Lipitor Is Going Generic

Lipitor came on the market in 1997, and has raked in some $100 billion for Pfizer even in a crowded market that includes various other cholesterol-lowering statins, many of which have already gone generic.

In the United States, anti-cholesterol drugs account for 255 million prescriptions a year, and about nine million people are taking Lipitor.

India's pharmaceutical giant Ranbaxy won US approval to make the first generic version of Lipitor, known as atorvastatin, from its New Jersey lab, after the company had faced delays from US authorities due to problems with quality control at some of of its Indian factories.

US-based Watson Pharmaceuticals also announced a deal to distribute a generic version made by Pfizer, whereby Pfizer manufactures the drug and Watson sells it, sharing net sales with Pfizer until 2016.

"There should be a price war in that first six months," as more companies elbow for market share of the cheaper generic version of Lipitor, said Morningstar analyst Damien Conover.

Meanwhile, Pfizer is left hunting for new sources of revenue to replace the cash flow from its longtime star, which made up 15 percent of annual sales.

Pfizer has not released its projected losses due to the patent expiration, but its company forecasts call for sales in 2012 of $63-63.5 billion, versus $67.8 billion in 2010.

Lipitor global sales were over $10 billion last year, according to earnings reports. Conover estimated a sales figure of $3.8 billion in 2012.

Pfizer already lost exclusive rights on the product in Canada, Spain, Mexico and Brazil last year, but it continues to earn revenue in developing countries.

In the United States, Pfizer is aiming to defend its territory and undercut its competitors in the generic market.

By forming alliances with pharmacies and health insurance companies, Pfizer will continue to offer Lipitor "at or below generic cost" during the next 180 days, company spokesman MacKay Jimeson told AFP in an email.

"In this 180-day period, typically payers do not receive a significant cost-savings by utilizing a generic," he added.

Lipitor currently costs about $120 per month, a price that should drop 30 percent in December, slightly more than the typical 10-20 percent that a drug price typically falls after a patent expires.

Pfizer has made a deal with Diplomat Specialty Pharmacy in the northern state of Michigan to create the program "Lipitor For You," so customers can sign up online to continue to get the drug in their pharmacy or home-delivered.

It is too early to know if this approach will continue beyond six months. Pfizer could decide to continue to compete with other generic makers but it would have to lower prices even more, which may not prove profitable.

Pfizer is counting on licensing deals that will continue to generate revenue from Lipitor, such as one signed with the French pharmaceutical giant Sanofi-Aventis which will make and market its generic version in France starting in May 2012.

"I don't think they'll be able, in the short term, to compensate, but they have a lot of products in pipeline," said Conover, referring to Pfizer.

Among them are an anti-clotting drug known as Eliquis, and another against rheumatoid arthritis known as tofacitinib, which together could make up a billion dollars in annual sales.

Ratings agency Standard and Poor's said it views the New York-based drug giant as well-placed to survive the expiration of the patent on Lipitor.

"Over the next two years, the company will be able to weather the upcoming storm of patent expirations and associated revenue loss while maintaining its excellent business risk profile and a solidly minimal financial risk profile."

A two-year study released earlier this month showed that maximum doses of Lipitor and its competitor Crestor, made by AstraZeneca, were similarly effective and safe in cutting down plaque in the arteries. Side effects may include liver and muscle problems.

With Lipitor now generic, Crestor will be left as the sole major brand-name statin on the market.

"The market for Crestor will go close to zero," said Cam Patterson, chief of cardiology at the University of North Carolina-Chapel Hill.

(c) 2011 AFP

Coming Soon: Cartilage Replacement!!!!!

Self-assembling sheets of mesenchymal stem cells permeated with tiny beads filled with growth factor formed thicker, stiffer cartilage than previous tissue engineering methods, researchers at Case Western Reserve University have found. A description of the research is published in the Journal of Controlled Release.

"We think that the capacity to drive cartilage formation using the patient's own stem cells and the potential to use this approach without lengthy culture time prior to implantation makes this technology attractive," said Eben Alsberg, associate professor in the departments of Biomedical Engineering and Orthopaedic Surgery, and senior author of the paper.

Alsberg teamed with biomedical engineering graduate students Loran D. Solorio and Phuong N. Dang, undergraduate student Chirag D. Dhami, and Eran L. Vieregge, a student at Case Western Reserve School of Medicine.

The team put transforming growth factor beta-1 in biodegradable gelatinmicrospheres distributed throughout the sheet of stem cells rather than soak the sheet in growth factor.

The process showed a host of advantages, Alsberg said.

The microspheres provide structure, similar to scaffolds, creating space between cells that is maintained after the beads degrade. The spacing results in betterwater retention – a key to resiliency.

The gelatin beads degrade at a controllable rate due to exposure to chemicals released by the cells. As the beads degrade, growth factor is released to cells at the interior and exterior of the sheet, providing more uniform cell differentiation into neocartilage.

The rate of microsphere degradation and, therefore, cell differentiation, can be tailored by the degree to which the microsphere are cross-linked. Within the microspheres, the polymer is connected by a varying number of threads. The more of these connections, or cross-links, the longer it takes for enzymes the cell secretes to enter and break down the material.

The researchers made five kinds of sheets. Those filled with: sparsely cross-linked microspheres containing growth factor, highly cross-linked microspheres containing growth factor, sparsely cross-linked microspheres with no growth factor, highly cross-linked microspheres with no growth factor, and a control with no microspheres. The last three were grown in baths containing growth factor.

After three weeks in a petri dish, all sheets containing microspheres were thicker and more resilient than the control sheet. The sheet with sparsely crosslinked microspheres grew into the thickest and most resilient neocartilage.

The results indicate that the sparsely cross-linked microspheres, which degraded more rapidly by cell-secreted enzymes, provided a continuous supply of growth factor throughout the sheets that enhanced the uniformity, extent, and rate of stem cell differentiation into cartilage cells, or chondrocytes.

The tissue appeared grossly similar to articular cartilage, the tough cartilage found in the knee: rounded cells surrounded by large amounts of a matrix containing glycosaminoglycans. Called GAG for short, the carbohydrate locks water ions in the tissue, which makes the tissue pressure-resistant.

Testing also showed that this sheet had the highest amount of type II collagen – the main protein component of articular cartilage.

Although the sheet was significantly stiffer than control sheets, the mechanics still fell short of native cartilage. Alsberg's team is now working on a variety of ways to optimize the process and make replacement cartilage tough enough for the wear and tear of daily life.

One major advantage of this system is that it may avoid the troubles and expense of growing the cartilage fully in the lab over a long period of time, and instead permit implantation of a cartilage sheet into a patient more rapidly.

Because the sheets containing microspheres are strong enough to be handled early during culturing, the researchers believe sheets just a week or two old could be used clinically. The mechanical environment within the body could further enhance cartilage formation and increase strength and resiliency of the tissue, completing maturation.

Provided by Case Western Reserve University (news : web)

Baby Boomers Feed The Need For Joint Replacements

US baby boomers are fueling a wave of joint replacement surgeries, hoping to use new artificial knees and hips to stay active as they get older.

With 76 million baby boomers still kicking, many are rejecting the sedentary lifestyle of their parents' generation, and are using advances in technology and surgical techniques to keep on running, cycling, skiing and engaging in other sports.

The 45-64 age group accounted for more than 40 percent of the more than 906,000 total knee or total hip replacement surgeries in 2009, the last year for which figures were available from the American Academy of Orthopedic Surgeons.

Boomers will account for a majority of these joint replacements in 2011, according to projections by Drexel University specialist Steven Kurtz.

The study projects the 45-64 age group will account for a 17-fold increase in knee replacements alone to 994,000 by 2030. Active boomers often accelerate the arthritis which wears down their joints, and obesity is another factor.

"We are still doing patients 65 years and up, but the volume is increasing dramatically among 45-64 year-old patients," said Douglas Dennis, a Colorado orthopedist who has performed some 5,000 knee replacements and 4,000 hip replacements over his career.

Decades earlier, most replacements were in elderly patients unable to walk. But Dennis said, "We are now performing them in younger age patients. We have made great strides in our ability to revise them should they fail."

A number of his patients are avid skiers who have had several attempts to repairknee injuries, but want to keep active.

"We encourage the patients to be active," he said. "But I don't favor things like racquet sports, soccer or basketball" which can put extra strain on joints.

Some patients are drawing hope from new technology, such as a so-called 30-year knee from British-based Smith & Nephew, endorsed by former tennis star Billie Jean King.

"I feel like I'm 20 again, and I'm back on the courts playing tennis," King says in her endorsement after double knee replacement surgery. But some physicians say people these claims may not be realistic.

"That knee has been designed in the last five years, so how can you say it is going to last 30 years?" says Dennis.

"It is disingenuous marketing... It is harmful rather than helpful. If I had 20 years of data on young patients playing racquet sports, and it showed good survivorship, I would change my opinion. But we don't have that data."

Still, some boomers persist.

Dick Beardsley, an avid distance runner who came within two seconds of winning the Boston Marathon in 1982, said he is determined to show he can come back from two knee replacements.

"I've been a runner all my life," Beardsely told AFP from his home in Austin, Texas, a year after he had replacement surgery for his left knee.

"For a while I thought I might become a cyclist. But I had to give this a try."

Beardsley, 55, is back to running 70-80 miles a week to prepare for the April marathon in Boston, without any problem for his left knee replaced in 2010 or his right knee replaced three years ago.

"The first six to eight weeks (after surgery) are brutal," he said.

"But I would keep at it, run a mile... eventually I got back to running the same pace I was before the knee surgery."

Beardsley, who works as a motivational speaker and operates running camps for adults, said he knows he is flying in the face of medical advice.

When he told his doctor about his training, "He told me, 'I'm not going to tell you to keep running, but I'm not going to tell you to stop.'"

His exams have shown no excess wear on the joints, and believes this is in part due to his small frame and a technique he uses -- "midfoot, forefoot" without striking his heels.

Allen Beale, a 62-year-old computer consultant in Durham, North Carolina, said he is extremely satisfied with the hip replacement he received two years ago, when he was barely able to walk.

Now, he is back at golf, motorcycling and other activities.

Before the surgery, he said, "it had gotten to the point where I couldn't stand up and move... Now it feels so good I don't even know it's there."

Among celebrities getting surgery are former Olympic gymnast Mary Lou Retton (hip), singer Billy Joel (double hip) and actress and workout guru Jane Fonda (knee).

Even if the new joints work as promised, it remains unclear whether supply will be able to keep up with demand, and if the costs will become overwhelming.

A study appearing the journal Health Affairs suggests the costs may reach $50 billion for the government Medicare program alone by 2030 if current trends continue.

And with government reimbursement reduced, and private insurance following suit, the incentives for doctors are declining.

A separate study co-authored by Thomas Fehring showed that if current trends continue, by 2016, 46 percent of needed hip replacements and 72 percent of needed knee replacements will not be able to be completed.

"I was somewhat shocked at the shortfall that we predicted," said Fehring, an orthopedic surgeon in Charlotte, North Carolina.

"The number of people getting joint replacements is going up, the number of young surgeons is going down," said Dennis.

"There are fewer people going into this specialty."

If boomers can't wait, technology may come up with alternatives which may avert the need for radical surgery.

Kurtz notes in his study that he did not account for the "potential for future alternative technologies, such as cartilage regeneration or tissue engineering, or drug therapies that limit progression of joint diseases, which may preempt the need" for joint replacement.

(c) 2011 AFP

Little Evidence of Heart Risks From ADHD Meds

TUESDAY Nov. 1, 2011 -- Medications commonly used to treat attention-deficit/hyperactivity disorder don't appear to raise the risk of heart attacks and other cardiovascular problems in children and young adults, new research shows.

And if any increased risk from stimulants such as Ritalin, Adderall and Concerta does exist, the danger in absolute numbers would be extremely low, said Dr. William O. Cooper, lead author of a study published online Nov. 1 in the New England Journal of Medicine.

"This is the largest study to date, and I feel this provides reassuring information about risk," said Cooper, a professor of pediatrics and preventive medicine at Vanderbilt University in Nashville, Tenn.

Almost 3 million children in the United States take prescription medications for attention-deficit/hyperactivity disorder (ADHD) each year. Children with the neurobehavioral disorder have excessive levels of activity, inattention and impulsiveness.

For the typical child diagnosed with the disorder, "if ADHD medications appear to be an important part of a treatment regimen, the worry about these cardiac risks should certainly be less," Cooper continued. "Having said that, it's really important that each child be evaluated by his or her health care provider to decide if it makes sense."

Several years ago, a few reports of sudden death, heart attacks and stroke among users raised concern among parents and health care providers about the safety of these medications, which are prescribed to help children focus and manage their behavior.

Canadian health authorities briefly removed Adderall from the market in 2005, and the U.S. Food and Drug Administration (FDA) required that ADHD drugs carry a "black box" label warning and a patient guide.

Subsequently, the American Heart Association stated it would be "reasonable" to give kids screening electrocardiograms before starting them on stimulant medication.

"This really added to the concern and confusion among families and health care providers," Cooper said.

To try to settle the question, Cooper and his colleagues analyzed data on 1.2 million children and young adults aged 2 to 24 enrolled in four large health plans around the United States. This was called a meta-analysis.

"We compared those currently using ADHD medicines to those not using these medications to look at their risk for sudden death, heart attack and stroke," Cooper explained. The medications included methylphenidate (Ritalin, Concerta), dexmethylphenidate (Focalin), dextroamphetamine(Dexedrine), amphetamine salts (Adderall), atomoxetine (Strattera) and pemoline (Cylert).

The authors concluded that there was really no raised risk of heart problems with these medications, although they also acknowledged the possibility of up to an 85 percent increased risk.

That's because the large size of the study and the rarity of events made it difficult to track the relative increased risk.

"Placing that in context, even if there was a doubling, the absolute risk would be very, very low," Cooper said.

The findings are similar to several reports published after the FDA's safety review was compiled, the authors said.

Some children may have underlying heart disease or other problems that could potentially place them at risk, Cooper added. "We would need to think about their individual risk," he said, "but on a population level, this suggests there is no increased risk."

Dr. Howard S. Weintraub, clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Medical Center in New York City, agreed that the data should allay fears about the drugs' safety.

The findings indicate that "when these medicines are appropriately utilized and kids are screened appropriately, there is no increased risk," Weintraub said.

"This is a large trial that scrutinizes the lives of a lot of young kids," he said. "The only issues are that the population was from a Medicaid basis so it may be a little different from how some other people are treated but, if anything, you would expect them to be at greater risk."

Although there's no longer a universal mandate for EKG screening in children considering stimulant drugs for ADHD, they "should still be screened for risk factors such as family history of sudden unexplained cardiac death, a child history of unexplained seizures or congenital heart disease," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at the Steven and Alexandra Cohen Children's Medical Center of New York in New Hyde Park.

He added that the results of the new study "hopefully provide further reassurance to parents and professionals that stimulant medications don't pose a significant cardiovascular risk."

More information

The U.S. National Institute of Mental Health has more on ADHD.

New Multiple Sclerosis Therapy Promising in Early Trial

TUESDAY Nov. 1, 2011 -- Multiple sclerosis patients may eventually benefit from a novel treatment that takes aim at the abnormal behavior of a specific type of immune cell, preliminary research suggests.

The errant behavior of the cells in question -- known as "B cells" -- is viewed as key to the development of this chronic and disabling nervous system disease, commonly called MS.

The new therapy's potential is only in the early stages of exploration, cautions an international study team comprised of researchers from the United States, Canada, Switzerland and the Netherlands, in the report published in the Nov. 1 online edition of The Lancet.

But initial indications suggest that the new antibody drug, called ocrelizumab, successfully targets these renegade cells with hopeful results: a significant reduction in disease-related inflammatory brain lesions.

"Our findings show that ocrelizumab rapidly suppresses inflammatory activity," noted the study authors, led by Dr. Ludwig Kappos from the University Hospital, Basel, Switzerland, in a journal news release.

Describing the targeting of B cells as an "innovative therapeutic approach," Kappos and his colleagues reported that in testing among 218 patients, the drug's impact on lesions was "rapid and pronounced." What's more, to date the treatment appears to be safe.

The study authors noted that MS is a progressively debilitating disease that attacks an individual's central nervous system, disrupting the normal brain, spinal cord and optic nerve function.

A classic characteristic of the disease is inflammation, which takes the form of brain lesions.

The immune system's T cells have long been implicated in disease progression, but the notion that B cells may also play a major role is relatively new.

With this new potential target in mind, researchers configured ocrelizumab to specifically focus on a protein (CD20) found on the surface of certain B cells.

To test the drug, Kappos and his team recruited patients aged 18 to 55 seeking MS treatment in 79 centers in 20 countries.

The patients were divided into four groups, treated with: a low dose of ocrelizumab (600 milligrams); a high dose of ocrelizumab (2,000 mg); a well-known MS inflammation treatment known as "intramuscular interferon beta-1a"; or a sugar pill (placebo). After 24 weeks, some of the doses were adjusted.

The result: at week 24, all of the patients receiving either dose of ocrelizumab fared better in terms of lesion count than either the placebo or standard treatment groups.

The number of active lesions had dropped 89 percent more among the 600-mg group compared with those getting a placebo. Similarly, those in the 2,000-mg group experienced a 96 percent bigger drop in lesions. What's more, relapse rates were much lower among those taking the new drug, in contrast to those taking a placebo.

The investigators further noted that even eight months after treatment launch, no serious adverse effects were directly attributable to the new drug.

That said, Dr. Moses Rodriguez, a professor of neurology and immunology at the Mayo Clinic in Rochester, Minn., disputed the premise that ocrelizumab is shaping up as anything new and innovative.

"In fact, there's nothing novel about this at all," he said. "There is another drug, called rituximab, that's been in early trials for MS for years. And all this new drug is attempting to do is replicate the same that rituximab already does. And I see no major advantage of this drug versus that older drug. It's not better or worse. It's the same," Rodriguez noted.

"So bottom-line, I would not sell this as a major breakthrough in MS," cautioned Rodriguez. "It's not."

Funding for the study was provided by F. Hoffmann-La Roche and Biogen Idec. Inc.

More information

For more on multiple sclerosis, visit the U.S. National Library of Medicine.