, stress and relationship issues can increase the risk of erectile problems, Brock said.

Side effects of Cialis include headache, facial flushing and indigestion. The drug should not be used by men who are taking nitrates or those with cardiac disease “for whom sexual activity is not advisable,” Eli Lilly says.

How should I take Cialis?

Take Cialis exactly as it was prescribed for you. Do not take it in larger doses or for longer than recommended by your doctor. Follow the directions on your prescription label.

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