Drug Firms Advance Rapidly After Long Drought, but Treatments Are Pricey

Drug companies have scored a string of recent successes against advanced prostate cancer, ending a long drought during which there seemed to be few weapons to combat the disease.

In the latest evidence of progress, researchers reported Tuesday that an experimental drug from San Francisco-based Medivation Inc. extended survival by nearly five months in a 1,199-patient study. A second drug, a radiation-emitter being developed by Bayer AG and Algeta ASA of Norway, targeting prostate cancer that has spread to the bone, improved survival by nearly three months in a 922-patient study.

Results of both trials were released ahead of their presentation at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium being held this week in San Francisco.

If the drugs win approval soon from the Food and Drug Administration, it would mean that after decades of frustration, the pharmaceutical industry will have turned out five new treatments for advanced prostate cancer within just three years.

Those already approved within the past two years include Dendreon Inc.’s Provenge, Jevtana from Sanofi SA, and Zytiga from Johnson & Johnson.

The pharmaceutical industry is increasingly looking for ways to speed development of new drugs—including the realization that closer ties to academic researchers can aid in discovery. Medivation’s compound, called MDV3100, is notable for how it was developed—largely in the research laboratory of Charles Sawyers, a scientist at Memorial Sloan-Kettering Cancer Center with a track record in drug discovery.

Medivation expects to file its application with the FDA this year. Assuming all goes well, the drug could be on a track to win approval about five years after it was first tested in people. “By any standard, that would be considered very, very quick,” said David Hung, Medivation’s chief executive officer.

Also helping progress is a growing understanding of the biology of prostate cancer, a disease fueled largely by the male hormone testosterone.

The new treatments aren’t cures and individually their impact on survival is modest—in clinical trials each added a median of roughly three to five months to patients’ lives. Their high cost is likely to complicate adoption for many patients. Provenge, for instance, costs $93,000 for a course of three treatments while Zytiga’s price is about $5,000 for a monthly supply of pills.

But some researchers believe that the options will lead to new strategies where the drugs are used either sequentially or in combination to significantly extend survival. The new treatments are expected to cause the world-wide market for prostate cancer therapies to surge to $4 billion by 2015, according to Morningstar Inc., up from about $1 billion currently.

“The whole equation for prostate cancer is completely different,” said Christopher J. Logothetis, chief of genitourinary medical oncology at M.D. Anderson Cancer Center, Houston. “It is [now] among the solid tumors that should be considered highly treatable.”

All of this stands in contrast to just a decade or so ago when the disease was considered resistent to almost any treatment. Drug companies would say “nothing has worked in 35 years. Why are we going to throw our [new] drug at that?” said Bruce Roth, professor of medicine and an oncologist at Washington University, St. Louis. “Now we’re starting to see a payoff in the investment in research about the biology of prostate cancer.”

MDV3100 is a case in point. Dr. Sawyers, a Howard Hughes Medical Institute investigator, played important roles in the development of Novartis AG’s breakthrough leukemia drug Gleevec and a second-generation version called Sprycel from Bristol-Myers Squibb Co.

In the mid-1990s, while at University of California at Los Angeles, Dr. Sawyers became interested in why men with prostate cancer relapsed on hormone therapy—the standard treatments, which starve prostate tumors of testosterone, the primary fuel that makes them grow.

Conventional wisdom was that once a patient relapsed, the so-called androgen receptors—structures that protrude from tumor cells like a lock to attract the testosterone “key” that activates them and promotes tumor growth—were no longer driving the disease. Dr. Sawyers was skeptical. In a series of experiments with mice, he and his colleagues found that drug-resistant patients actually had elevated (not lower) levels of androgen receptors. Drugs were now activating them instead of blocking out the testosterone.

“It wasn’t destroying dogma, but it wasn’t what people expected,” Dr. Sawyers said. “It put a spotlight on the androgen receptor as a drug target.”

But he said he wasn’t able to persuade any drug companies to pursue the lead. So he teamed up with a chemist, Michael Jung, at UCLA to design a drug themselves.

Scouring patent databases, Dr. Jung discovered a compound made by the former French drug maker Roussel Uclaf that locked onto the androgen receptor about 100 times more strongly than the commonly used prostate-cancer drug, Casodex.

Using that drug as a template, and taking on a task normally performed by drug-industry scientists, Dr. Jung fashioned some 200 slightly different molecules, which the researchers tested against tumor samples in their own version of the drug industry’s high-volume screening technology. They came up with a promising candidate, tweaked it so it would be absorbed in the blood as a pill and then performed the key experiment—testing it in mice to see if it would shrink tumors.

“It did, very dramatically,” Dr. Sawyers said. But academic scientists aren’t positioned to take the drug across the “valley of death”—the chasm between a promising compound discovered in the lab and the work required to test it in humans, said Dr. Sawyers, who as an inventor of MDV3100 is entitled to royalties on any sales.

In 2005, Medivation agreed to license the drug. The company confirmed the researchers’ findings, tested the molecule and altered its formulation to make it suitable for humans, and filed an application with the FDA to start human studies.

Howard Scher, a veteran of prostate-cancer studies and chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer, agreed to run the research, which began in 2007. Aided by a 13-center research consortium group funded by the Defense Department and the Prostate Cancer Foundation and intended to speed development of medicines for the disease, researchers ultimately and rapidly enrolled 140 patients, with promising results.

In 2009, Medivation, in collaboration with Astellas Pharmaceuticals Inc. of Japan, launched a late-stage trial, the results of which Dr. Scher reported Tuesday.

Dr. Scher reported that the 800 patients treated with the drug had a median survival of 18.4 months compared with 13.6 months for those given a placebo. In addition, 54% of MDV3100 patients—compared to 1.5% of those on placebo—had a greater than 50% reduction in a marker called prostate specific antigen—an indicator of a positive response to the drug. Side effects included fatigue.

During a news conference to announce the findings, Nicholas J. Vogelzang, chairman and medical director of the developmental therapeutics committee of US Oncology, a cancer treatment company, called the results “unprecedented.” He added: “This is definitely going to change the way we take care of patients every day in the office.”

Dr. Scher said the first patient he treated four and a half years ago is still alive and on the drug. “That’s the beauty of a targeted agent,” he said.

For Medivation, the successful study contrasts with news two weeks ago that, along with partner Pfizer Inc., it was pulling the plug on development of an Alzheimer’s drug called dimebon after it failed to show benefit in a late stage, 1003-patient study.

http://online.wsj.com/article/SB10001424052970203920204577195372964538152.html

Winnipeg Wedding Catering

Cancun Puerto Morelos  Chichen Itza Tours Mexico

Dimebon Dimebolin Information Availability

US biotech firm Medivation (Nasdaq: MDVN) says that patient enrollment was completed at end November in the CONCERT study, a 12-month, Phase III clinical trial in patients with mild-to-moderate Alzheimer’s disease evaluating the potential efficacy of Dimebon (latrepirdine) when added to ongoing treatment with donepezil.

Medivation is conducting this study under its collaboration agreement with drug behemoth Pfizer (NYSE: PFE) which acquired rights the product in 2008 in a deal worth a potential $725 million ($225 million upfront) to the former company.

Dimebon – an old Russian antihistamine approved in that market in 1983 – had once been touted as a blockbuster drug for AD, with potential for anything between $1.5 billion and $5 billion annual sales. However, earlier this year, the majority of observers wrote it off after – somewhat unexpectedly – it failed to meet co-primary or secondary efficacy endpoints compared to placebo in two Phase III trials (The Pharma Letter March 4). After the disastrous results, Medivation’s shares cratered and have yet to recover from the beating they received.

Has received FDA feedback

“Completing patient enrollment in CONCERT is an important step forward for our Dimebon development program in Alzheimer’s disease,” said Lynn Seely, chief medical officer of Medivation. “Now that enrollment is complete, we expect to report top-line results from the CONCERT trial in the first half of 2012. We have previously received feedback from the FDA [Food and Drug Administration] confirming that we can use our Phase III CONCERT trial to complete our registration package for mild-to-moderate Alzheimer’s disease, provided that the results are robustly positive,” she added.

The international, randomized, double-blind, placebo-controlled Phase III CONCERT trial  enrolled 1,003 patients with mild-to-moderate AD at approximately 100 sites in the USA, Australia, New Zealand and Western Europe. Patients on a stable dose of donepezil were randomized to one of three treatment groups: Dimebon 20mg three times per day, Dimebon 5mg three times per day or placebo. Patients were required to be on treatment with donepezil for at least six months and at a stable dose of 10mg daily for at least four months prior to enrollment in the study. The primary endpoints are the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) and the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) – a measure of self-care and daily function.

http://www.thepharmaletter.com/file/100475/medivation-persists-with-dimebon-research-in-alzheimers-despite-earlier-failures.html

Puerto Morelos Dental Clinic

Puerto Morelos  Dentist  Crowns

Dimebon Dimebolin Information Availability

NEW YORK – Medivation Inc. stock more than doubled in value Thursday after the biotechnology company said a clinical trial of its experimental prostate cancer pill is ending earlier than expected because the study showed the drug worked.

Medivation, which does not have any products on the market, said an early analysis from the study showed that men who were treated with MDV3100 had median survival of 18.4 months. That was 4.8 months longer than men who were treated with placebo, and the company said the drug reduced patients’ risk of death by 37 percent. The late-stage clinical trial compared MDV3100 to placebo in 1,199 men with advanced prostate cancer whose disease had progressed despite chemotherapy and hormone treatment.

The company said it will meet with the Food and Drug Administration in early 2012 to discuss the regulatory pathway for the drug. Analysts said MDV3100 could be approved in early 2013 and annual sales could surpass $1 billion.

Shares of Medivation jumped $20.18 to $36.71 in afternoon trading Thursday.

MDV3100 is designed to block the signaling of androgen receptors, which play an important role in the growth of prostate cancer cells. Medivation and its partner, Astellas Pharma Inc. of Japan, are conducting another late-stage trial of the drug on men who have not received chemotherapy. They are running two mid-stage trials of MDV3100, one involving men who have not been helped by hormone treatment and one in men who haven’t received hormone therapy.

If it is approved, MDV3100 would compete with Johnson & Johnson’s prostate cancer pill Zytiga. The FDA approved Zytiga in April and European regulators cleared the drug in September. Rodman & Renshaw analyst Elemer Piros said that if MDV3100 is launched in early 2013, Zytiga will have a two-year head start. He said the two drugs have similar survival benefits, and said peak sales of MDV3100 could reach $1.2 billion a year.

However, Jefferies & Co. analyst Biren Amin said MDV3100 could have an advantage in survival. Patients treated with Zytiga had median survival of 4.6 months compared to placebo at the end of late-stage testing, but he noted that median survival was 3.9 months after an early analysis like the one Medivation and Astellas reported Thursday. Amin said patients treated with MDV3100 could also have greater survival when a final analysis is complete.

Medivation said full results from the study will be presented at a future scientific meeting.

Amin said he now expects annual sales of MDV3100 to reach $1.48 billion, while analyst Lucy Lu of Citi Investment Research said those sales could be more than $2 billion per year.

Shares of the San Francisco company peaked at $38.48 in morning trading. The stock had traded between $10.96 and $25.50 in the last 12 months. Shares were trading around $40 in late 2009 and early 2010, but the stock plunged in March 2010 after its other key drug candidate, an Alzheimer’s disease and Huntington disease drug called Dimebon, failed in a late-stage trial. Medivation is developing Dimebon through a partnership with Pfizer Inc., and the companies are continuing to test the drug.

http://www.cnbc.com/id/45152458

Winnipeg Acupuncture Therapy

Midtown Ford Winnipeg Blog

Dimebon Dimebolin Information Availability

Pfizer Inc. (PFE)’s plans to shed two businesses boosts the potential payoff for three experimental drugs moving toward regulatory review later this year.

Pfizer, the world’s biggest drugmaker, yesterday said it plans to sell or spin off its animal health and baby food divisions. The units may command a price of $22 billion, said Seamus Fernandez, an analyst at Leerink Swann & Co. in Boston. Pfizer Chief Executive Officer Ian Read has said he plans to use the proceeds to buy back shares and develop new drugs.

Read is giving new products led by the apixaban blood thinner, the lung cancer drug crizotinib and tofacitinib for rheumatoid arthritis added prominence within Pfizer’s revenue portfolio. Divesting the units — which generate $5.5 billion in annual sales, or 8 percent of the New York-based company’s revenue — also lets Pfizer sharpen its focus on developing the three drugs, which analysts surveyed by Bloomberg estimate may reach $3 billion in annual sales by 2015.

“In the next 3 to 6 months, there’s going to be a lot of pipeline news, and as Pfizer gets smaller the pipeline becomes more important,” said David Maris, an analyst with CLSA in New York. “This is a management team that is following through on what they said they would do, which is take a fresh look at the business and decide what is important and what is not.”

Pfizer declined 7 cents to $20.16 at 4 p.m. in New York stock exchange composite trading. The shares have climbed 36 percent in the past 12 months.
Sales to Fall

Pfizer loses patent exclusivity in November for its biggest product, the Lipitor cholesterol pill with $10.7 billion in sales last year. The drugmaker forecasts sales may fall as much as 8.3 percent in two years as the company’s new medicines fail to offset lower sales of Lipitor.

Crizotinib was accepted for priority review by the U.S. Food and Drug Administration, and the company expects clearance by year’s end, said Chris Loder, a spokesman. The drugmaker plans to seek approval of tofacitinib and apixaban by the end of the year, he said. Pfizer partners with New York-based Bristol- Myers Squibb Co. on apixaban.

“Pfizer’s late-stage pipeline is as well positioned as at any time in recent history,” said Christopher Schott, a New York-based analyst for JPMorgan Chase & Co., in a note to clients.
Wanting More

On Feb. 1, Read said he would review whether to divest four business areas that aren’t involved in developing new drugs, including the two now being shopped. Pfizer fell 2.7 percent yesterday, after the company said it will keep its established products and consumer health units with $12.9 billion in yearly sales. Some investors wanted the units sold to focus on higher- profit drug development.

Erik Gordon, a University of Michigan business professor in Ann Arbor, isn’t convinced Pfizer’s pipeline will pay off.

“Should Pfizer double its dependence on what it does worst: Get new drugs out the door?” Gordon, who studies the biomedical industry, said in an e-mail.

In 2006, Pfizer halted development of its torcetrapib cholesterol pill, a product designed to succeed Lipitor, after it failed to benefit patients in a late-stage study.
Development Failures

Last year, the drugmaker said its experimental Alzheimer’s drug Dimebon failed to help patients in a late-stage test. Analysts had predicted the product would generate $5 billion in annual sales. That same month, Sutent, approved for kidney and stomach cancers, failed in two studies to shrink breast tumors, and the experimental drug figitumumab didn’t help lung cancer patients.

Read, head of global pharmaceutical operations from 2006 until his appointment as CEO last December, said Pfizer needed to fix its “innovative core.” Fifteen research programs have been discontinued since last September and the budget to develop new medicines will be cut by as much as $3 billion in the next two years from $9.4 billion in 2010 to target experimental drugs with a greater chance of success, he said.

The units Pfizer is seeking to divest may be sold outright, or spun off as independent companies. Spinoffs evade a 35 percent capital gains tax and sometimes provide the best return for investors, said Adam Berger, head of mergers and acquisitions at Leerink Swann, in a telephone interview.

Still, the remaining parent company wouldn’t benefit from the added proceeds the way it would in a sale, he said.
Value to Shareholder

“It’s like a dividend; the value goes to the shareholder,” Berger said. “But Pfizer has been extraordinarily acquisitive, and sometimes if you’re a very large business it’s hard to grow from that base.”

Another option might be a sponsored spinoff in which investors buy a stake in the company, typically 20 percent, when the deal is announced, Berger said. That allows the parent company to share in proceeds from the divestiture, he said.

Pfizer acquired its nutrition unit in the 2009 purchase of Wyeth. The unit sells food replacement and supplement products in more than 80 countries, according to the company’s website.

Mead Johnson Nutrition Co. (MJN), the baby-formula maker that Bristol-Myers took public in February 2009, had sales of $3.14 billion last year, led by the Enfamil infant formula. The Glenview, Illinois-based company trades at 27 times earnings, almost three times the valuation of Pfizer, after a 188 percent surge through yesterday that beat the Standard & Poor’s 500 Index’s 63 percent rise, according to Bloomberg data.
Valuing Nutritionals

Applying Mead Johnson’s profit margins and share price valuation of 31 times net income to Pfizer’s unit, which had $1.87 billion in sales last year, would give Pfizer nutritionals a market value of about $8.4 billion, according to data compiled by Bloomberg.

Leerink’s Fernandez put the figure at about $10 billion for the nutritionals and said “demand would be high.”

Pfizer may fare better with an initial public offering for the animal health unit, which could value the unit at $10 billion to $12 billion, Fernandez said. He cited a “conversation with Pfizer” that suggested nutritionals would be sold and the animal health division may be spun off.

Pfizer had 28 divestitures completed in the last five years, with an average deal size of $1.8 billion, according to data compiled by Bloomberg. The biggest was the $16.6 billion sale of its consumer products business to Johnson & Johnson in June 2006. Pfizer sold Capsugel, a hard-capsules manufacturing business, to KKR & Co. in April for $2.38 billion.

Pfizer said it doesn’t anticipate making more announcements about the alternatives for the two units until sometime in 2012, and that any transaction may take as many as 24 months to complete.

http://www.bloomberg.com/news/2011-07-08/pfizer-unit-sales-add-payoff-to-pipeline-drugs-in-deal-seen-at-22-billion.html

For Sale Winnipeg used hondas accords honda for sale

Winnipeg Air Conditioning

Dimebon

Top-line results for Aastrom Biosciences‘ (Nasdaq: ASTM ) bone marrow-derived cellular therapy, ixmyelocel-T, look good. I’m not sure they were let’s-announce-the-conference-call-31.5-hours-in-advance-and-get-investors-excited good. But good nonetheless.

Ixmyelocel-T met its primary endpoint of delaying the time to first occurrence of treatment failure in patients with critical limb ischemia, an artery disease in which poor circulation can lead to amputations.

Treatment failure is a composite endpoint of major amputation

of the treated leg, all-cause mortality, doubling of wound size from baseline, and de novo gangrene. The first two are obviously clinically relevant. Who wants to lose a leg or die? The second two are important because the tissue loss is a predictor of eventual amputation.

Aastrom is saving the full data for a medical meeting, so we don’t know by how much the treatment failure was delayed. On one hand, it doesn’t matter too much; these are patients without any treatment options, so the fact that there is any kind of delay is what’s most important. But this is a phase 2 trial, so the magnitude of the delay will help determine how easy it will be for Aastrom to meet its endpoint in phase 3 development.

There are plenty of examples where companies have taken drugs that looked like they were working in phase 2 and weren’t able to duplicate the results in phase 3. It happens a lot in oncology — Novartis‘ (NYSE: NVS ) lung-cancer treatment ASA404 comes to mind — but it’s not specific to cancer. Medivation (Nasdaq: MDVN ) crashed hard after its Alzheimer’s disease drug, dimebon, failed to live up to expectations. Ditto for Inspire Pharmaceuticals‘ cystic fibrosis drug, denufosol, which failed a phase 3 trial. In the latter case, denufosol had actually passed one phase 3 trial, proving that nothing is certain in drug development.

If ixmyelocel-T does meet its endpoint in phase 3, the Food and Drug Administration is likely to approve the treatment because Aastrom is getting a special protocol assessment, or SPA, from the agency. The SPA allows companies to get input on the trial design from the FDA, so the company knows that the agency is content with the endpoint, trial size, and statistical analysis. Aastrom thinks it has reached an agreement with the agency, but it’s waiting for the final approval before starting the phase 3 trial.

Getting started with the phase 3 trial quickly is important, but investors will want to be certain they check the full phase 2 data when it’s presented in the fourth quarter.

http://www.fool.com/investing/high-growth/2011/06/02/the-drug-works-but-by-how-much.aspx

Winnipeg Acupuncture

Winnipeg Power Vac Services Duct Cleaning

Before a new, experimental drug is tried in humans, it’s put to work in test tubes and then animals. Once it’s ready for human trials, it’s tested in three distinct phases.

The Phase I trial is conducted with a limited number of subjects, usually fewer than 50. In cancer trials, the drug will be given to patients, sometimes as a last resort. For drugs targeting many other diseases, they’re given to healthy volunteers so doctors can better understand how the drug reacts inside the human body.

If a drug is deemed safe after this period, the company will proceed to Phase II. This trial usually consists of a few dozen to several hundred patients receiving varying dosage levels of the particular drug.

The data that’s considered most accurate is from a trial that’s “double blind” (neither the patient nor the doctor know if the patient has received the drug) and placebo controlled (compared to a placebo or standard of care). Few Phase II trials are double blind and placebo controlled.

In Phase III, companies test hundreds to thousands of patients. If the data proves that the drug is safe and effective, the company will usually apply for approval.

Naturally, the more patients who take part in a trial, the greater the chance the drug fails. For example, the drug may not work, or there may be unexpected side effects. This is especially common in cancer trials, where the response rates are low, even with approved drugs.

Positive results in Phase III can push a stock higher as investors begin focusing on approval and the sales and profits that could follow. However, it doesn’t always work that way. The Food and Drug Administration (FDA) for one reason or another has rejected many drugs with seemingly strong Phase III results. This can crush investors who followed a drug stock all the way to the end.

For example, MannKind Corp. (Nasdaq: MNKD) has seen its stock rise and fall sharply several times. Investors got their hopes up on the company’s inhaled insulin product Afrezza, only to see the FDA reject it time and again over safety issues.

This is one reason why Phase II is the real sweet spot for biotech investing.

Phase II Trials: A Profitable Time to be Involved in Biotech Investing

Phase II is often the most profitable time to be involved in a small cap biotech stock. Many times, Phase II results are positive. Sometimes it’s because the drug works. And other times it’s because the trial is rigged to provide positive results.

For example, Cel-Sci Corp. (AMEX: CVM), a company that stirs passion (both positive and negative) among biotech investors, ran a Phase II study on the head and neck cancer drug Multikine. However, rather than test the drug against other existing treatments, Multikine was given along with an existing treatment.

At the end of the trial, Cel-Sci boasted of a 12% complete response rate. But it was impossible to determine if the patients who had a complete response saw their tumors disappear due to Multikine or due to the other treatment.

So, why would a company do that?

To show good results in the hopes of raising additional capital.

There also are times when the science is conducted properly and Phase II claims are valid, but the drug isn’t able to replicate results in a Phase III trial. Remember, a Phase II trial usually contains a much smaller sample size, which can easily distort results.

Very often, when a company reports strong Phase II results, the stock takes off, as it is the first real indication that it might be approvable. Investors get excited; potential partners begin sniffing around; and the media begins to cover the drug’s potential. Even though at this point things are just starting to get promising, it’s often a great time to take the money and run.

Phase III, on the other hand, is fraught with risk. These trials are expensive to run, and there’s no guarantee that the drug will again show strong results. For example, there have been some instances where the drug replicated its earlier results, but there was a stronger than expected response from the placebo group, narrowing the difference that the drug made and making it appear less effective.

Phase II Takes Off and Fails in Phase III

There are many instances in which stocks took off during or after Phase II results, but then experienced major losses when the drug failed in Phase III.

A few real world examples – my subscribers made money on Medivation Inc. (Nasdaq: MDVN) despite a disastrous Phase III trial that resulted in the stock plummeting.

Medivation had a drug for Alzheimer’s called Dimebon. The Phase II results were outstanding. They showed a slower deterioration and fewer side effects than the existing therapies, including Pfizer Inc.’s (NYSE: PFE) Aricept. Despite skeptics’ doubts, the stock ran in anticipation of Phase III results. If the data was strong and the drug got approved, it would likely be an immediate blockbuster.

After the stock doubled, I recommended that subscribers take half of their profits off of the table. So with investors now playing with the “house’s money,” we waited for the Phase III results.

It turns out, the drug didn’t work.

The stock got crushed, and we sold out our remaining position. But because we had sold half at a 100% profit, we still pocketed a 37% gain. That’s not bad for a failed drug.

If The Smart Money Leaves… Take Your Profits and Follow

There have been several other instances where something similar has occurred. We made a 102% gain on Delcath Systems Inc. (Nasdaq: DCTH) and a 42% gain on MELA Sciences Inc. (Nasdaq: MELA), despite FDA rejections.

Although in these cases the Phase III trials were not deemed a failure, the FDA has rejected the applications for approval until more questions are answered.

Lastly, after positive Phase II results, you sometimes see the early investors and the venture capitalists exit the position. They’ve made their money and don’t want to stick around for the risky Phase III. If the smart money is leaving, it may be a good idea to follow them out the door.

There’s nothing wrong with hanging around and seeing if a small biotech company can get the ball across the goal line and get its drug approved. But considering that less than half of all drugs in Phase II actually make it to the market, it’s a smart idea to take profits along the way when you can.

http://moneymorning.com/2011/04/20/biotech-investing-phase-ii-is-the-sweet-spot/

Winnipeg Acupuncture

Medivation Inc. (MDVN) reported a loss of 16 cents per share in the third quarter of 2010, narrower than the Zacks Consensus Estimate of a loss of 21 cents and the year-ago loss of 42 cents. Lower expenses led to the narrower loss. Revenues for the quarter were $14.4 million, well below the Zacks Consensus Estimate of $16 million. Revenues were $16.3 million in the year-ago period.

Quarter in Detail

Revenues consisted of partial recognition of the non-refundable upfront payment of $225 million received from Pfizer (PFE) in October 2008 and $110 million received from Astellas in late 2009. The upfront payments are being recognized on a straight-line basis, while the Pfizer payment will be recognized through the fourth quarter of 2013, the Astellas payment will be recognized through the fourth quarter of 2014.

Operating expenses declined 23.6% to $21.1 million. Research and development expenses declined 27.4% to $15.6 million primarily due to decreased clinical activity in the Dimebon program. This was partially offset by increased clinical trial activities in the MDV3100 program.

SG&A expenses declined 9.6% to $5.5 million primarily due to the 20% workforce reduction implemented in March 2010, the termination of office leases, and lower intellectual property expenses related to Dimebon. Medivation expects its cash balance to be sufficient to finance operations beyond 2012.

Pipeline Update

Medivation provided an update on its pipeline candidates. The company expects to report top-line results from its phase III HORIZON study in the first half of 2011. The study is being conducted with Dimebon for the treatment of Huntington disease. Medivation will request a pre-New Drug Application (NDA) meeting with the US Food and Drug Administration (FDA) if results are positive.

Meanwhile, Medivation continues to evaluate Dimebon in the CONCERT study, which is being conducted with patients suffering from mild-to-moderate Alzheimer’s. Robust results from this study along with data from an earlier study could be enough to support Dimebon’s approval for mild-to-moderate Alzheimer’s disease.

Medivation and partner Astellas are looking to complete enrolment for the phase III AFFIRM study (advanced prostate cancer) by mid-Nov 2010. The companies initiated another phase III study (PREVAIL), which is being conducted in chemotherapy-naïve advanced prostate cancer patients.

The companies also intend to commence two new studies with MDV3100. While one trial will be a head-to-head phase II study between MDV3100 and AstraZeneca‘s (AZN) Casodex (bicalutamide), the other study (phase II) will be conducted in hormone-naïve patients. Top-line results from CONCERT and AFFIRM should be out by 2012.

We expect investor focus to remain on the HORIZON study results, which are expected in the first half of 2011.

http://www.benzinga.com/10/11/602409/narrower-loss-at-medivation-analyst-blog

Dimebon

http://www.dimebonalzheimers.com/

Mazda  Edmonton

Winnipeg Mainstay

At the request of the U.S. Food and Drug Administration, Pfizer Inc. has halted mid-stage clinical studies of what would have been the world’s first biologic pain reliever for back and diabetes-related discomfort.

The news about the once-heralded drug tanezumab, released Monday shortly after the stock market closed, is yet another blow for Pfizer’s new-drug pipeline as the company faces the November 2011 expiration of the patent on Lipitor, the world’s leading medicine, with sales of more than $11 billion last year. It also is disappointing news to Pfizer’s drug-development team in New London, which has been involved in setting up and analyzing tanezumab’s clinical studies.

Just last month, Pfizer had presented positive data on tanezumab, demonstrating the injectable antibody’s effect on reducing knee pain in osteoarthritis patients. A week later, New York-based Pfizer, which has its biggest worldwide research site in Groton, announced that the FDA had asked it to stop a late-stage study of tanezumab in osteoarthritis patients because some people using the experimental drug wound up needing joint replacements.

The FDA’s latest request “follows further consideration of reports of adverse events in osteoarthritis patients,” Pfizer said in a statement, citing “the agency’s concerns regarding the potential for such events in other patient populations in which the compound is being studied.”

Pfizer said it continues to study tanezumab as a pain reliever for cancer patients and in other groups with unmet medical needs.

Pfizer’s stock price was down 18 cents, or about 1.2 percent, at the end of trading Monday, finishing at $14.55 a share.

The latest drug-testing closure for Pfizer follows several years of bad luck and bad decisions regarding some of the company’s most-promising medicines.

Among the most spectacular failures have been heart medication torcetrapib, once heralded as a potential successor to Lipitor but, after an $800 million investment in research during clinical trials, found to result in excessive deaths; the inhaled insulin Exubera, which never caught on with patients and cost the company nearly $3 billion, and the Russian-born antihistamine Dimebon, which had shown excellent results in midstage trials on Alzheimer’s disease but utterly failed in clinical tests that ended earlier this year and cost Pfizer at least $300 million.

Tanezumab was one of the most promising drugs being developed by San Francisco-based Rinat Neuroscience Corp. when Pfizer bought the company four years ago for a reported $500 million. A pipeline review announced by Pfizer just last year put tanezumab as among its top drug prospects.

Earlier studies of the drug showed significant pain relief and no major health risks.

“Repeated dosing with this compound gives sustained pain relief,” Northwestern University researcher Thomas Schnitzer told the website MedPage Today last fall.

But naysayers have questioned the potential market for tanezumab, wondering if an injectable biologic pain reliever would be embraced. Biologic medicines are made with live organisms.

Pfizer indicated it has not given up on tanezumab. It said the shutdown of its latest clinical trials would have no effect on the employment of local scientists.

“Pfizer will continue to work with the FDA to reach a common understanding about the appropriate scope of continued clinical investigation of tanezumab,” the company said.

Drug makers’ attempts to find treatments for Alzheimer’s disease have produced scant results and a long string of busts. Now a broad effort is under way to learn something from those failures.

A group of major pharmaceutical companies will share pooled data from failed clinical trials in an attempt to figure out what is going wrong in the studies and what can be done to improve drug development.

In the first wave, data from 4,000 patients across 11 failed Alzheimer’s-drug clinical trials from Johnson & Johnson, GlaxoSmithKline PLC, AstraZeneca PLC, Sanofi-Aventis and Abbott Laboratories will be publicly available as of Friday.

Data from additional drug makers and the National Institutes of Health will be added in the future. The coalition aims to create similar pooled databases for Parkinson’s disease and tuberculosis, said Marc Cantillon, executive director of the Coalition against Major Diseases, which spearheaded the project, funded by the Food and Drug Administration and Science Foundation Arizona.

The data will be available to all the participating drug makers, as well as outside researchers with a valid scientific question, Dr. Cantillon said.

“Companies said they’re running into a stone wall with Alzheimer’s and Parkinson’s,” said Ray Woosley, chief executive of the Critical Path Institute, which oversees the coalition. “We really believe drugs are failing because we honestly don’t understand the disease.”

The hope is that this large database will help answer some questions that individual trials with just a couple of hundred patients can’t answer, such as how the disease progresses and whether there are differences in subgroups in the population.

“Innovation no longer happens solely in one company’s lab,” said Frank Casty, AstraZeneca’s vice president of technical evaluations. “It is happening through constant interaction between scientists in the biopharma industry, patient advocates, academia and government.”

For the FDA, the project is something of a counter to criticism that it has been slowing down drug development because it is too focused on patient safety as opposed to on how well a drug works. Rather than debate whether the benefit-risk calculation for new drugs should be changed, the FDA wanted to help the industry develop better methods for determining if drugs are safe and effective, according to Mark McClellan, a former FDA commissioner who helped develop and support the coalition.

“The whole point of this type of effort is to get out of that debate,” Dr. McClellan said.

FDA Deputy Commissioner Joshua Sharfstein said, “I think the FDA recognizes that one thing that can accelerate drug development is sharing information that is relevant to a disease.”

If the database works as hoped, it may enable drug makers to build more sophisticated computer models to help design more efficient clinical trials that require fewer patients and less money, Dr. Cantillon said.

With current studies, if the results show no difference between patients getting an experimental treatment and those getting a placebo, it often isn’t clear if the drug failed or if there was something wrong in the study design that prevented the effect from being picked up in the statistical analyses.

The most recent example is Pfizer Inc.’s Dimebon, originally a Russian cold medicine that had shown promise in treating Alzheimer’s patients in a small, Russian-based trial several years ago. But, a larger, multinational late-stage study recently showed that the drug had no effect on this new sample of patients.

“People are left wondering why it didn’t work,” said Dr. Cantillon.

If a better model could be developed to predict which patients would respond, “it’s possible” that Pfizer could go back and look at Dimebon’s response in those subgroups, he said.

A Pfizer spokesman said the company “is participating in a number of public-private partnerships with governments, independent medical and scientific groups, companies and advocacy groups. Collaborations such as these can lead to more treatment options and better care for patients and the people who care for them.”

http://www.dimebonalzheimers.com/

Dimebon Over Counter Treatment

One Hour Canada

Furnasman New Homes

Furnasman Winnipeg

Drug Trials Test Bold Plan to Slow Alzheimer’s
By GINA KOLATA

Marilyn Maldonado is not quite sure why she is at the Memory Enhancement Center in the seaside town of Oakhurst, N.J.

“What are we waiting for?” she asks. About 10 minutes later, she asks again. Then she asks again.

She is waiting to enter a new type of Alzheimer’s drug study that will, in the boldest effort yet, test the leading hypothesis about how to slow or stop this terrifying brain disease.

The disease is defined by freckles of barnacle-like piles of a protein fragment, amyloid beta, in the brain. So, the current thinking goes, if you block amyloid formation or get rid of amyloid accumulations — plaque — and if you start treatment before the disease is well under way, you might have a chance to alter its course.

On Tuesday, that plan got a new push. The National Institute on Aging and the Alzheimer’s Association proposed new guidelines for diagnosis to find signs of Alzheimer’s in people who do not yet have severe symptoms, or even any symptoms at all.

The guidelines are needed for the new approach to Alzheimer’s drug development. Just about every pharmaceutical company and many biotechnology companies have experimental drugs to block amyloid — there are more than 100 in the pipeline. And the companies would like to show that if they give their drugs early, they can slow or stop the disease.

That is the ultimate goal for the drug in the study Mrs. Maldonado wants to enter, sponsored by Bristol-Myers Squibb. The company is, for the first time, testing such a drug in patients who, on evaluation with memory tests and new brain scans and tests for amyloid in cerebrospinal fluid, seem to be in a very early stage of Alzheimer’s. The idea is to attack the disease when there may still be time to stop the worst brain cell death.

But there is a problem. The Food and Drug Administration says it needs to know not just that plaque was reduced or even that it disappeared, but that those who took a drug ended up with better memory and better ability to think and reason as compared with those who did not take the drug.

Alzheimer’s, though, progresses so slowly that showing that a drug, started early, affects symptoms can take far longer than companies can afford to wait.

There is reason not to accept other forms of proof, like scans or cerebrospinal fluid that show changes in amyloid in the brain, the F.D.A. says. The agency has approved drugs for diseases, including sudden death from heart arrhythmias, on the basis of tests that showed symptoms, like heart rhythms, improved. Then it turned out the drugs did not affect the course of the disease and, in the case of the heart drugs, actually hastened death.

So the Alzheimer’s field is poised at an agonizing point — ready to move forward with new methods of diagnosis and drugs that might modify the course of the disease, but without proof that blocking amyloid actually makes a difference.

In the meantime. Bristol-Myers is trying a two-pronged strategy to gain faster approval. It is starting treatment early, but not so early that patients are a decade or more away from Alzheimer’s. And as it looks for effects on symptoms like memory and reasoning, the company will be tracking what happens to amyloid in the brain, hoping to show symptoms improve or no longer worsen as plaque formation slows or stops.

It is a gamble for the company, because even people with fairly mild symptoms may have too much brain damage to be helped. But it is a strategy that makes sense, said Dr. Dennis J. Selkoe, a Harvard researcher who is not affiliated with the study.

“In my view, the sweet spot for amyloid-lowering trials is mild Alzheimer’s disease,” Dr. Selkoe said. “As soon as one of those trials shows benefit, everyone will move to prevention trials,” he said. “They will begin treating before there are symptoms.”

Mrs. Maldonado may be one of the pioneers.

The Amyloid Hypothesis

Considering how important a medical problem Alzheimer’s is — afflicting 5.3 million Americans, the seventh-leading cause of death, and devastating and bankrupting families — it took a surprisingly long time to be recognized as a disease at all. And it took longer still to reach any kind of agreement on its cause.

Dr. Paul Aisen, an Alzheimer’s expert at the University of California, San Diego, remembers well the old days, in the late 1970s. He was in medical school, studying to be a geriatrician. There was no discussion of Alzheimer’s disease.

Ever since it was described by Dr. Alois Alzheimer in 1906 as a “peculiar” disease in a 51-year-old woman, doctors had considered it an oddity, a rare illness of middle, not old, age. Old people who lost their memory and ability to reason and care for themselves were said to be “senile.” That word did not refer to any specific disease like Alzheimer’s. Senility, Dr. Aisen said, was “what might happen when you got old.” And “there was nothing you could do about it.”

Then, in 1976, doctors’ eyes were opened by an editorial in Archives of Neurology by Dr. Robert Katzman, a neurologist. Alzheimer’s, he wrote, is not rare — it is common. It can arise in old age. And it is a leading cause of death and, Dr. Katzman said, a disease whose origin could be determined and whose course might be stopped.

Neurologists took note. But it was 20 years before there were any drugs for Alzheimer’s, and the four approved so far treat only symptoms, modestly and temporarily improving memory, for example, and do not affect the relentless brain cell death.

In the meantime, researchers came upon an exciting target for a drug. They discovered two enzymes that snip pieces from a large protein protruding from brain cells. The result is toxic fragments of a substance known as amyloid beta peptides. Those shards accumulate as plaques on the brain. One way to prevent plaques might be to block one of those crucial enzymes.

Just about every drug company got to work.

They had long suspected amyloid beta was a key player in the genesis of Alzheimer’s, but until they found the enzymes researchers had no way to block it. Amyloid beta itself might be injuring nerve cells or the plaques, made of accumulations of amyloid beta, could be the culprits. But whichever was true, three lines of evidence pointed to amyloid beta: rare gene mutations that lead to its overproduction cause Alzheimer’s in middle age. Down syndrome also causes overproduction of amyloid beta, and people with Down always get Alzheimer’s. And when scientists put the rare mutated genes that cause Alzheimer’s into mice, the mice developed plaques and memory problems.

The logic was not airtight. Scientists note that older people with typical Alzheimer’s often have something else wrong in their brain — damage from mini-strokes, for example. Perhaps some of these other conditions set off waves of cell death independent of amyloid beta.

But over the years, researchers say, what has become known as the amyloid hypothesis — the notion that overproduction or reduced clearance of amyloid beta is a cause of the disease and blocking amyloid beta could stop it — dominated their thinking.

“Ninety percent of us in the field believe it is correct,” Dr. Aisen said.

An Antibody Approach

Testing of the amyloid hypothesis began a few years ago with two experimental anti-amyloid drugs, homotaurine and tarenflurbil.

Patients who took them did not improve.

But, some researchers asked, was that a fair test? The first drug was not very potent, and little of the second reached the brain. And it was not clear whether either was really affecting amyloid because there were no direct measurements of plaques or amyloid beta protein.

The results, said Dr. Samuel E. Gandy, a professor of Alzheimer’s disease research at Mount Sinai School of Medicine, were “uninterpretable.”

Then there was the vaccine approach — immunize against amyloid beta and let the immune system clear plaque. It worked in mice and so, to great excitement, researchers tested it in patients. But a preliminary study was abruptly halted when 18 of 300 patients developed a brain inflammation. Two immunized patients who later died after reaching “severe end-stage dementia” had almost no plaque in their brains on autopsy — the vaccine had apparently cleared plaques but not noticeably affected their disease.

But that is not proof a vaccine would not work, said Dr. Selkoe, a founder of the company that did the study and a consultant to it. Two patients hardly constitutes a full analysis of the trial data, he says.

Now, the company, Elan, and its collaborators are trying a different tack. Instead of using a vaccine, they made an antibody to amyloid beta, a drug called bapineuzumab.

Some initial results were published in March. A new type of scan that can show plaques found the drug was removing them. But so far it is unclear whether patients are improving.

Johnson & Johnson, which partnered with Elan and its collaborator, Pfizer, says it will continue the study.

That makes sense, said Dr. Gandy, who is not part of the study.

“We have no idea how long we might need to treat,” he said.

Tough Road to Consensus

Dr. Russell Katz, director of the F.D.A.’s division of neurology products, is in a quandary about Alzheimer’s drugs. What, he must decide, should be the criteria for showing that a drug works?

Should the F.D.A. say it is sufficient to show that a treatment prevents or lessens the formation of plaque?

The agency is not ready to do that, Dr. Katz said.

“You only care if down the road the patient gets better,” Dr. Katz said. “What we are concerned about is approving a drug based on a lab test and being wrong about what happens to the patient clinically.”

With Alzheimer’s, Dr. Katz said, “the great fear is that maybe amyloid has nothing to do with the disease.” If that were the case, and the agency approved a drug that blocked amyloid formation, millions of healthy people could end up taking something useless or even dangerous. And because it takes so long for Alzheimer’s to develop, it could be decades, if ever, before anyone knew the drug did not work.

“It is a conundrum,” Dr. Katz said. “We all hope to get to the point in our understanding of the disease process where everyone in the field says: ‘Look. We know it now. Amyloid causes Alzheimer’s, and we have drugs that decrease amyloid.’ But we are not there yet.”

Bristol-Myers Squibb, though, is betting amyloid beta is the culprit. And it is betting it can show an effect in people who are in the early stages of Alzheimer’s.

Still, Dr. Aisen is concerned that even those patients, people like Mrs. Maldonado, might be beyond help. Treatment may have to start much earlier. So he is planning a large federal study to test amyloid-blocking drugs in people over 70 with normal memories but evidence of some amyloid accumulation. His criteria for success will not be the F.D.A.’s current one. Instead, he will ask whether the drugs slow the brain atrophy that is characteristic of Alzheimer’s and prevent amyloid from accumulating in subjects’ brains.

“If you think Bristol-Myers Squibb is going out on a limb, this is going farther,” Dr. Aisen said. If blocking amyloid beta and slowing brain atrophy are not accepted as sufficient evidence that a drug works, a study with normal 70-year-olds could end up taking 10 to 15 years to show an effect on the actual symptoms of Alzheimer’s.

After her scan that recent day, Mrs. Maldonado was entered in the Bristol-Myers study.

She is 82, a former school bus driver living in nearby Jackson with a diagnosis of mild memory impairment. She came with her son-in-law to the Memory Center that day, in black slacks and a flowered blouse, wearing a gold bracelet and gold rings. Her short white hair was fluffy, freshly washed. And she had a way about her, a joking demeanor, intended to disguise her forgetfulness.

Her brain, the scan showed, was riddled with plaque.

Dr. Joel Ross, who runs the Memory Center, told her the results.

“We found you are producing a sticky material called plaque,” he told her.

“Yeah,” she said.

“It’s coating some of your brain.”

“Yeah,” she said again.

“If you stay this way there will be a lot of it.”

“Yeah.”

“So we’re going to give you a drug that may clear it up.”

“Yeah.”

http://www.nytimes.com/2010/07/17/health/research/17drug.html?_r=1&th=&emc=th&pagewanted=print

Dimebon Online Pharmacy Canada

http:www.//dimebonalzheimers.com