Traffic jam in brain causes schizophrenia symptoms

http://www.physorg.com/news169150751.html

August 10th, 2009

There are fewer pathways (green strands) for information to flow between neurons in the brain of a mouse bred to exhibit symptoms of schizophrenia compared to a normal mouse. Fewer pathways make it hard for information to flow between neurons and results in the symptoms of schizophrenia Credit: Peter Penzes, Northwestern University Feinberg School of Medicine

Schizophrenia waits silently until a seemingly normal child becomes a teenager or young adult. Then it swoops down and derails a young life.

Scientists have not understood what causes the severe mental disorder, which affects up to 1 percent of the population and results in hallucinations, memory loss and social withdrawal.

But new research from the Northwestern University Feinberg School of Medicine has revealed how schizophrenia works in the brain and provided a fresh opportunity for treatment. In a new, genetically engineered mouse model, scientists have discovered the disease symptoms are triggered by a low level of a brain protein necessary for neurons to talk to one another.

A Traffic Jam in Brain

In human and mouse brains, kalirin is the brain protein needed to build the dense network of highways, called dendritic spines, which allow information to flow from one neuron to another. Northwestern scientists have found that without adequate kalirin, the frontal cortex of the brain of a person with schizophrenia only has a few narrow roads. The information from neurons gets jammed up like rush hour traffic on an interstate highway squeezed to a single lane.

"Without enough pathways, the information takes much longer to travel between neurons and much of it will never arrive," said Peter Penzes, assistant professor of physiology at the Feinberg School. He is senior author of a paper reporting the findings published in a recent issue of the Proceedings of the National Academy of Science. Michael Cahill, a Feinberg doctoral student in neuroscience, is the lead author.

First Mouse Model to Develop Disease as a Teenager

Penzes discovered the kalirin effect after he created the mouse model, which was the first to have a low level of kalirin and the first to develop symptoms of schizophrenia as an adolescent (two months old in mouse time). This mimics the delayed onset of the disease in humans. In normal development, the brain ramps up the production of kalirin as it begins to mature in adolescence.

New Direction for Treatment

"This discovery opens a new direction for treating the devastating cognitive symptoms of schizophrenia," Penzes said. "There is currently no treatment for that. It suggests that if you can stimulate and amplify the activity of the protein kalirin that remains in the brain, perhaps we can help the symptoms."

Currently the only drug treatment for schizophrenia is an antipsychotic. "The drugs address the hallucinations and calm down the patient, but they don't improve their working memory (the ability of the brain to temporarily store and manage information required for complex mental tasks such as learning and reasoning) or their ability to think or their social behavior," Penzes said. "So you end up with patients who still can't integrate into society. Many attempt suicide."

Similarities Between Human and Mouse Brains

A few years ago in postmortem examinations of schizophrenic human brains, other scientists had found fewer connections between the brain cells in the frontal cortex and lower levels of kalirin. But the scientists couldn't show whether one condition led to the other.

With the new mouse model, Penzes was able to demonstrate that the low level of kalirin resulted in fewer dendritic spines in the frontal cortex of the brain, the part of the brain responsible for problem solving, planning and reasoning. Other areas of the brain had a normal number of the dendritic spines. Human brains and mouse brains share many similarities in the way they function, Penzes said.

The new schizophrenic mouse model also exhibits more schizophrenic symptoms than other models, making these mice especially good for drug testing and development, Penzes said. The mice with low amounts of kalirin had a poor working memory, were antisocial and hyperactive.

Penzes said future studies would aim at enhancing the function of kalirin in the brain in an effort to correct the cognitive symptoms of schizophrenia.

Source: Northwestern University (news : web)

I won't be surprised if they do change their mind.

Nexavar is worth considering. BP will need to be monitored closely especially since the patient got Avastin before.

Astellas might want to leave due to this extra trial and cost.

And carrots still don't mind the vesivirus and the risk of viral contamination for ProCellEx is still very low but you still haven't figured out why :)

Genzyme scraps drug material at tainted plant

http://www.reuters.com/article/marketsNews/idINN1046442820090810?rpc=44

* Lowers previously reported Q2 earnings

* Sees 2009 results at low range of forecast

* Shares up 4.5 percent

(Adds analyst comment in paragraphs 4, 5; updates shares)

By Lewis Krauskopf

NEW YORK, Aug 10 (Reuters) - Genzyme Corp (GENZ.O: Quote, Profile, Research, Stock Buzz) said on Monday it will scrap most unfinished batches of its top-selling drug after the plant where they were being produced was contaminated by a virus, and that 2009 results will come in at the low end of its forecasts.

Genzyme previously warned of a gloomy forecast because of unusable material, and its beaten-down shares rose 4.5 percent to $50.36 after the announcement.

The biotechnology company's disclosures stem from the shutdown of a key manufacturing plant in Boston due to the contamination, which it said in June it had detected. Hurt by the plant woes, the stock is off some 25 percent this year.

Robert W. Baird analyst Chris Raymond called the latest plant update a "mixed bag."

"While this presents downside to our numbers, we think many investors expected as much," Raymond said in a research note.

Genzyme said its decision to discard about 80 percent of the unfinished batches of its Cerezyme drug for Gaucher disease resulted in a new write-off of about $8.4 million. It said this reduced its second-quarter results, first reported on July 22.

Genzyme revised downward its second-quarter net income to $187.6 million, or 68 cents per share, from $192.2 million, or 70 cents per share. Earnings excluding one-time items were revised downward to $226.6 million, or 82 cents per share, from $232.5 million, or 85 cents per share.

Genzyme said it now expects 2009 earnings, revenue and Cerezyme sales to come in at the low end of the forecasts it provided on July 22.

Genzyme had halted production of Cerezyme, as well as another big seller, Fabrazyme for Fabry disease, after detecting a virus at the plant that did not endanger health, but interfered with cell growth.

Manufacturing at the Allston plant has resumed, and Genzyme expects to begin releasing new material in November and December, the company said.

"Reaching a decision on the work-in-process material has been difficult for us as we balance the medical benefit of Cerezyme for patients with minimizing the risk to our newly cleaned Allston plant," Chief Executive Henri Termeer said in a statement.

"Now that we have resumed production, we are focused on the road to recovery."

Genzyme previously said it was evaluating the unfinished Cerezyme material and, if the material proved unusable, full-year results would be at the low end of forecasts.

On Monday, the company said it is still evaluating what to do with the remaining unfinished Cerezyme batches.

"The problem is it still could be a little worse because they could write off the remaining 20 percent," said Jon Stephenson, an analyst with Summer Street Research.

Last month, Genzyme said the U.S. Food and Drug Administration would reinspect the plant, sending shares lower.

"I just can't see how the stock is going to significantly outperform from the current levels because there's still a tremendous amount of uncertainty out there," Stephenson said.

Catch ya's later moderator

Just step aside, Fred, and let them fight



Photo in the News: Python Bursts After Eating Gator

http://news.nationalgeographic.com/news/2005/10/1006_051006_pythoneatsgator.html

Goldman adds Genzyme to sell list

http://www.reuters.com/article/rbssHealthcareNews/idUSBNG39584120090807

Aug 7 (Reuters) - Goldman Sachs added Genzyme Corp (GENZ.O: Quote, Profile, Research, Stock Buzz) to its Americas conviction sell list, and said manufacturing setbacks at one of its plants may impair long-term growth at the company and near-term shortage of its drug Cerezyme may be more severe than expected.

In June, the biotechnology company halted production of two of its top-selling drugs, Cerezyme and Fabrazyme, after detecting a virus at a Boston plant that U.S. regulators had already cited for deficiencies.

By the end of July, the U.S. Food and Drug Administration notified Genzyme that it will re-inspect the plant because the company did not take sufficient action to correct equipment maintenance and process control problems.

Cerezyme, which was being manufactured in the plant, is approved for Gaucher disease -- a rare disorder in which patients are deficient in an enzyme that breaks down a type of fat molecule.

Genzyme may not be able to meet the demand for Cerezyme in 2009 and the shortage might have long lasting negative impact due to persistent dose reduction and possible share erosion to competitors such as Shire, Goldman Sachs said and reduced its price target on the stock by $8 to $44.

Earlier this month, rival Shire Plc (SHP.L: Quote, Profile, Research, Stock Buzz) reported positive trial results of its Gaucher drug.

The risk of single source manufacturing until at least 2011 could pressure multiples, the brokerage added.

US review of Amgen bone drug to focus on safety

http://www.reuters.com/article/marketsNews/idINN0941931120090809?rpc=44

* Infection risk at forefront

* Panel expected to recommend approval

By Deena Beasley

LOS ANGELES, Aug 9 (Reuters) - Thursday's U.S. Food and Drug Administration advisory panel review of denosumab, Amgen Inc's (AMGN.O: Quote, Profile, Research, Stock Buzz) experimental osteoporosis drug, will likely center on safety, particularly the risk of serious infections.

Denosumab -- to be sold under the brand name Prolia -- is seen as Amgen's best hope of jump-starting growth now that safety concerns have deflated sales of its flagship anemia drugs.

The biotech company filed in December for approval of denosumab as a treatment for post-menopausal osteoporosis and for treating and preventing bone loss in patients undergoing hormone ablation for either prostate or breast cancer.

Given denosumab's easy administration and infrequent dosing, "a lot (of osteoporosis patients) will end up being treated with this drug right off the bat," said Dr.John Adams, an endocrinologist at the University of California, Los Angeles who was not involved in denosumab's development.

"We do think that ultimately it (denosumab) is going to get approved," said Cowen & Co analyst Craig Gordon. "I think what's unclear is the extent of post-marketing commitments Amgen will be required to do."

BRIEFING DOCUMENTS ON TUESDAY

Investors will get a sense of the FDA's thinking on Tuesday, when the agency is expected to release internal memos with a preliminary analysis of Amgen's denosumab data.

FDA reviewers will present the views to the advisory panel on Thursday before the outside experts make recommendations on the drug. The agency usually follows committee advice when making final approval decisions.

Denosumab is also being developed for treating bone loss in cancer patients.

BMO Capital Markets analyst Jason Zhang estimated combined sales of denosumab in the osteoporosis and oncology markets of $2.4 billion by 2012.

Trials of the drug in post-menopausal women with osteoporosis found that it reduced the risk of spine fractures by nearly 70 percent, but some studies showed a higher rate of serious skin infections that required hospitalization.

Amgen is banking on the impressive clinical data, along with a patient-friendly dosing schedule of twice-yearly injections to help it compete with existing osteoporosis drugs, some of which are already available as low-cost generics.

RISK MANAGEMENT PLAN?

Denosumab is a bioengineered antibody that targets RANK ligand, a protein involved with bone-destroying cells called osteoclasts.

In addition to infection risk, the FDA committee is also likely to discuss the risk of cataracts, since an imbalance of incidence was seen in one trial, and the risk of a rebound in bone turnover markers, said Gordon at Cowen & Co.

"We expect the FDA to basically concede efficacy and mostly just address safety," he said.

The FDA may approve the drug with a required risk management plan to minimize side effects, an increasingly common scenario for new medicines. The agency can mandate post-approval studies, distribution limits or other measures.

Bad news for the stock would include a recommendation for a stringent risk management plan, which could limit the likelihood that a doctor would prescribe the drug.

In the best case, the panel would simply call for active surveillance of side effects, Gordon said.

Dr. Adams said the risk of infection with denosumab could be mitigated by ensuring that patients are getting sufficient vitamin D before they are started on the drug.

"RANK ligand is made by the body's lymphocytes -- part of the immune system," he said. "When you give this drug (denosumab) to someone who is vitamin D deficient, they are doubly immuno-compromised."

In the cancer setting, where a much higher dose of the drug is used, questions have been raised about the risk of osteonecrosis -- or deterioration -- of the jaw, a serious side effect associated with some other osteoporosis drugs.

The FDA is slated to issue a decision on the denosumab marketing application by Oct. 19, but many on Wall Street expect that the deadline could be missed given the agency's recent track record of delayed decisions.

BMS-650032 will be presented Tue, Nov 03:

"Safety, Tolerability, Pharmacokinetics and Antiviral Activity
following Single- and Multiple-Dose Administration of BMS-
650032, a Novel HCV NS3 Inhibitor, in Subjects with Chronic
Genotype 1 HCV Infection."

ABT has 2 non-nuc polymerase (ABT-333, ABT-072) and Enanta's protease inhibitor (ABT-450).

This SGP's presentation is news:

"High Sustained Virologic Response (SVR) in Genotype 1 (G1) Null Responders to Peg-Interfeon alfa-2b (P) plus Ribavirin (R) When Treated with Boceprevir (Boc) Combination Therapy."

Pharma facts

http://www.latimes.com/news/opinion/commentary/la-oe-critser9-2009aug09,0,3191932.story?page=1

A quiz on how the drug companies interact with the healthcare industry.

By Greg Critser, August 9, 2009

With the pharmaceutical companies at the bargaining table on healthcare reform, and Congress considering new restrictions on drug advertising, it may pay to bone up on some facts about the industry with the following quiz:

1. What percentage of Americans over the age of 65 take at least one prescription drug on a daily basis?



a. 20%

b. 40%

c. 60%

d. 75%





2. In 2005, what percentage of all continuing medical education for physicians was paid for by Pharma?



a. About 25%

b. About 50%

c. About 75%

d. About 90%





3. Who told a congressional panel in 1983 that "we believe direct advertising to the consumer introduces a very real possibility of causing harm to patients who may respond to advertisements by pressuring physicians to prescribe medications that may not be required."



a. The chairman of the Federal Trade Commission

b. The chairman of Abbott Laboratories

c. The head of the Food and Drug Administration

d. The head of the Consumers Union





4. In the same hearings, who said, "The potential pressures of public advertising of prescription drugs on the scientific decisions of the physician are both unwise and inappropriate."



a. The chief of the FDA

b. The chief of Eli Lilly & Co.

c. The chief of the Sioux Nation

d. The chief of the House Committee on Science and Commerce





5. Who, in 1983, first proposed that the FDA roll back its regulation and allow drugs to be advertised?



a. The chairman of the FTC

b. The chairman of Abbott Lab- oratories

c. The head of the FDA

d. The head of the Consumers Union





6. In 2003, what did the head of Pfizer pharmaceuticals say was the key to the industry's future success?



a. That "we should push as hard as we can to get patients to talk to their doctors about our newest drugs."

b. That "we should give patients good, solid facts and encourage them to use logic to make their decisions."

c. That Pharma "must move toward the emotional way of marketing, because in that way we can move toward the spiritual-ethical method."

d. That Pharma should "really think about free Krispy Kreme coupons as a way of encouraging sales."





7. Today, most new prescription drugs are expected to show profitability within:



a. 90 days

b. 120 days

c. one year

d. three years





8. According to the leading scholar on the subject of attention deficit and hyperactivity disorder (ADHD), Ritalin, a stimulant, became the leading treatment for ADHD because:



a. It was effective

b. It was safe

c. It was not called amphetamine

d. It made teachers happy





9. In 2002, who said "we are entering what could be the golden age for kids and pharmaceuticals"?



a. The head of PhRMA, the powerful pharmaceutical lobby

b. The head of Eli Lilly

c. The head of Pfizer

d. The head of the drug committee for the American Academy of Pediatrics





10. In ancient Greece, "pharmakon" meant:



a. An untrustworthy agricultural worker

b. A reformed criminal

c. A delicious beverage

d. Both "remedy" and "poison"



Answers: 1-d; 2-d; 3-b; 4-b; 5-c; 6-c; 7-a; 8-c; 9-d; 10-d



Greg Critser is the author of "Fat Land," "Generation Rx" and the forthcoming "Eternity Soup: Inside the Quest to End Aging."

It is certainly going to be a breakthrough but still a long way to success. Mimicking Golgi or any other organelle is highly challenging.

Oops, I see the problem with the links. You need to go to the Liver Meeting page and look for abs/presentations and then to the Itinerary Planner and Browse by date.

VRTX - Study C208 data of telaprevir administered BID or TID will be presented at AASLD (No. 194 on this page):

http://aasld2009.abstractcentral.com/planner

AASLD abstracts' titles are out. No. 62 on this page is interesting:

http://aasld2009.abstractcentral.com/planner

Brainsway rises on positive trial results

http://www.globes.co.il/serveen/globes/docview.asp?did=1000487726&fid=942

Deep transcranial magnetic stimulation is safe and effective for treating depression.

Adi Ben-Israel6 Aug 09 14:14

Brainsway Ltd. (TASE:BRIN) today announced success in the clinical trial of its Deep TMS (transcranial magnetic stimulation) for the treatment of depression.

56 patients participated in the trial, which was conducted at Hadassah Medical Organization in Jerusalem and Beer Yaakov Mental Health Center. The final results of the safety and effectiveness study found that of the 22 of the 45 patients who completed at least ten treatments showed statistically significant improvement and 13 patients achieved full recovery.

One patient had a brief epileptic episode during treatment, while some patients reported slight headaches, mostly during the first treatments.

Brainsway said that the results mean that Deep TMS is a safe and effective treatment for depression.

Brainsway is simultaneously conducting a number of trials of Deep TMS on a number of neurological disorders. Earlier this week, the Veterans Administration Medical Center of Los Angeles announced that it will try to treat attention deficit disorder (ADD) with Deep TMS. In June, the Ministry of Health approved a trial of the system to helping chronic lung disease patients quit smoking. In April, the US National Institute on Drug Abuse (NIDA) announced that it conduct an effectiveness of Deep TMS for the treatment of cocaine addiction. In February, the Veterans Administration Pittsburgh Medical Center announced a trial of the system for the treatment of obesity. Charite University Hospital in Berlin will test the device for the treatment of multiple sclerosis. In June, the Ministry of Health approved a trial of the system to helping chronic lung disease patients quit smoking

BIIB ELN - Elan sues as Biogen seeks control over Tysabri

http://www.reuters.com/article/marketsNews/idUSN0631736820090806?rpc=401&

They may be doing good science, but whether their claims will be realized is another question. Without reading their manuscripts, my gut feeling is that there is no magic drug that can kill all viruses. Maybe some cross reaction with similar viruses. If someone has the time and will, there are some publications in Functional Genetics' site:

http://www.functional-genetics.com/

Novo Nordisk expects Victoza (liraglutide) to be approved by the FDA in a few months' time.

http://www.reuters.com/article/rbssHealthcareNews/idUSDKT00454620090806

GIVN - good quarter, will get better with Fuji in Japan

Given Imaging posts higher Q2, backs '09 view

http://www.reuters.com/article/marketsNews/idINBNG35056620090805?rpc=44

* Q2 EPS 12 cents vs est 6 cents

* Q2 revenue $36 mln vs est $34.6 mln

* Backs '09 profit and revenue view

Aug 5 (Reuters) - Given Imaging Ltd (GIVN.O: Quote, Profile, Research, Stock Buzz) posted a 69 percent jump in quarterly net profit that also topped market estimates, helped by strong sales of its Bravo pH monitoring system and PillCam video capsules, and backed its 2009 outlook.

Net income for the second quarter was $4.9 million, or 16 cents a share, compared with $2.9 million, or 9 cents a share, in the year-ago quarter. [ID:nWNBB9912]

Excluding a tax benefit, the company earned 12 cents a share, according to Reuters Estimates.

Worldwide revenue rose 9 percent to $36.0 million. PillCam SB sales rose 8 percent.

For 2009, the company still expects earnings of 46 cents to 54 cents a share, excluding items, on revenue of $141 million to $148 million.

And we know how you guys enjoy your time:

Men spend a year staring at women

http://www.telegraph.co.uk/news/newstopics/howaboutthat/5970007/Men-spend-a-year-staring-at-women.html

MEN spend almost a year of their lives ogling women, a survey claimed. The average man will spend almost 43 minutes a day staring at 10 different women.
That adds up to 259 hours - almost 11 days - each year, making a total 11 months and 11 days between the ages of 18 and 50. But researchers found that the males of the species are not the only ones admiring the opposite sex as women sneak a peek at six men for just over 20 minutes a day, on average.
That adds up to almost six months spent admiring men from afar between the ages of 18 and 50.
Mark Ireland, spokesman for Kodak Lens Vision Centres, which carried out the poll, said: “Men are renowned for looking at women but it’s interesting to find out exactly how long they spend eyeing girls up. “A year of their life is a long time to spend with their eyes fixed on the opposite sex. “However, men have their work cut out if they are going to impress a woman as they spend half the amount of time gazing at guys.”
The poll of 3,000 people revealed the supermarket as the location for the most ogling, followed by a pub and nightclub. Women rely on the traditional “ogling hotspots” with pubs or bars their most popular locations. But whilst the majority of men and women feel flattered at being gazed at, guys are more likely to enjoy it with 19 per cent saying it makes them feel happy, compared to just nine per cent of women. Instead, 16 per cent of girls are just left feeling uncomfortable, while 20 per cent say it embarrasses them. Over 40pc of women stated eyes as first attraction whilst the same amount of men admitted their eyes were immediately drawn to a women’s body. But more than half of Brits have also been left red-faced after being caught looking at someone.
A third have ended up arguing with their partner over their roving eye, with one in 10 have even split up with a partner because of it.
The staring has worked for some with 35 per cent of Brits saying they started a relationship with someone they eyed-up.
The study also found that more than a third of Brits would miss being able to admire the opposite sex if they couldn’t see, whilst another 71 per cent would miss their partner’s face. And 61 per cent of people are worried about their eyesight fading.
Despite this, two thirds admit they don’t prioritise the health of their eyes, and 38 per cent haven’t had their eyes tested for over two years.
Top five spots men look at women: supermarket, pub/bar, nightclub, work, shops. Top five places women look at men: pub/bar, shops, on public transport, supermarket, work.

Generic drug superstars

http://money.cnn.com/2009/08/05/news/companies/top_generic_drugs.fortune/index.htm?source=yahoo_quote

...Here, based on data from IMS, are the best-selling generic drugs of last year:

1. Fentanyl

Launched: January 2005
2008 sales: $900 million
Branded equivalent: Duragesic, by Janssen, 2008 sales of $1.1 billion

Mylan's copy of Janssen's Duragesic patch was the top-selling generic drug last year, raking in about $500 million for the Canonsberg, Pa.-based company. The patch treats pain related to cancer by delivering a steady release of fentanyl, a super-strong painkiller, to the nervous system over a 72-hour period. Though several other generics makers -- including Watson Pharmaceuticals (WPI), Lavipharm S.A., Actavis Group, and Teva Pharmaceutical Industries (TEVA) -- produce similar products, Mylan (MYL, Fortune 500) secured the first legal approval in November 2003 and represents just over half of the $900 million market for fentanyl-based drugs.

2. Amlodipine besylate and benazepril hydrochloride

Launched: July 2007
2008 sales: $779 million
Branded equivalent: Norvasc, by Pfizer (PFE, Fortune 500), 2008 sales of $2.2 billion

Pfizer's Norvasc, which treats high blood pressure and chronic chest pain, had annual sales of $2.4 billion in 2008. But its generic counterpart, amlodipine, is gaining quickly, with revenues of $779 million last year. The biggest producer and distributor of amlodipine is Israel-based Teva, whose approval to produce it was approved by the FDA in May 2007. Teva set a generic industry record with $2.38 billion in sales in the second quarter of 2007, thanks in large part to the successful launch of amlodipine.

3. Metoprolol succinate

Launched: May 2008
2008 sales: $675 million
Branded equivalent: Toprol, by AstraZeneca (AZN), 2008 sales $807 million

The generic equivalent of AstraZeneca's Toprol, made by St. Louis-based K-V Pharmaceutical Company (KVA), treats high blood pressure. K-V first started making the drug six years ago, but it took five years to settle patent-infringement lawsuits with AstraZeneca. The generic version hit the market in May 2008. Since then, K-V's competitors Sandoz (the generics arm of global giant Novartis (NVS)) and Andrx Pharmaceuticals (the generic arm of Watson) have been working to develop their own versions of Toprol.

4. Lamotrigine

Launched: February 2005
2008 sales: $671 million
Branded equivalent: Lamictal, by GlaxoSmithKline (GSK), 2008 sales $1.6 billion

It took a long time for Teva to secure approval from the FDA for their generic copy of GlaxoSmithKline's bipolar and epilepsy drug Lamictal. Lamictal is one of the top-selling branded drugs in the United States, with around $2.2 billion in annual sales. After three years of legal wrangling, Teva won the battle in 2005 -- though Teva also lost a suit last year trying to bar GSK from producing a branded non-chewable version of Lamictal, saying that it violated the previous agreement. Even so, lamotrigine sales brought in $671 million for Teva and other generic drugmakers in 2008.

5. Risperidone

Launched: September 2008
2008 sales: $610 million
Branded equivalent: Risperdal, by Janssen, 2008 sales $2.1 billion

As with top-seller fentanyl, Mylan also took on Janssen-- founded by the eponymous Dutch scientist who invented antipsychotic drug Haldol -- in mental-illness drugs. Mylan released a generic version of Janssen's Risperdal Oral Solution, which treats schizophrenia and mania associated with bipolar disorder. Though the generic drug was approved for sale in September 2008, voiding an exclusivity agreement held by Teva, Mylan and co-developer Dr. Reddy's Labs (RDY) plan to ship it soon. Expect risperidone to move up the best-seller ladder.

6. Omeprazole

Launched: July 2008
2008 sales: $609.8 million
Branded equivalent: Prilosec, by AstraZeneca, 2008 sales $1.1 billion

Prilosec, AstraZeneca's juggernaut small-intenstine cancer treatment, received its first generic challenge from Andrx, which developed a generic version in 1998. (Andrx is now a division of Watson, which acquired it in March 2006 for $1.9 billion.) However, AstraZeneca sued to stop the release of the drug and won, forcing Andrx to wait until AZ's patent expired. Once it did, in 2001, several generic drug producers secured FDA approval for their own versions of omeprazole, launching it into the ranks of the top sellers.

7. Azithromycin

Launched: November 2005
2008 sales: $599 million
Branded equivalent: Zithromax, by Pfizer, 2008 sales $429 million

Generic drug companies aren't just persistent -- they're fast, too. When Pfizer's patent on Zithromax expired on November 1, 2005, Teva and Sandoz wasted no time in launching their generic equivalent, azithromycin. They both received FDA approval two weeks later and launched their products for sale the same day. Zithromax was the single most prescribed antibiotic at the time, but after its patent expired, Pfizer shifted its promotional focus away from the drug and towards Zmax, a similar antibiotic taken in just one dose instead of several times a day.

8. Budeprion

Launched: December 2006
2008 sales: $521 million
Branded equivalent: Wellbutrin, by Biovail (BVF), 2008 sales $579 million

Where there are generic drugs, there are lawyers. Biovail tried to avoid the coming generic onslaught for its antidepressant Wellbutrin by launching an extended-release version of the drug, called Wellbutrin XL, in August 2003. However, Taiwan-based Anchen filed a generic patent for the XL version, too. Biovail succeeded in suing to delay the release for 30 months, but a judge ruled in 2006 that Anchen could proceed. So Biovail took its case to the FDA -- but the FDA also approved Anchen's generic version. Anchen signed an agreement with generic competitors IMPAX Laboratories (IPXL) and Teva to jointly produce the drug. Now they're embroiled in a lawsuit alleging that the generic version doesn't work as well as branded Wellbutrin XL.

Shire today reported positive results from the first of three Phase III studies of velaglucerase alfa, its enzyme replacement therapy in development for the treatment of Type 1 Gaucher disease. The Company also announced that the U.S. Food and Drug Administration (FDA) has accepted its treatment protocol for velaglucerase alfa and that Shire has begun its rolling submission of the New Drug Application (NDA) for velaglucerase alfa allowed under the Fast Track process.

http://finance.yahoo.com/news/Shire-Reports-Positive-prnews-2267057375.html?x=0&.v=1

Invega Sustenna will hit Risperdal Consta very hard and quite quickly (I believe it will sell better in a couple of years), in the depot antipsychotic market.

Shire is in the same boat with PLX #msg-39309833

Genentech/Biogen 2nd Generation Anti-CD20

I think you'll find the story here:

http://www.gene.com/gene/pipeline/status/immunology/ocrelizumab/

And the arbitration panel decision here:

http://www.gene.com/gene/news/gne_biib_arb.html

GENZ - the Allston plant saga

Key word in your question is 'satisfy', meaning - will the FDA be satisfied with Cerezyme and Fabrazyme that were produced before reinspection? I think it will cause the reinspection is probably more about the manufacturing issue detailed in a warning letter that was issued in Feb and not about the viral contamination. Key question is - when. Of course GENZ will eventually get these issues taken care of, but meanwhile, they are losing time, money, and credibility and competitors are enjoying a tailwind.

Latisse sales did not improve much from last quarter, but guidance for the year was raised.

GENZ management didn't think the FDA would want to reinspect the Allston facility again, but the FDA informed them that reinspection will be required:

http://www.reuters.com/article/marketsNews/idINN3143144420090731?rpc=44

FDA's Psychopharmacologic Drugs Advisory Committee (PDAC) voted unanimously in favor of SAPHRIS(asenapine) sublingual tablets as effective and safe for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults and in favor of youth in acute treatment of schizophrenia in adults. SAPHRIS could be the first psychotropic drug to be approved initially for both of these indications.

GENZ really needs the 4000L facility in Belgium to be approved since the Allston facility will no longer produce Myozyme/Lumizyme only Cerezyme and Fabrazyme, so if something goes wrong there you'll get your big hit.
On being aggressive - PLX people can tell you how aggressive GENZ can be.

Elron Electronic Industries Ltd. (NASDAQ:ELRN) (TASE:ELRN) yesteday announced that Medingo Ltd., a group company held 92% by Elron and its subsidiary RDC - Rafael Development Corporation Ltd., has received an informal notice, by electronic mail, that the Food and Drug Administration ("FDA") has granted clearance to market its Solo MicroPump Insulin Delivery System in the United States.

http://www.elron.com/uploaded/28%2007%2009%20PR%20Medingo.pdf

I was wondering why it wasn't on the top 8 list but assumed it was no longer considered "top" after it went off patent...

But the answer is a product that had 1996 sales of about $200M not $1.1B :(

It did only $112M in 1996.

last try - CEFZIL (oral cephalosporin) made around $200M in 1996.

Why Can Some Patients Get Free Drugs While Others Can't?

http://www.businessweek.com/lifestyle/content/jul2009/bw20090723_645748.htm

Many pharmaceutical companies offer free drugs, but critics complain such Patient Assistance Programs don't go far enough

By Diana Holden

Six years ago, Carla Miller was an active woman who enjoyed outdoor activities such as camping. Then things started to go wrong. "I just had tremendous pain that would kind of come and go," she says. "It started in my knees and then it moved to my hands and feet." She was diagnosed with rheumatoid arthritis, an autoimmune disease that attacks the joints. Two years ago Miller, now 53, discovered she also had a rare disease that affects her lungs. "If I moved too fast or lifted a heavy object I would become short of breath," says the former office worker. "I tried to work and would become very ill and had to go home."

When Miller's doctor suggested Humira, an injected medicine manufactured by Abbott Laboratories (ABT) for her arthritis pain, she didn't think she could afford the nearly $300 co-pay. Her doctor suggested applying for a co-pay assistance program through the pharmaceutical company that makes the drug. She applied and received a card in the mail with which to purchase her medication. "They called and said I was approved and that my co-pay was going to be zero," Miller says. "I couldn't take [Humira] without it."

Most large pharmaceutical companies offer financial support, and some help underinsured patients through co-pay programs. Many states offer assistance, too. "There's still a lot of people who don't know about [these programs]," says Dr. Richard Sagall, the president of NeedyMeds.org. His Web site compiles information about patient assistance programs (PAPs). "Some of the companies give away very expensive drugs easily." Sagall started the site a dozen years ago, when he was a family and occupational physician in Bangor, Me. He found out about the programs and decided to put his recently learned Web site designing skills to use. "I thought I was a pretty socially aware person, but I hadn't heard of them," he says.

Complicated Forms

Sagall warns that it may not be easy for some people to apply for the programs. "There are other companies that are very difficult to work with," he says. The application forms can be complicated, and patients might be rejected "if you forget to dot an i or cross a t." Still, "It is free medication for those who can't afford it," he says.

For Miller, who lives near Tampa, it was a godsend. She had been laid off from work because she couldn't work full-time and qualified for disability assistance more than a year later. Her husband, a plumber, was laid off last year and is still looking for work.

What's the best way to start the process? First, talk to physicians, who should be aware of these programs. Needymeds.org, pparx.org, and rxassist.org all assemble information about PAPs. States post information online about financial assistance for residents. It takes patience and persistence to navigate the system, but for those who are willing to make the calls and do the research, the benefits can be immense.

Easier to Qualify

The recession has had an effect on many people's ability to pay for their prescriptions. Some companies are responding with improved payment options. Merck (MRK), which makes such common drugs as Singulair for asthma and Januvia for diabetes, increased the amount of total annual income a family can make and still qualify for free medication in March. Individuals making less than $43,000 and families of four making less than $88,000 now make the cut. Over the last seven years, Merck says it has helped 1.7 million patients with $1.9 billion of medicine. Merck made $23.85 billion in worldwide sales last year.

Biogen Idec (BIIB) has a payment plan for two of its multiple sclerosis drugs, Avonex and Tysabri. "We are committed to helping patients, and that commitment is evident in the $140 million of financial assistance we provided in 2008," spokesperson Shannon Altimari said in an e-mail. That accounts for 5% of the $2.79 billion in revenue that the company made from the two drugs in 2008.

Pfizer (PFE) announced a program in May called Maintain that provides free medication to unemployed patients who lack prescription drug coverage. Maintain is one of several patient assistance programs that the company offers.

Chicago-based Abbott Laboratories, which makes Miller's Humira, has provided that medication to patients in need since it came onto the market. The company introduced a Humira Protection Plan in March that helps reduce co-pays for insured patients to $5 per month. "The plan was really a response to patient and physician feedback that they needed more support," says Abbott spokesperson Elizabeth Hoff. The company earnings release says it gave out $255 million of free medicine last year and made $29.5 billion in sales. Total U.S. sales for Humira in 2008 were $2.25 million, but the company does not break out how much was given away.

Some people say that these offerings avoid the real problem. Larry McNeely, a health-care analyst at Washington (D.C.)-based U.S. Public Interest Research Groups (PIRG), says: "They're a Band-Aid on the gaping wound of unaffordable prescription drugs." He says that the high cost of medicine is a systemic problem that can only be fully addressed with legislation. "This is not a struggling industry. This is not automobiles," he says. "They're raking in profits."

Hit-Or-Miss for Patients

McNeely does not like the fact that PAPs are so hit-or-miss for patients. He worries that people have "tried to go through these programs and gotten lost in the shuffle." He advises patients to read the fine print and be careful not to get stuck without medication while waiting for approval.

Cynda Moss has experienced such problems. The 56-year-old retired teacher was diagnosed with Parkinson's disease in 1999, followed by lung cancer in 2001. Her income from social security and teacher retirement barely stretches far enough to cover her mortgage, medical bills, and other living expenses. "I have tried all sorts of avenues to see if I can get assistance with the drugs," she says. She called representatives for her pharmaceutical companies, Social Security, and Medicare. She has also followed several leads on the Internet. But because she has insurance, "they immediately tell me I'm disqualified," she says.

Moss' prescriptions can cost as much as $20 per pill, and her medical expenses are more than $500 per month. "There are times when I have had to forgo a pill or two here or there," she admits. Moss is not sure what the future holds for her.

While McNeely at PIRG believes that there needs to be a change in the system, he says: "If folks need assistance, don't give up. There are some potential options out there." Miller is one of the success stories. She says that because of her arthritis medication, "I have a chance at becoming a little bit more normal."

Clemizole's phase I trial started recruiting

http://www.clinicaltrials.gov/ct2/show/NCT00945880

Pretty much like they did with Pulmicort and Solodyn, they catch two birds - avoiding both legal risk and AG.