Neurochem (NRMX): 2007 - Entscheidungsjahr? - 500 Beiträge pro Seite

[tippse]

erstaunlich, dass es zu nrmx hier noch keinen thread gibt - denn die firma ist mit ihrem flagschiff: "alzhemed" an einem der ganz großen biotech-themen dran: alzheimer!

... und das ziemlich nah: mit den worten des ceo, francesco bellini: "The summation of all our work and research for the last 12 years will happen in the next six months," - das heißt übersetzt: zulassungsantrag durch die fda und damit zugang zu einem milliarden-markt!

interessanter artikel hierzu in der online-ausgabe der "businessweek":
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JANUARY 8, 2007
SPECIAL REPORT

Decoding Alzheimer's
After a century, promising treatments at last—and whispers of a cure

Francesco Bellini hasn't been sleeping lately. The charged-up chairman of Neurochem Inc. (NRMX ) is just months away from finding out if a drug developed by his Quebec-based company can actually slow the course of Alzheimer's disease. A clinical trial of the drug, Alzhemed, will wrap up in January, with results expected in the spring. "The summation of all our work and research for the last 12 years will happen in the next six months," he says

Those 12 years have been focused on overcoming one of the toughest challenges in medicine: keeping Alzheimer's disease from slowly, relentlessly destroying the brain, something no drug has yet done. The data on Alzhemed have been promising but scant. In a 2002 study it stabilized the disease in nine patients over six months, but the small sample left plenty of specialists skeptical. Not Bellini, a scientist-entrepreneur who discovered one of the first effective treatments for aids. He bought a third of Neurochem and took the helm the same year the earlier Alzhemed trial was completed. "I started to feel very good about the drug as soon as I saw what it did for humans," he says.

Neurochem quickly moved ahead with a costly late-stage trial, enrolling 1,052 patients with mild to moderate Alzheimer's. There is plenty of debate in the Alzheimer's world over what the results of that trial are likely to be, but a recent follow-up of patients from the previous study found that four were still stable after four years on Alzhemed. In addition, Bellini says every patient who has completed the trial asked to continue the drug—a sign, he says, that it is helping. "I was expecting maybe 30% would ask, but 100%, that's remarkable."

It's not hard to understand why patients would want to continue: They are desperate for hope. Alzheimer's is a frightening trend for an aging population. One in 10 people over the age of 65 develops the disease. Over age 85, the odds rise to one in two. The diagnosis is an agonizing death sentence, as it takes anywhere from 3 to 20 years for Alzheimer's to kill—and it always does. The Alzheimer's Assn. estimates there will be 9 million Americans with the disease by 2020 and 15 million by 2050. If there are no disease-modifying drugs by then, the cost of care will top $1 trillion.

Whether or not Alzhemed works as hoped, its very existence is just one reason the outlook for Alzheimer's drug discovery is turning, finally, more positive than negative. A century after the disease was first identified, scientists are closing in on medicines that can safely delay or reverse its onset. The burden of proof doesn't rest solely on Alzhemed, either. Flurizan, a drug developed by Myriad Genetics Inc. (MYGN ), is also in a late-stage trial, with results expected next summer. A few years behind Alzhemed and Flurizan are promising treatments from Wyeth Pharmaceuticals (WYE ) and Eli Lilly & Co. (LLY ) that provoke an immune response against the disease. Nearly 60 other drugs designed to modify the disease are also in clinical trials, including one from AC Immune of Switzerland that caught the attention of biotech giant Genentech Inc. (DNA ), best known for its cancer treatments. Genentech just announced plans to invest $300 million for the rights to AC Immune's drug. "It's a whole new era," says Dr. Serge Gauthier, director of Alzheimer's research at McGill University's Center for Studies in Aging. "At least some of these medications are likely to work, and once we have disease-modifying drugs, we have opened the door to prevention."

It's particularly striking that the science is advancing despite a long-standing dearth of investment in Alzheimer's research. There are currently 4.5 million Alzheimer's patients in the U.S., and the direct and indirect costs of caring for them total more than $100 billion a year, making Alzheimer's the third most expensive illness after heart disease and cancer. Yet the federal government budgeted only $645 million for Alzheimer's research for 2007, $7 million less than the prior year. In contrast, $2.6 billion was allocated for research into HIV/AIDS, which afflicts one million Americans.

The massive funding pumped into HIV research led to predictable results: AIDS was transformed from a death sentence into a manageable disease in just 10 years. Scientists say the same could happen with Alzheimer's if there were a similar national will. "Look, if we doubled our research output it would halve the amount of time it will take to find a cure," asserts Dr. Leon J. Thal, director of the Alzheimer's Disease Research Center at the University of California, San Diego.

Certainly any disease could benefit from more funding, but with Alzheimer's the need for effective treatments is especially urgent. It is the only major cause of death in the U.S. where the numbers are getting worse, not better. That's because Alzheimer's is a disease of success. As people live longer and benefit from new treatments for common killers such as heart disease and cancer, the odds they will succumb to Alzheimer's increase. Proving the point, Los Angeles County just reported that deaths there from heart disease dropped 29% between 1998 and 2003, and from lung cancer by 19%. But deaths from Alzheimer's soared 220%.

Given the trend lines, any drug that ameliorates the disease is certain to be an instant blockbuster. Investment advisers Cowen & Co. (COWN ) calculate that if just a few of the medicines in clinical trials pan out, U.S. demand for Alzheimer's drugs could reach $10 billion to $15 billion annually, up from about $1.3 billion now.

The market will be even larger if these new drugs are used by millions of senior citizens with faulty memories, a condition called mild cognitive impairment (MCI) that significantly raises the odds of developing Alzheimer's. The hope of every drug developer out there is that a successful Alzheimer's treatment may be able to prevent the disease from occurring in these higher-risk patients. "The MCI market is huge—20 or 30 million people," says Neurochem's Bellini.

The changing outlook for Alzheimer's is particularly striking because, unlike heart disease and cancer, there has been no gradual evolution from good drugs to better. The Food & Drug Administration has approved only five medicines for the disease, led by Pfizer Inc.'s (PFE ) Aricept. All relieve only some memory loss, for some months, in some patients. Until recently, neither large pharmaceutical companies nor venture capitalists showed much interest in funding research into more effective drugs, given the low success rate. With no proven treatment, or even a proven cause, Alzheimer's research seemed just too risky.

The U.S. government has no plans to put together the equivalent of a moon shot to cure the disease. But a critical mass of committed scientists, philanthropists, and maverick entrepreneurs has come together and put forth new scientific approaches and new funding sources to push the field forward. The result: For the first time, scientists are beginning to whisper the word "cure."

PAST AND PRESENT
Rudolph E. Tanzi, a boyish-looking 47, ended up in Alzheimer's research in the early 1980s after he realized he probably wasn't going to make it as a rock star. Having recently graduated from the University of Rochester, he quit his band to work on the genetic causes of brain diseases at Massachusetts General Hospital. He earned a PhD from Harvard University, and in 1987 his team discovered a gene that plays a key role in the start of Alzheimer's, solving a central mystery of the disease.

Today, Tanzi is director of the Genetics & Aging Research Unit at Mass General's Institute for Neurodegenerative Disease, working with some 200 other researchers, several hundred mice, and his wife, Dora Kovacs, who studies the role of inflammation in Alzheimer's. Tanzi has started two companies to develop drugs based on his findings, written dozens of scientific papers, and still found time to pen a layman's history of Alzheimer's research, Decoding Darkness, published in 2000. "I can't imagine a more incredible puzzle to solve," he says.

The solution has been a long time coming. Alzheimer's was first identified at a medical meeting in Germany in 1906 by a Bavarian neurologist, Dr. Alois Alzheimer. He described a patient, Auguste D., whom he started treating for madness when she was 51. She died five years later, and when Dr. Alzheimer autopsied her brain he discovered it was riddled with sticky clumps and fibrous tangles. For the first time, dementia was classified as a distinct disease rather than a form of insanity, and there the science remained for 78 years.

It wasn't until 1984 that scientists figured out that those clumps are made of a protein found throughout the body called amyloid. The discovery gave birth to the amyloid hypothesis, which holds that the accumulation of amyloid plaque in the brain slowly destroys brain cells. This is still very much a theory. Some experts contend that the excess amyloid may instead turn out to be a by-product of some earlier disease process that already took hold of the brain. "Many in the field find the evidence behind the amyloid hypothesis compelling, but we can't exclude the possibility that other targets play an important role," says Dr. Richard A. Hodes, director of the National Institute of Aging (NIA). "It's critical that we not put all of our efforts in that domain."

Nevertheless, drugs targeting amyloid are much further along than any other approach because the amyloid process has been at least partially decoded. The gene discovered by Tanzi 20 years ago starts the process, creating a large protein called APP. Found in almost every cell of the body, APP sticks halfway out of the cell wall. Two scissor-like enzymes cut away a fragment of this molecule, which then floats away to facilitate communications between other cells. But for unknown reasons, these fragments sometimes go awry and become toxic.

In the brain, normal amyloid fragments are 38 to 40 molecules long. But in the mid-1990s scientists discovered that the wayward snips consist of 42 molecules. Those extra two molecules cause the amyloid fragment to fold in on itself until it looks like a bobby pin. As more and more bobby pins are formed, they become entwined, creating clumps called plaque.

The vast majority of Alzheimer's drugs in development target A-beta 42, as this overgrown fragment is known. There is wide variation in their methods, however. Some seek to reduce its production, while others try to keep it from accumulating into plaque. Tanzi and an Australian colleague, Ashley Ian Bush, came up with a "chelating" agent that washes A-beta 42 out of the brain before it can clump together.

Their drug is based on Bush's discovery that traces of zinc, copper, and iron prod amyloid to form into plaque. The two found a compound that removed those metals from the brain and caused amyloid levels to drop in mice. They then teamed up with a pioneering Alzheimer's scientist, Colin Masters, in 1997 to form Prana Biotechnology Ltd. (PRAN ) in Victoria, Australia.

Coming up with the money for a drug startup is never easy, and Alzheimer's is on the bottom of venture capitalists' to-do lists. But Bush had a deep-pocketed friend in Australia who was looking for a new adventure. Geoffrey Kempler, 50, CEO of Prana, made his millions by securing the Australian rights to the Aveda (EL ) line of beauty products. Fueled by a combination of "naiveté and enthusiasm," as he puts it, he spent a few million dollars getting Prana off the ground before its initial public offering in 2000.

Prana's metal-removing drug was tested in 36 patients in 2003, and it successfully lowered amyloid levels. But in April, 2005, problems with the drug's purity forced Prana to stop the program. The share price sank from $4 to $1 within days.

As it happened, Prana was working on a successor treatment designed to be safer than the first. Although still in shock over the blow to the market value, "we actually put our foot on the accelerator," says Kempler. The second drug successfully completed an initial safety study in 2005, and in December Prana started a larger trial with 80 patients in Sweden. If all goes well, the drug could reach the market in five years, says Kempler. The stock price, meanwhile, has risen to around $3 a share.

Tanzi is not counting on Prana alone. Alz-heimer's is such a complex disease that most experts anticipate giving patients a cocktail of drugs, much as they treat AIDS. Tanzi says he is willing to license his discoveries to any company seeking to develop an ingredient of that cocktail. Toward that end, in 2000 he co-founded TorreyPines Therapeutics Inc. (TPTX ) in La Jolla, Calif., to work out a compound that lops off the amyloid fragment at the 38th molecule instead of the 42nd, rendering it harmless.

This year, Tanzi started work on his biggest project yet: identifying all the genes involved in Alzheimer's. He predicts he will have a genetic blueprint in hand within two years and a genetic test within five. Tanzi doesn't have to scrape around for cash this time, either. The Cure Alzheimer's Fund, founded by three Boston area families, pledged $3 million to his lab for this genetic detective work, stepping in where the NIA and venture capitalists refuse to tread.

PHARMA PARTNERS
In 2000, Wyeth CEO Robert Essner bucked a pharma industry trend and made Alzheimer's a research priority. It wasn't his idea. Essner, who came out of the marketing side of the business, was talked into a partnership with Elan Corp. (ELN ) by Wyeth scientists enthralled with the Irish company's vaccine for treating Alzheimer's, which they thought was the most promising treatment out there.

The scientists warned Essner it would take three years and $100 million just to get the treatment into human clinical trials. They also conceded that they couldn't even hazard a guess at the likelihood of success, the odds were so low. Essner took the leap anyway: "Our scientists were so passionate that if I had turned them down, I would have had a mutiny."

Five years on, Essner figures Wyeth has spent more than twice that estimated $100 million. He has also made the concept behind the vaccine—that the immune system can be primed to fight off amyloid—the centerpiece of Wyeth's Alzheimer's program.

In the spring of 2002, Elan and Wyeth scientists were immersed in clinical trials of the vaccine. But in March they were forced to halt the trials when 15 of 300 patients developed encephalitis, a dangerous swelling in the brain. A deep gloom spread through the Alzheimer's research community. The Elan-Wyeth drug was the first to "cure" the disease in mice, but the risk of encephalitis forced doctors to halt human tests.

The researchers didn't give up. When they examined the blood of several patients in the trial, they saw that the vaccine had produced antibodies against the amyloid, as it was meant to do. In the fall of 2003, the companies announced that the autopsied brains of four vaccine recipients who had died of other causes had no amyloid plaque. A few months later, Swiss doctors reported that 19 of 28 patients treated with the vaccine had produced antibodies against amyloid, and 12 of those 19 either improved or stabilized their performance on memory tests—the first proof of principle that clearing amyloid could alter the disease in people.

The vaccine, a safer version of which is now in early-stage trials, calls for a patient to be injected with a tiny piece of the A-beta 42 protein found in deadly plaque. The injected fragment prompts the body to produce antibodies, which seek out and destroy more of the offending A-beta molecules. But tampering with the immune system can stir up unfortunate side effects, such as encephalitis. It's safer to send in some handpicked soldiers instead, otherwise known as monoclonal antibodies. The Wyeth/Elan partnership created such a lab-built antibody to target the same molecule used in the vaccine experiments, A-beta 42.

When injected into a patient, the antibody locates and destroys amyloid fragments without activating the immune system. Data released last spring from the first human trial of the drug, called AAB-001, showed that patients performed significantly better on memory tests, and there was reduced plaque in autopsied brains. Results from an ongoing Phase 2 trial are expected in early 2007. If positive, the company is likely to move into final testing quickly, putting the drug on track for FDA review by 2010. Meanwhile, Wyeth's strategy has attracted the sincerest form of flattery: Eli Lilly, Pfizer, and now Genentech are all developing amyloid antibodies.

There are also dozens of startup companies with intriguing anti-amyloid drugs. "We've got 30 to 50 drugs in Phase 2 and eight or nine in Phase 3," says William Thies, the Alzheimer's Assn.'s vice-president for medical relations. "They've passed an awful lot of hurdles. I believe some will work, and we will keep developing better and better medicines."

SOLDIER WITH FORTUNE
Leonard Lauder, the 73-year-old chairman of Estee Lauder Cos. (EL ), is an elegant man with an elegant office. He works in a robin's-egg-blue room high up on Fifth Avenue with a to-die-for view of Central Park. Around his desk are artworks by Richard Serra, Agnes Martin, and Claes Oldenburg, and his large coffee table is covered with fashion magazines and lavish art books. All this beauty represents his "day job," as he puts it. In off hours, he is determined to find a cure for Alzheimer's. His reason is simple: "Name me one person who sooner or later doesn't worry about getting it."

Lauder is not content to use his fortune, estimated at $2.9 billion, to bolster long-standing Alzheimer's charities. In 1998 he and his younger brother, Ronald, founded the Institute for the Study of Aging solely to turn promising Alzheimer's research into commercial drugs. To date, the institute and an affiliated public charity have funded 167 projects, spending $25.5 million. "We figured that if we put enough money into it and backed enough ideas, we had a pretty good shot at coming up with a cure," says Lauder.

With the meager public funds available for Alzheimer's research, a scientist with a good idea must scramble for money. The Lauders' foundation aims to ease the burden. The two brothers knew how frustratingly slow the hunt has been for an Alzheimer's drug, and thought a venture philanthropy that focused on drug discovery rather than basic research might be able to close the gap between the two. They hired Dr. Howard Fillet, a renowned geriatrician who had treated their mother at Mount Sinai Medical Center in New York (Estee Lauder died of heart failure in 2004) and told him to forget about requiring complex grant proposals. "They gave me an office, a desk, and a pot of money," says Fillet, the institute's director. "I go to meetings, hear an interesting presentation, and tell the scientist, Call me. I'll give you money.'"

That's the story behind Allon Therapeutics Inc. ( NPC.TO ) in Vancouver. Some five years ago, Allon's founding scientist, Ilana Gozes of Tel Aviv University, had collected meager funds from friends and family to finance her research into a protein fragment necessary for brain formation. She had a hunch the fragment might shield neurons from the damage inflicted by Alzheimer's.

Gozes was just starting her company when Fillet learned about her work. Based on a few conversations, he handed her $350,000. "No one else would have made an investment at that point," says Allon CEO Gordon C. McCauley, who came on board in 2004 when his venture capital fund provided the next round of financing. Allon's treatment has since proven safe in people and is about to enter a larger trial. And Allon has enough capital to keep the trials going—the company went public in 2004.

JUST THE BEGINNING
Dr. Paul S. Aisen oversees the care of some 1,000 Alzheimer's patients as director of the Memory Disorders Program at Georgetown University School of Medicine, and there is little he can offer them. Consequently he is willing to test any reasonable-sounding experimental treatment that comes along, and his program is one of the nation's leading centers for Alzheimer's trials.

Unfortunately, clinical trials often turn into exercises in futility, since fewer than 10% of experimental drugs survive the three-stage process to win FDA approval. Aisen knows this all too well. He spent 15 years testing anti-inflammatories such as Aleve and Vioxx against Alzheimer's because studies seemed to show a link between the popular drugs and a lower incidence of the disease. But in 2003 he admitted defeat after a rigorous trial found that anti-inflammatories did no good. He published the results and moved on, searching for something else that would work. "It is the patients' plight that gives everyone on our team a great appreciation for the tremendous need for better treatments," says Aisen.

Today, Aisen is the lead investigator for Alzhemed. His clinic is also running trials on Flurizan, antibodies from Wyeth/Elan and Eli Lilly, and the generic anti-seizure medicine Valproate. But he'll look far afield from advanced biotech labs for treatments. That's why he is testing a drug derived from a Chinese moss that has been used for more than 2,000 years in the Middle Kingdom to treat fevers.

Aisen learned in 1999 that doctors in China had been using the drug, called Huperzine A, for some 20 years to relieve symptoms of Alzheimer's. Now made by Neuro-Hitech Inc. (NHPI ), the drug improves memory in much the same way as Pfizer's Aricept and other existing Alzheimer's treatments, without the gastrointestinal problems associated with these older drugs. But Aisen was most intrigued by evidence that, in mice, Huperzine A protected brain cells from the ravages of plaque and tangles, something the other drugs can't do.

Aisen is now in charge of a mid-stage trial of Huperzine A. But he does not expect it, or any of the drugs he is testing, to be the definitive cure the world craves. Ultimately, scientists and physicians say today's research is laying the groundwork for treatments that can prevent Alzheimer's from taking hold in the first place. "I'm hoping we'll put ourselves out of business in 20 years," says Dr. Reisa A. Sperling, head of Alzheimer's clinical trials at Brigham & Women's Hospital in Boston. "I'm 47, and before I retire, I believe I'll be looking for another disease to study."

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quelle: http://www.businessweek.com/magazine/content/07_02/b4016060.…

[tippse]

hier eine aktuelle firmenpräsentation:

http://www.neurochem.com/CorporatePresentation_November2006.…" target="_blank" rel="nofollow ugc noopener">http://www.neurochem.com/CorporatePresentation_November2006.…

[ollihat]

Antwort auf Beitrag Nr.: 26.631.019 von tippse am 01.01.07 23:41:19

Ich finde das sehr beruhigend, daß es bis dato keinen Thread für Neurochem gegeben hat. Alles, was hier im Übermaß auf WO besprochen wird, ist Schrott ( am einfachsten immer zu verfolgen unter der Rubrik Aktivste innerhalb der letzten 24 Stunden!).

Immerhin konnte man mit Neurochem in 2006 schon ganz schöne Gewinne machen. Wenn jetzt die Zeit der Entscheidung näher rückt, wird es heftige Kursbewegungen geben.

[tippse]

hier die beschreibung des seit juni 2004 in phase III befindlichen trials:

http://www.clinicaltrials.gov/ct/show/NCT00088673?amp;order=…

Primary Outcomes:

- The two primary efficacy parameters are the change from baseline to month 18 in the Alzheimer's Disease Assessment Scale, cognitive subpart (ADAS-cog)

- and the clinical Deterioration Scale Sum of Boxes (CDR-SB) scores.; The brain volume change from baseline as measured by Magnetic Resonance Imaging will also be assessed.


@olli: du hast natürlich recht - aber die tatsache, dass die meisten threads inhaltlich schrott sind, heißt ja noch lange nicht, dass man es nicht besser machen kann - deshalb sind beiträge in der sache gerne gesehen!

nebenbei: die kursentwicklung im vorfeld eines potenziellen approvals interessiert mich null (heißt, ich bin nicht investiert). hier ist man als kleinanleger nur der a...

wenn alzhemed zugelassen und von der medizinischen fachwelt anerkannt wird, reichen mir dann auch noch die letzten 100% - vorher ist mir das zu heiß - du weißt ja: "gier fressen hirn" (und das ist auch eine form von alzheimer

[ollihat]

Antwort auf Beitrag Nr.: 26.644.773 von tippse am 02.01.07 22:12:01

Warum gibst Du Dir dann so viel Mühe mit Neurochem, wenn Du nicht investiert bist?

Für die Investierten: heute konnte man 4% Plus machen;

Schlußkurs in Toronto 26 can $.

[BrauchGeld]

Antwort auf Beitrag Nr.: 26.631.019 von tippse am 01.01.07 23:41:19

""Alles, was hier im Übermaß auf WO besprochen wird, ist Schrott""

NRMX gehört wohl auch dazu ,die aktie ist einfach nur gnadenlos überbewertet mit fast 1 milliarde US$ marktkap., sollte Alzhemed scheitern wovon einige ausgehen sehe ich eine ähnlich performance wie Nuvelo (Nuvo) oder Telik (TELK).
Das wird wohl auch der grund sein warum es bisher keinen Thread gegeben hat .



http://www.marketwatch.com/News/Story/Story.aspx?guid=%7BEC0…

Then there's Neurochem (NRMX : neurochem inc com
News , chart, profile, more
Last: 21.47-0.57-2.59%

4:00pm 12/29/2006

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21.47, -0.57, -2.6%) , whose shares have leaped more than 40% over the past month -- tripling since August -- largely on anticipation for its Alzhemed Alzheimer's treatment, whose final round of test results are expected this spring. Founded in 1986, the Quebec-based company has nearly $200 million in accumulated losses, little in the way of revenue and a market value of $961 million. Noting the stock's recent rise, Toronto-based RBC Dominion Securities analyst Philippa Flint, who rates the stock an "underperform," told clients that "investors are assuming minimal risk of clinical development," when instead "we believe the risk is excessive and recommend investors take profits." Toronto-based Sprott Securities analyst David Dean went a step further, saying that "the trials are likely to fail."
Neurochem Chief Executive Officer Francesco Bellini acknowledges that the trials are "difficult" and that they "may fail." But he also says the patients in the current trial appear to be "doing well" and he wouldn't be an investor in the company if he didn't believe in the drug.
But even Mr. Bellini says investors in biotech should diversify. And what if the skeptics are wrong? "You have to always keep in mind, no matter how sexy the drug, no matter how bad you want prostate cancer cured -- in the end, you're not making a charitable donation," Mr. Miller reminds investors. "It's your investment capital, and you have to protect yourself by spreading it around." Just ask anybody who, sadly, bet it all on Northfield

[tippse]

der autor sieht aufgrund der vorgelegten phase III daten keinen signifikanten unterschied im fortschreiten der krankheit zwischen mit alzhemed behandelten patienten und "placebo-patienten". er sieht der veröffentlichung der endgültigen phase III ergebnisse skeptisch gegenüber
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Biotech
Neurochem's Risky Bet
By Adam Feuerstein
Senior Writer
1/22/2007 8:02 AM EST
URL: http://www.thestreet.com/newsanalysis/biotech/10333607.…

Canadian drugmaker Neurochem (NRMX) will soon put the leading scientific theory behind Alzheimer's disease to a major clinical test.

The theory -- dubbed the "beta-amyloid hypothesis" -- says that Alzheimer's is caused by protein plaques that accumulate in the brain, damaging and eventually killing nerve cells. These plaques consist of sticky protein fragments called beta-amyloid.

If a drug could be found that stops or slows the formation of beta-amyloid plaques -- or even clears them from the brain -- it might halt or even reverse the loss of memory and cognitive function that is the devastating mark of Alzheimer's.

That drug would be a super-blockbuster, easily generating billions of dollars in sales.

Neurochem believes it has the drug that fits the bill. The company's Alzhemed is being tested in two large, phase III clinical trials. The first of these trials, conducted in North America enrolling 1,052 patients with mild to moderate Alzheimer's, is complete and data should be released around April or May. (Neurochem shares closed Friday down 11 cents to $17.76.)

At the recent JPMorgan Healthcare Conference, Neurochem CEO Francesco Bellini showed off some blinded data from the phase III trial that he said indicated Alzhemed was working as planned.

During a breakout session with investors, Bellini said there was a lot of interest from potential partners for Alzhemed and that a deal might easily be made even before the phase III clinical data is released. (His latter comment seemed as much a show of confidence in Alzhemed as it was a dare to short-sellers to remain exposed to the stock.)

Well, I don't share Bellini's confidence, and I don't think you should either. I'm a data guy -- I like to see solid and ample evidence of a drug's efficacy before drinking the Kool-Aid. With Alzhemed, I don't believe we have either.

Let's go back to the phase II study that Neurochem ran to justify advancing Alzhemed into its pivotal phase III program. Results from that study were published in November in the medical journal Neurology.

Phase II studies are typically small in size; in fact they're rarely big enough, but in this case, Neurochem enrolled just 58 Alzheimer's patients, randomized to doses of 100, 200 and 300 milligrams of Alzhemed and a placebo arm.

After three months of treatment, there was no difference in cognitive function, memory performance or any other efficacy measure between the Alzhemed and placebo patients. On the other hand, the drug's safety profile was clean, and tests showed that the drug was getting into the central nervous system of patients and was reducing the levels of a biomarker for the beta-amyloid protein.

To be fair, three months of treatment doesn't allow much time for any Alzheimer's drug to show a clinical benefit. So Neurochem extended the study. All patients, including those previously on placebo, were invited to participate in an open-label, single-arm extension study using the 300 mg dose.

Efficacy, defined as a change in cognitive function, was assessed again at various time intervals. Because all patients in this extension study were on Alzhemed, there was no real control arm for comparison. Therefore, Neurochem decided to make comparisons using previously published data from other Alzheimer's disease trials in 1994. Efficacy was measured using the ADAS-cog test, a 0-to-70 scale of cognitive function.

The chart below summarizes some of the data from the phase II trial. In this case, smaller changes in the ADAS-cog score compared to baseline represents better outcomes for patients.

Alzhemed Phase II Open Label Extension Study 

Change in ADAS-cog Score from baseline 

 3 mos. 6 mos. 9 mos. 12 mos. 16 mos. 20 mos. 

Sample Size (mild/moderate AD patients) 42 41 34 30 26 24 

Mean change in ADAS-cog score 1.5 2.2 3.5 4.5 5.5 7.5 

Historical control (1994 data) n/a n/a 5.0 7.2 9.6 11.9 

Source: Company reports 

At first glance, it looks good for Alzhemed. All the patients are losing cognitive function over time, but patients on Alzhemed are progressing at a slower rate. At 20 months, for example, Alzhemed patients had a 7.5-point worsening of their cognitive ability based on the change in their ADAS-cog score, compared with an 11.9-point increase in the historical control group. (Remember, the higher the number, the worse for the patients.)

But there are problems with this data. The patient numbers are small; only 24 patients remained in the study at 20 months. This makes it hard to draw any good conclusions on Alzhemed's efficacy. The use of historical control data -- especially 12-year-old data -- also is dubious because Alzheimer's care has certainly improved since then.

But the biggest red flag, in my mind, is that these data are potentially biased because it excludes patients who were performing poorly on Alzhemed. Of the 42 patients who started the extension study, 18 -- or 43% -- had dropped out by 20 months.

But the dropped patients weren't included in the efficacy analysis. At least six of these dropped patients stopped taking Alzhemed because of "perceived lack of efficacy," according to the published report. Excluding these patients from the analysis likely makes Alzhemed appear more efficacious than it really is.

If it's hard to extract any confidence in Alzhemed from the phase II study, what about the ongoing phase III studies? Is there preliminary data there that might be used as a proxy to predict the study's final outcome?

Neurochem says such data do exist. The company has compiled blinded efficacy data combining patients on Alzhemed and placebo that it says point to an "encouraging trend" in favor of the drug,

The chart below is the data that Neurochem's Bellini showed investors at the JPMorgan conference. Like the chart above, smaller changes in the mean ADAS-cog score represent a slower loss of cognition and a better outcome for patients.

Blinded results from Phase III Alzhemed study

520 patients followed for 18 months

Mean change in ADAS-cog score from baseline 

 Blinded mild patients Blinded moderate patients 

 n=404  n=116  

improved/stable 41% -1.6 17% -1.3 

slow progression 23% 4.5 16% 4.4 

progression 36% 13.8 66% 15.8 

Source: Neurochem presentation Jan. 2007 

The takeaway point, from Neurochem CEO Bellini's perspective, was that a majority of the blinded patients with mild Alzheimer's (41%) continue to show improved or stabilized cognition after 18 months of treatment with Alzhemed. Since this data is blinded, Neurochem doesn't know which patients are on Alzhemed and which are taking a placebo, but the overall favorable trend suggests that the drug is having some positive effect, he says.

Again, I believe this analysis falls short. From the above chart, it's possible to calculate the weighted average of the blinded results for the mild and moderate groups.

Mild patients 5.3 point progression
Moderate patients 10.91 point progression
Weighted average for total 6.6 point progression

Examined this way, it's hard to be as confident with Alzhemed's performance, because the drug's blinded performance (a 5.3-point worsening of cognition on the ADAS-cog scale for mild patients) is comparable to placebo patient data in other recently conducted Alzheimer's drug trials.

An analysis of these studies, done by Sprott Securities analyst David Dean, showed that Alzheimer's patients given a placebo show about a 6-point progression on their ADAS-cog score over 18 months. (Dean has a reduce rating on Neurochem and his firm has no banking ties to the company.)

In others words, based on the data available, it's not clear what level of effect, if any, Alzhemed is having on patients with Alzheimer's. This makes the pending release of results from the Alzhemed phase III study a very high-risk event.

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Adam Feuerstein writes regularly for RealMoney.com. In keeping with TSC's editorial policy, he doesn't own or short individual stocks, although he owns stock in TheStreet.com. He also doesn't invest in hedge funds or other private investment partnerships. Feuerstein appreciates your feedback; click here to send him an email.

[Buddah]

sollte man noch rein?Meinungen?

[ollihat]

vielleicht kann man bei jetzt aufsteigenden Kursen bei 7$ mal was riskieren?

[goofey]

Antwort auf Beitrag Nr.: 29.655.257 von ollihat am 05.06.07 21:25:13

auf www.biospace.com wird heute mitgeteilt,daß Alzhemed keine Chance auf Zulassung haben wird

[SharpRatio]

Antwort auf Beitrag Nr.: 26.631.019 von tippse am 01.01.07 23:41:19

FDA Grants Neurochem Drug Special Status
Tuesday July 24, 8:55 am ET
FDA Grants Neurochem Alzheimer's Treatment 'Fast Track' Status for 6 Month Review

LAVAL (AP) -- Drug developer Neurochem Inc. said Tuesday government regulators granted its prospective Alzheimer's treatment special review status.

As a drug with "fast track" status, the Food and Drug Administration will attempt to review the company's Alzhemed in about 6 months, instead of the usual 10 months. FDA gives the special designation to drugs that address unmet medical needs.

Neurochem said it plans to meet with FDA next month to review its final-stage trials of the Alzheimer's treatment. The company said after reviewing North American trials of the drug, it is considering changing the structure of the European trial.

Shares of Neurochem Inc. rose 87 cents, or 14.8 percent, to $6.75 in premarket trading Tuesday, from their close Monday at $5.88.

[SharpRatio]

Antwort auf Beitrag Nr.: 26.631.019 von tippse am 01.01.07 23:41:19

So, dass dürfte für anständigen Upmove sorgen!

[stock_budgie]

Phase III - Boom...